Zero-Fluoroscopy Catheter Ablation of Right Appendage Focal Atrial Tachycardia in a Pregnant Woman.

BACKGROUND: Arrhythmias in pregnancy are complex to manage due to the teratogenic effects of many antiarrhythmic drugs and the common use of ionizing radiation during catheter ablation procedures. Furthermore, pregnant women are extremely vulnerable and difficult to treat because of the progressive physical and hormonal changes that occur during the nine months of pregnancy. CASE PRESENTATION: In this case report, we describe a complex clinical case of a 34-year-old pregnant woman who was affected by an incessant right atrial tachycardia, with signs and symptoms of initial hemodynamic instability. This tachycardia was refractory to antiarrhythmic drugs, so a zero-fluoroscopy ablation was performed. The first procedure was complicated by cardiac tamponade, quickly resolved without further complications for the mother or the fetus. In the following days, a deep venous thrombosis occurred at the femoral venous access. After a few days, the patient underwent a second procedure that was successful and resulted in the restoration of a sinus rhythm. CONCLUSIONS: The management of this clinical case was complex both from a procedural and a clinical (cardiological and gynecological) point of view. Finally, the integration of the various skills led to an excellent result.

Transcatheter closure of atrial septal defect using intracardiac echocardiography: a two-center, retrospective study.

AIMS: We present the experience and long-term results of intracardiac echocardiography (ICE)-guided closure of ostium secundum atrial septal defects (ASDs) in two Italian centers and investigate its systematic applicability as the gold standard in routine clinical practice. METHODS: We retrospectively evaluated all consecutive patients who underwent an ASD percutaneous closure procedure from March 2008 to February 2020. All patients underwent a preprocedural transesophageal echocardiography (TEE) evaluation. The closures were carried out under fluoroscopic and ICE guidance. A follow-up visit was performed at 1, 3 and 12 months, followed by telephone evaluations approximately every 2 years. RESULTS: Sixty-six patients (29% male individuals), mean age 43 ±â€Š16 years, were treated. In 15 cases, the TEE defect diameter was less than 10 mm, and in 8 of these patients, the ICE intraprocedural sizing increased the maximum diameter by more than 5 mm. Sizing balloon of the defect was performed in 51 cases; 2 patients received an ASD 38 mm device. Eight patients had multiple defects; in three of these, it was necessary to apply two devices. Four patients showed nonsignificant residual shunt; no complications related to the use of ICE were observed. One patient presented the migration of the ASD device into the abdominal aorta, percutaneously retrieved with a snare. No major complications were recorded during the entire follow-up period. CONCLUSION: This study confirms that ICE monitoring during ASD percutaneous closure is well tolerated and effective; it might be achievable as a routine gold standard by operators willing to use ICE systematically in all transcatheter closure interventions of interatrial communications.

Zero Fluoroscopy Arrhythmias Catheter Ablation: A Trend Toward More Frequent Practice in a High-Volume Center.

Background: Awareness of radiation exposure risks associated to interventional cardiology procedures is growing. The availability of new technologies in electrophysiology laboratories has reduced fluoroscopy usage during arrhythmias ablations. The aim of this study was to describe procedures with and without X-Rays and to assess feasibility, safety, and short-term efficacy of zero fluoroscopy intervention in a high-volume center oriented to keep exposure to ionizing radiation as low as reasonably achievable. Methods: Cardiac catheter ablations performed in our hospital since January 2017 to June 2021. Results: A total of 1,853 procedures were performed with 1,957 arrhythmias treated. Rate of fluoroless procedures was 15.4% (285 interventions) with an increasing trend from 8.5% in 2017 to 22.9% of first semester 2021. The most frequent arrhythmia treated was atrial fibrillation (646; 3.6% fluoroless) followed by atrioventricular nodal reentrant tachycardia (644; 16.9% fluoroless), atrial flutter (215; 8.8% fluoroless), ventricular tachycardia (178; 17.4% fluoroless), premature ventricular contraction (162; 48.1% fluoroless), and accessory pathways (112; 31.3% fluoroless). Although characteristics of patients and operative details were heterogeneous among treated arrhythmias, use of fluoroscopy did not influence procedure duration. Moreover, feasibility and efficacy were 100% in fluoroless ablations while the rate of major complications was very low and no different with or without fluoroscopy (0.45 vs. 0.35%). Conclusion: Limiting the use of X-Rays is necessary, especially when the available technologies allow a zero-use approach. A lower radiation exposure may be reached, reducing fluoroscopy usage whenever possible during cardiac ablation procedures with high safety, full feasibility, and efficacy.

Effect of hepatitis C antiviral therapy on oral lichen planus and hyposalivation in inmates.

BACKGROUND: Oral lichen planus (OLP) and hyposalivation have been reported as extrahepatic manifestations of hepatitis C virus (HCV) infection. Our study evaluated the effect of direct antiviral agents (DAAs) on OLP and hyposalivation in convicts with chronic hepatitis C, examining patients before, during and after the antiviral treatment period with direct acting antiviral agents (DAAs). METHODS: We screened 198 inmates for the presence of the HCV antibody. Patients found to be positive underwent a quantitative HCV-RNA test and HCV genotype typing, as well as an oral cavity examination using a scoring system for OLP (REU score) and the clinical oral dryness score (CODS). Subsequently, all patients underwent DAA therapy and a systematic physical examination of the oral cavity at 1, 3 and 6 months from the beginning of treatment. RESULTS: Fifty patients (25.25%) had a positive HCV-RNA test. At baseline, OLP was detected in 4 patients (8%), with a mean REU score of 10.13±4, and different degrees of hyposalivation were seen in 17 patients (34%), with a mean CODS score of 4.71±1.72. Six months after the start of DAA therapy, we observed resolution of OLP in 3 patients (75%) and improvement in the remaining subject with a significantly lower mean REU score (2±4). Hyposalivation disappeared in 5 patients, improved in 10, and remained unchanged in 2 patients with a significantly lower mean CODS score (0.06±0.24). CONCLUSION: This study demonstrated the effectiveness of DAAs in the treatment of OLP and hyposalivation.

ECMO-Supported Ablation and Percutaneous Repair of Severe Valvulopathy: A Winning Combination in a Complex Clinical Case.

In this case report, we describe a complex case of a 67-year-old patient who was suffering from acute heart failure with electrical storm. Clinical case management was based on an integrated approach comprising two different procedures that were complementary and synergistic, and that allowed the patient to reach acute stabilization and to demonstrate mid-term clinical improvement. Complex clinical settings, such as electrical and hemodynamic instability, require complex solutions. The use of an integrated approach that allows physiopathological mechanisms to work together may be beneficial for these patients.

Cardiopulmonary Support During Catheter Ablation of Ventricular Arrhythmias With Hemodynamic Instability: The Role of Inducibility.

Background: Catheter ablation is a treatment option for sustained ventricular tachycardias (VTs) that are refractory to pharmacological treatment; however, patients with fast VT and electrical storm (ES) are at risk for cardiogenic shock. We report our experience using cardiopulmonary support with extracorporeal membrane oxygenation (ECMO) during catheter ablation of VT. Methods: Sixty-two patients (mean age 68 ± 9 years; 94% male) were referred to our center for catheter ablation of repeated episodes of hemodynamically unstable ventricular arrhythmias. ES was defined as the occurrence of three or more VT/ventricular fibrillation episodes requiring electrical cardioversion or defibrillation in a 24-h period. All patients had hemodynamically unstable VTs. Results: Thirty-one patients (group 1) performed catheter ablation without ECMO support and 31 patients (group 2) with ECMO support. At the end of the procedure, ventricular inducibility was not performed in 16 patients of group 1 (52%) due to significant hemodynamic instability. Ventricular inducibility was performed in the other 15 patients (48%); polymorphic VTs were inducible in eight patients. In group 2, VTs were not inducible in 29 patients (93%); polymorphic VTs were inducible in two patients. The median follow-up duration was 24 months. Four patients of group 1 (13%) and five patients of group 2 (16%) died due to refractory heart failure. An implantable cardioverter-defibrillator intervention (shock or antitachycardia pacing) was documented in 13 patients of group 1 (42%) and six patients of group 2 (19%). Conclusions: Extracorporeal membrane oxygenation support during catheter ablation for hemodynamically unstable VTs is a useful tool to prevent acute procedural heart failure and to reduce arrhythmic burden.

HCV testing and treatment initiation in an Italian prison setting: A step-by-step model to micro-eliminate hepatitis C.

BACKGROUND: HCV infection among vulnerable populations is currently a major issue for HCV elimination program. Incarcerated people and people who inject drugs (PWIDs) are key population groups potentially at high risk for HCV infection. Our aim was to evaluate an extended program of screening, staging and treatment in Italian prison settings. METHODS: Patients from eight prisons in five different Italian Regions were enrolled. HCV saliva test (QuickOral Test®) was offered. Data on infection awareness and illicit drug use were also collected. Positive patients underwent early HCV RNA evaluation, staging and prescription on DAAs treatment. The definition of PWID was based on self-reported injecting drug use extracted from medical records (injecting drug use during the previous six months). RESULTS: A total of 2,376 out of 2,687 individuals (88%) was tested. The median (IQR) age was 42 (32-50) years. PWIDs were 537out of 2,376 (23%). Prevalence of HCV antibodies was 10.4% (248/2,376). PWIDs had a lower awareness of their HCV-Ab positivity than non-PWIDs (p-value <0.001). Furthermore, PWIDs were less likely to be previously treated than non-PWIDs (78% vs 96%, p-value= 0.017). Active infection was found in 41% of patients (101/248). Overall, 61% HCV-positive were PWIDs, with 44% HCV RNA positive. HCV therapy was prescribed to 83% (84/101) of patients with active HCV infection and 67% of these (56/84) were PWIDs. Prescription for HCV treatment in PWIDs accounted for 84% (56/67) (while for non-PWIDs was 82% (28/34) p-value: 0.88. Seventeen patients were referred to a Specialist in other prisons because they were going to be transferred soon to another prison. EOT, as well as SVR12 were achieved in 98% (82/84) treated patients. CONCLUSIONS: Among patients, PWIDs had a lower awareness of their HCV-Ab positivity and had previously received less treatments. Saliva test allowed to achieve a more rapid result, stage, and treatment approach. More than 80% of patients underwent treatment, without differences between PWIDs and non-PWIDs. Linkage to care during prison transfer allowed to avoid unplanned interruptions and offered more chances to reach the end of treatment.

COVID-19 Risk Management and Screening in the Penitentiary Facilities of the Salerno Province in Southern Italy.

(1) Background: The emergency linked to the spread of COVID-19 in Italy has led to inevitable consequences on the penitentiary system. The risks of this emergency in prisons is mainly related to the problem of persistent overcrowding that makes social distancing difficult and the isolation of any contagion hard to arrange. The Department of Protection for Adults and Minors of the ASL Salerno Criminal Area has taken steps in order to perform screening operations and minimize the risks for prisoners and operators. (2) Methods: We conducted a two-phase observational study. In the first phase, we offered and then executed serum COVID-19 screening to all the convicted inmates. For those who had a doubtful or positive result, a swab was executed in the shortest time possible. In the second phase, a pharyngeal swab was offered and executed to all the police officers, the penitentiary administrative staff and the medical personnel working in the prison. (3) Results: In the first phase, we executed 485 COVID-19 blood tests on prisoners, 3 (0.61%) of which were positive. The three positive inmates underwent nasopharyngeal swabbing, which ultimately were negative. After that, we executed 276 nasopharyngeal swabs on the prison personnel, penitentiary administrative staff and medical personnel-all were negative. (4) Conclusion: All tests (blood tests and swabs) that were carried out on the prisoners and on the staff were negative for COVID-19. We believe that all prisons in Italy and in the world should take action to ensure preventive and control measures in order to safeguard the health of the prison population and of all the people who work there.

Electroanatomic guidance versus conventional fluoroscopy during transseptal puncture for atrial fibrillation ablation.

INTRODUCTION: Technological advancement in the setting of atrial fibrillation (AF) ablation has decreased radiation exposure and complications associated with the procedure. Yet, transseptal puncture (TSP) remains a challenging step that necessitates accurate guidance. We describe our experience performing TSP under electroanatomic (EA) guidance. METHODS AND RESULTS: The analysis included 145 consecutive EA-guided ablation procedures performed between June 2018 and April 2019 and 145 consecutive standard ablations performed before June 2018. EA guidance utilized the CARTO 3 three-dimensional mapping system to reconstruct anatomic and electrical characteristics of the right atrium and fossa ovalis. Patients with a history of previous cardiac surgery were excluded. For EA-guided procedures, the mean patient age was 60 ± 10 years, 75.2% were male, and 69.0% had paroxysmal AF. Similarly, the mean age for conventional procedures was 60 ± 11 years, 71.0% were male, and 71.7% had paroxysmal AF. The fossa ovalis was detected as a region of low voltage, <0.75 mV. EA guidance yielded shorter fluoroscopy times (EA vs. conventional, 3.6 ± 2.5 vs. 13.5 ± 10.5 min; p < .001) and a lower dose area product than conventional guidance (13 ± 11 Gy* cm2 vs. 28 ± 27 Gy* cm2 ; p < .001). The total procedure duration was similar between groups (146 ± 48 vs. 148 ± 54 min). There were no significant complications related to TSP. CONCLUSION: During AF ablation, TSP with EA guidance facilitated safe access to the left atrium while reducing radiation risk to both patients and operators.

Hepatitis C virus infection in jail: Difficult-to-reach, not to-treat. Results of a point-of-care screening and treatment program.

BACKGROUND: An unmet objective in the pursuit of HCV elimination is the creation of a simple and fast operating model to identify difficult-to-treat populations, like prisoners. Of many obstacles, the first is represented by the poor knowledge of inmates HCV-Ab prevalence. Moreover, due to the peculiar status of conviction, often their access to antiviral therapy is neglected. AIMS: To evaluate the prevalence of HCV infection in a penitentiary Institution of Southern Italy through a point-of-care screening and treatment program. METHODS: We conducted a prospective observational study in two phases: first, we reviewed all the prisoners' clinical records, to verify HCV-Ab execution. Subsequently, we performed a universal point-of-care screening and treatment program. RESULTS: We enrolled 670 patients. Overall, 310(46.27%) were already HCV-Ab tested. At the screening initiation, 23.28% patients were discharged, whereas 8.35% refused. Of the remaining 458 subjects, 58(12.67%) were HCV-Ab positive and 46 HCVRNA positive. All these underwent DAA, obtaining 100% SVR. At the end of the program, a total of 491(73.28%) subjects had HCV-Ab available. Sixty-nine (14.05%) were positive. A total of 214(31.94%) subjects were lost to follow-up. CONCLUSIONS: We revealed a prevalence of 14.05% of HCV-Ab in conviction. Antiviral treatment was safe and efficacious. More efforts are advisable to provide screening for HCV-Ab in conviction.

Cardiopulmonary support in patients undergoing catheter ablation of poorly tolerated ventricular arrhythmias and electrical storm.

INTRODUCTION: Catheter ablation is an important treatment option for sustained ventricular arrhythmias (VA) that are refractory to pharmacological treatment; however, patients with fast VA or electrical storm (ES) are at risk for cardiogenic shock. We report our experience using cardiopulmonary support with extracorporeal membrane oxygenation (ECMO) during catheter ablation of VA. METHODS: Nineteen patients (mean age, 62 ± 10 years; 84% male) were referred to our center for CA of ES between January 2017 and April 2018. ES was defined as the occurrence of ≥3 ventricular tachycardia or ventricular fibrillation episodes requiring electrical cardioversion or defibrillation in a 24-hour period. ECMO support was implemented for all patients. RESULTS: CA of ES was completed in all patients. Activation mapping was performed for all VTs and substrate modification was performed by targeting sites identified by late/fragmented abnormal potentials. VTs were not inducible after ablation in 16 of 19 patients (84%). With regard to procedural complications, two patients underwent percutaneous angioplasty with stenting for a femoral artery dissection and one patient was treated for a dislodged ECMO arterial cannula and subsequent hemorrhagic shock. After a median follow-up of 10 months, three patients died from refractory heart failure and one patient died as a result of ES. Overall, the procedural success rate was 68% and the Kaplan-Meier mortality rate was 21%. CONCLUSIONS: ECMO support may be used for ablation procedures in patients with ES.

Efficacy and safety of new direct antiviral agents in hepatitis C virus-infected patients with diffuse large B-cell non-Hodgkin's lymphoma.

The association of hepatitis C virus (HCV) with non-Hodgkin's lymphoma (NHL) has been demonstrated throughout the world. The new interferon-free direct antiviral agents (DAAs) showed high efficacy and safety, and preliminary data seem to confirm their activity on low-grade NHL. The question arises as whether or not-and how-to treat the HCV-positive patients suffering from diffuse large B-cell lymphomas (DLBCLs). The aim of this observational study was to evaluate whether DAA antiviral treatment of DLBCL/HCV-infected patients in concomitance with chemotherapy is a safe and effective option. Twenty (13 males and 7 females) HCV genotype 1b-positive subjects, undergoing chemotherapy for DLBCL, were enrolled between June 2015 and December 2015. After informed consent, all patients underwent antiviral therapy (AVT) with sofosbuvir/ledipasvir and chemotherapy (14 rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone and 6 cyclophosphamide, doxorubicin, vincristine, and prednisone) for DLBCL. Complete hematological (Revised European-American Lymphoma classification, Ann Arbor, and International Prognostic Index [IPI] scores) and hepatological (viral markers, liver stiffness, and biochemical parameters) evaluations were made. A historical retrospective cohort of 101 DLBCL/HCV-positive patients not undergoing AVT was enrolled for comparison. DAA-treated and untreated patients were similar for sex distribution, IPI score, and NHL stage, and differed for age (older in treated), chemotherapy and use of AVT. Overall survival (OS) and disease-free survival (DFS) were evaluated among a 52-week of follow-up. No statistical difference was found in OS after 52 weeks (P = 0.122), whereas a statistically significant higher DFS was achieved in treated patients (P = 0.036). At the multivariate analysis, only IPI score and AVT were independently correlated with a better DFS. No differences in adverse events were reported. CONCLUSION: DAA treatment in concomitance with chemotherapy was shown to be safe and effective in influencing remission of aggressive lymphomas in HCV patients. (Hepatology 2018;67:48-55).

Liver biopsy in type 2 diabetes mellitus: Steatohepatitis represents the sole feature of liver damage.

Recent studies report a prevalence of non-alcoholic fatty liver disease (NAFLD) of between 70% and 80% in patients with metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Nevertheless, it is not possible to differentiate between simple steatosis and non-alcoholic steatohepatitis (NASH) with non-invasive tests. The aim of this study was to differentiate between simple steatosis and NASH by liver biopsy in patients with hypertransaminasemia and MS or T2DM. Two hundred and fifteen patients with increased ALT levels and MS, and 136 patients at their first diagnosis of T2DM regardless of ALT values were consecutively admitted to a tertiary hepatology center between January 2004 and November 2014. Exclusion criteria were other causes of liver disease/ALT increase. Each patient underwent a clinical, laboratory and ultrasound evaluation, and a liver biopsy. Gender distribution, age, and body mass index were similar in the two groups of patients, whereas cholesterol levels, glycemia and blood pressure were significantly different between the two groups. The prevalence of NAFLD was 94.82% in MS patients and 100% in T2DM patients. NASH was present in 58.52% of MS patients and 96.82% of T2DM. Consequently, this study reveals that, by using liver biopsy, almost all patients with T2DM or MS have NAFLD, which in patients with T2DM means NASH. Importantly, it suggests that NASH may be one of the early complications of T2DM due to its pathophysiological correlation with insulin resistance.

Effects of Levosimendan on Endothelial Function and Hemodynamics During Weaning From Veno-Arterial Extracorporeal Life Support.

OBJECTIVE: Weaning from veno-arterial extracorporeal life support is challenging. The objective of this trial was to investigate the endothelial and hemodynamic effects of levosimendan in cardiogenic shock patients supported with veno-arterial extracorporeal life support. DESIGN: This was a prospective observational trial. SETTING: Cardiovascular intensive care unit of a large tertiary care university hospital in Monza, Italy. PARTICIPANTS AND INTERVENTIONS: Flow-mediated dilatation of the brachial artery and hemodynamic parameters were assessed in 10 cardiogenic shock patients supported with veno-arterial extracorporeal life support, before and after the infusion of levosimendan. MEASUREMENTS AND RESULTS: Flow-mediated dilatation increased both as absolute value and as a percentage after levosimendan, from 0.10±0.12 to 0.61±0.21 mm (p<0.001) and from 3.2±4.2% to 17.8±10.4% (p<0.001), respectively. Cardiac index increased from 1.93±0.83 to 2.64±0.97 L/min/m2 (p = 0.008) while mixed venous oxygen saturation increased from 66.0% to 71.5% (p = 0.006) and arterial lactate levels decreased from 1.25 to 1.05 mmol/L (p = 0.004) without significant variations in arterial oxygen saturation or hemoglobin levels. This made it possible for clinicians to reduce extracorporeal membrane oxygenation blood flow from 1.92±0.65 to 1.12±0.49 L/min/m2 (p<0.001). CONCLUSION: In conclusion, in the authors' study population of adult cardiogenic shock patients supported with veno-arterial extracorporeal life support, their observations supported the use of levosimendan to improve endothelial function and hemodynamics and facilitate weaning from the extracorporeal support.

Implantation of the Jarvik 2000® left ventricular assist device using the miniaturized extracorporeal circulation system - a case report.

Myocardial failure is generally considered to be a progressive, irreversible medical condition with characteristic ventricular enlargement, spatial alteration of the heart chambers, diminished cardiac inotropy and resultant dysfunctional, mechanically inefficient heart.The Jarvik 2000®, similar to the mechanical pump, is an electrically powered, axial-flow left ventricular assist device (LVAD) designed to enhance the function of the chronically failing heart and, consequently, normalize the cardiac output for a long period of time.We report the case of 70-year-old man with congestive dilated cardiomyopathy and bioprosthetic mitral valve who underwent surgical implantation of the Jarvik 2000® LVAD, using the miniaturized extracorporeal circulation (MECC) system.The LVAD was implanted through a left thoracotomy and the MECC system was used to avoid intraoperative spontaneous hemodynamic instability and/or malignant ventricular arrhythmia. The circulatory support with the MECC system was optimal and no complication in terms of hemodynamic instability and perioperative bleeding was recorded. The MECC system obliterated the adverse effects associated with conventional extracorporeal circulation, which are often fatal in critically-ill patients.

Assessing Endothelial Responsiveness After Cardiopulmonary Bypass: Insights on Different Perfusion Modalities.

OBJECTIVE: Cardiopulmonary bypass (CPB) exerts several deleterious effects on inflammatory pathways. Most of these can be related to an endothelial insult leading to endothelial dysfunction. To date, the degree of endothelial damage only has been evaluated on a cellular and molecular level, but no studies exist looking at the functional effects of CPB on the endothelium. DESIGN: Previous studies hypothesized a negative effect of continuous flow as opposed to the physiologic pulsatile flow. The aim of the present retrospective study was to investigate how different perfusion modalities during CPB (ie, continuous v pulsatile flow) or its avoidance differently impact endothelial function. SETTING: Cardiovascular operating room and intensive care unit of a large tertiary University Hospital in Monza, Italy. PARTICIPANTS: Flow-mediated dilatation (FMD) of the brachial artery was assessed in 29 patients undergoing elective myocardial revascularization. Ten patients receiving continuous-flow CPB, 10 receiving pulsatile-flow CPB, and 9 scheduled for beating-heart revascularization were studied. INTERVENTIONS: Patients were studied at baseline (after induction of general anesthesia), after CPB upon intensive care unit (ICU) admission after surgery, and on the first postoperative day before discharge from the ICU (on average, 24 hours after CPB discontinuation). MEASUREMENTS AND MAIN RESULTS: The continuous-flow CPB group demonstrated a significant reduction in FMD after CPB, (12.8% ± 9.7% v 1.6% ± 1.5%, p<0.01), which lasted up to the first postoperative day (5.9% ± 4.1%). On the other hand, FMD did not change in the pulsatile-flow group (12.5% ± 10.5%, 11.0% ± 7.2%, and 16.6% ± 11.7%, respectively). FMD also was unaffected in the beating-heart group, thus suggesting a direct effect of CPB itself on endothelial function. CONCLUSIONS: In conclusion, in this study population of adult patients undergoing elective coronary revascularization, continuous-flow CPB markedly impaired endothelial function, although this was not the case with pulsatile-flow CPB. This study posed the rationale for further investigations on the potential value of FMD to predict cardiovascular events in these patients.

Systemic and myocardial inflammatory response in coronary artery bypass graft surgery with miniaturized extracorporeal circulation: differences with a standard circuit and off-pump technique in a randomized clinical trial.

Inflammatory response and hemodilution are the main drawbacks of extracorporeal circulation. We hypothesize that the use of miniaturized extracorporeal circulation (MECC) might lower the systemic and myocardial inflammatory patterns compared with a standard system (SECC) and off-pump coronary artery bypass grafting (OPCABG). Sixty-one patients undergoing isolated coronary artery bypass graft were prospectively randomized to MECC (n = 19), SECC (n = 20), or OPCABG (n = 22). Blood samples were collected from radial artery and coronary sinus to analyze blood lactate, hemodilution, and markers for inflammation and endothelial activation such as tumor necrosis factor (TNF)-α, interleukin-6, monocyte chemotactic protein-1, and E-selectin. No differences were observed in early clinical outcome. Interleukin -6 levels increased in every group during and after cardiac surgery, whereas TNF-α values grew in the SECC group (p = 0.05). E-selectin systemic values decreased during and after operation (p = 0.001) in every group. Monocyte chemotactic protein-1 systemic and cardiac levels raised only in SECC group (p = 0.014). In conclusion, MECC is comparable to SECC and OPCABG in the clinical outcome of low-risk patients, and it might be extensively used with no additional intraoperative risk. The analysis of the inflammatory patterns of endothelial activation shows MECC as effective as OPCABG, suggesting further studies to clarify MECC recommendation in high-risk patients.

Favourable survival of in-hospital compared to out-of-hospital refractory cardiac arrest patients treated with extracorporeal membrane oxygenation: an Italian tertiary care centre experience.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) support has been suggested to improve the survival rate in patients with refractory in- and out-of-hospital cardiac arrest (IHCA and OHCA). The aim of our study is to report our experience with ECMO in these patients. DESIGN: Retrospective, single-centre, observational study. PATIENTS: From January 2006 to February 2011 we studied 42 patients (31 males) with refractory cardiac arrest. MEASUREMENT AND MAIN RESULTS: ECMO implantation was successful in 38 (90%) of the 42 patients. ECMO support was positioned: three times (8%) in the operating room, six (16%) in the cardiac surgery intensive care unit, 21 (55%) in the emergency room, five (13%) in the catheterisation laboratory and three (8%) in the general ward. A total of 14 IHCA (58%) and three OHCA (16%) patients were weaned from ECMO (p<0.05). Eleven IHCA (46%) and one OHCA (5%, p<0.05) patients were discharged from intensive care unit (ICU). Among IHCA patients, 10 were alive at 6 months, nine of whom (38%) with good neurological outcome. Among OHCA patients weaned from ECMO, one was alive at 6 months with good neurological outcome (5%, p<0.05 vs. IHCA). CONCLUSIONS: ECMO support should be considered as a resuscitation alternative in selected patients. More specifically, patients with witnessed IHCA benefit more from ECMO treatment compared to those who experience an out-of-hospital cardiac arrest.

Mutations in FN1 cause glomerulopathy with fibronectin deposits.

Glomerulopathy with fibronectin (FN) deposits (GFND) is an autosomal dominant disease with age-related penetrance, characterized by proteinuria, microscopic hematuria, hypertension, and massive glomerular deposits of FN that lead to end-stage renal failure. The genetic abnormality underlying GFND was still unknown. We hypothesized that mutations in FN1, which encodes FN, were the cause of GFND. In a large Italian pedigree with eight affected subjects, we found linkage with GFND at the FN1 locus at 2q32. We sequenced the FN1 in 15 unrelated pedigrees and found three heterozygous missense mutations, the W1925R, L1974R, and Y973C, that cosegregated with the disease in six pedigrees. The mutations affected two domains of FN (Hep-II domain for the W1925R and the L1974R, and Hep-III domain for the Y973C) that play key roles in FN-cell interaction and in FN fibrillogenesis. Mutant recombinant Hep-II fragments were expressed, and functional studies revealed a lower binding to heparin and to endothelial cells and podocytes compared with wild-type Hep-II and an impaired capability to induce endothelial cell spreading and cytoskeletal reorganization. Overall dominant mutations in FN1 accounted for 40% of cases of GFND in our study group. These findings may help understanding the pathogenesis of proteinuria and glomerular FN deposits in GFND and possibly in more common renal diseases such as diabetic nephropathy, IgA nephropathy, and lupus nephritis. To our knowledge no FN1 mutation causing a human disease was previously reported.