Long-term incidence of arrhythmias in extracardiac conduit Fontan and comparison between systemic left and right ventricle.

AIMS: The extracardiac conduit-Fontan (ECC) has become the preferred technique for univentricular heart palliation, but there are currently no data on the incidence of long-term arrhythmias. This study investigated the incidence of arrhythmias and relation to single ventricle morphology in the long-term follow-up (FU) in ECC. METHODS AND RESULTS: All patients with ECC performed in our Centre between 1987 and 2017 were included (minimum FU 5 years). Of 353 consecutive patients, 303 [57.8% males, aging 8-50 (median 20) years at last FU] were considered and divided into two groups depending on left (194 in Group 1) or right (109 in Group 2) ventricular morphology. Eighty-five (28%) experienced ≥1 arrhythmic complications, with early and late arrhythmias in 17 (5.6%) and 73 (24.1%) patients, respectively. Notably, late bradyarrhythmias occurred after 6 years in 21 (11%) patients in Group 1, and in 15 (13.8%) in Group 2 [P = 0.48]. Late tachyarrhythmias occurred in 55 (18.2%) patients after 12 years: 33 (17%) in Group 1 and 22 (20.2%) patients in Group 2 [P  = 0.5]. Ventricular tachycardias (VT) were documented after 12.5 years in 14 (7.2%) patients of Group 1 and 15 (13.8%) of Group 2 [P = 0.06] with a higher incidence in Group 2 during the FU [P = 0.005]. CONCLUSION: Extracardiac conduit is related to a significant arrhythmic risk in the long-term FU, higher than previously reported. Bradyarrhythmias occur earlier but are less frequent than tachyarrhythmias. Interestingly, patients with systemic right ventricle have a significantly higher incidence of VT, especially in a very long FU.

Autosomal Recessive Long QT Syndrome: Clinical Aspects and Therapy.

The autosomal recessive (AR) form of Long QT Syndrome (LQTS) is described both associated with deafness known as Jervell and Lange-Nielsen (JLN) syndrome, and without deafness (WD). The aim of the study is to report the characteristics of AR LQTS patients and the efficacy of the therapy. Data of all children with AR LQTS referred to the Bambino Gesù Children's Hospital IRCCS from September 2012 to September 2021were included. Three (30%) patients had compound heterozygosity and 7 (70%) had homozygous variants of the KCNQ1 gene, the latter showing deafness. Four patients (40%) presented aborted sudden cardiac death (aSCD): three with previous episodes of syncope (75%), the other without previous symptoms (16.6% of asymptomatic patients). An episode of aSCD occurred in 2/3 (66.7%) of WD and heterozygous patients, while in 2/7 (28%) JLN and homozygous patients and in 2/2 patients with QTC > 600 ms. All patients were treated with Nadolol. In 5 Mexiletine was added, shortening QTc and obtaining the disappearance of the T-wave alternance (TWA) in 3/3. Episodes of aSCD seem to be more frequent in LQTS patients with compound heterozygous variants and WD than in those with JLN and homozygous variants. Episodes of aSCD also appear more frequent in children with syncope or with QTc value > 600 ms, even on beta-blocker therapy, than in patients without syncope or with Qtc < 600 ms. However, our descriptive results should be confirmed by larger studies. Moreover, Mexiletine addition reduced QTc value and eliminated TWA.

A decade of insertable cardiac monitors with remote monitoring in pediatric patients.

BACKGROUND: Remote monitoring-enabled insertable cardiac monitors (ICMs) are useful tools for arrhythmias and symptom management. This study sought to evaluate the outcome of ICM implantation in a large, heterogeneous cohort of pediatric and young adult patients. METHODS: Single centre, retrospective analysis of patients who underwent ICM implantation in 2010-2019. Patients were analysed according to age, symptoms, arrhythmias and underlying heart disease. RESULTS: A total of 200 consecutive patients (58% male), aged 11.5 ± 5.8 years at ICM implantation, were included. Follow-up was 31 ± 18 months. Electrophysiologic study (EPS) was initially performed in 123 patients and was negative in 85%. Patients had no heart disease (57.5%), congenital heart defects (21%), channelopathies (14.5%), cardiomyopathies/heart tumors (8%). The commonest symptoms were syncope/presyncope (45.5%) and palpitations (12.5%). A definite diagnosis was made in 63% of patients (positive diagnosis in 25%, negative in 38%) after 8 (2-19) months of monitoring. EPS results and the presence/absence of an arrhythmia before ICM implantation had no impact on the diagnostic yield. Symptomatic patients as well as patients without structural heart disease showed higher diagnostic yield. Patients with a positive diagnosis underwent pacemaker/implantable cardioverter-defibrillator implantation (13%), pharmacological treatment (10.5%), or catheter ablation (1.5%). CONCLUSIONS: In a large cohort of 200 children and young adults, ICMs with remote monitoring showed a high diagnostic yield (63%), especially in symptomatic patients and in patients without structural heart disease.

DOG-1 positive primary acinic cell carcinoma of the lung and investigation of molecular status.

Primary acinic cell carcinoma (ACC) of the lung is an extremely rare neoplasm that more often arises near to a right bronchus. It is characterized by two populations of clear and dark eosinophilic cells, arranged in a glandular acinar pattern. Mitosis are rare and tumor cells show small and eccentric nuclei. Positive stain for PAS, PAS-D, cytokeratin, A1AT and A1ACT is reported, while TTF1, p40, synaptophysin, SMA, and S100 are substantially negative. DOG-1 positive stain was observed in ACC of the salivary glands and its negativity was proposed to distinguish between primary and metastatic ACC of the lung. Here, we report the 30th case of primary ACC of the lung, describing the immunohistochemical positivity for DOG-1 and the molecular status of the neoplasm for the first time.

Progressive involvement of cardiac conduction system in paediatric patients with Kearns-Sayre syndrome: how to predict occurrence of complete heart block and sudden cardiac death?

AIMS: The aims of this study are to evaluate the progressive involvement of the cardiac conduction system in the Kearn-Sayre syndrome (KSS) and to establish criteria for the prevention of episodes of syncope or sudden cardiac death. METHODS AND RESULTS: This is a prospective monocentric study including KSS patients, with diagnosis based on clinical manifestations, muscle biopsy, and genetic tests, before the age of 18. All patients underwent cardiac screening examination with 12-lead electrocardiogram (ECG), 24-h Holter monitoring, and pacemaker (PM) interrogation twice a year. Fifteen patients (nine males, mean age 16.6 ± 3.9 years) with a sporadic KSS were recruited. All subjects manifested at least one of the intraventricular conduction defects (IVDs): 1 right bundle branch block (RBBB), 2 left anterior fascicular block (LAFB), 11 a bi-fascicular block (RBBB + LAFB), and 1 left posterior fascicular block. Most children with bi-fascicular block developed LAFB before the RBBB (P = 0.0049). In six patients, IVD degenerated into atrioventricular block (AVB). Endocavitary PM was implanted in 11 patients (6 with AVB and 5 with a bi-fascicular block), while an implantable cardioverter-defibrillator only in one patient with a non-sustained ventricular tachycardia. Four died at mean age of 14.7 ± 2.6 years, but none of them suddenly. CONCLUSION: Even a 'simple' ECG can predict the arrhythmic risk and the occurrence of catastrophic events in young patients with KSS. Left anterior fascicular block precedes RBBB in determining the bi-fascicular block and this can predict an inexorable progression of the conduction defects even in a short time. Pacemaker implantation may be indicated in these patients since the first bi-fascicular block manifestation.

Use of a Pediatric Syncope Unit Improves Diagnosis and Lowers Costs: A Hospital-Based Experience.

OBJECTIVES: To assess the effect of a dedicated pediatric syncope unit on the diagnostic and therapeutic management of children with suspected syncope. We also evaluated the effectiveness of the pediatric syncope unit model in decreasing unnecessary tests and hospitalizations, minimizing social costs, and improving diagnostic yield. STUDY DESIGN: This single-center cohort observational, prospective study enrolled 2278 consecutive children referred to Bambino Gesù Children's Hospital from 2012 to 2017. Characteristics of the study population, number and type of admission examinations, and diagnostic findings before the pediatric syncope unit was implemented (2012-2013) and after the pediatric syncope unit was implemented (2014-2015 and 2016-2017) were compared. RESULTS: The proportion of undefined syncope, number of unnecessary diagnostic tests performed, and number of hospital stay days decreased significantly (P < .0001), with an overall decrease in costs. A multivariable logistic regression analysis, adjusted for confounding variables (age, sex, number of diagnostic tests), the period after pediatric syncope unit (2016-2017) resulted as the best independent predictor of effectiveness for a defined diagnosis of syncope (P < .0001). CONCLUSIONS: Pediatric syncope unit organization with fast-tracking access more appropriate diagnostic tests is effective in terms of accuracy of diagnostic yield and reduction of costs.

Radiofrequency catheter ablation of left-sided accessory pathways in children using a new fluoroscopy integrated 3D-mapping system.

Introduction: Advances in 3D electroanatomic-mapping technologies have resulted in a safe and effective profile of radiofrequency (RF) catheter ablation. The aim of this study was to evaluate a different catheter ablation approach in patients with left-sided accessory pathways (APs). Methods and results: From January 2015 to December 2015, 30 patients (median age 11 years, median weight 45 kg) with manifest or concealed left-sided APs underwent RF catheter ablation with a new protocol. All procedures were performed with the CARTO UNIVU™ system, integrating electroanatomic maps with fluoroscopic views. A 7 Fr ablation catheter was inserted into the right femoral vein and advanced into the right atrium. Geometrical reconstruction and activation map of the right atrium, tricuspid annulus, and coronary sinus were acquired. The ablation catheter was then inserted into the left femoral artery and advanced through the aorta and aortic valve, creating an activation map of the mitral annulus. Catheter ablation was targeted to the site of the earliest activation. No complications occurred. The median procedure and fluoroscopy times were 130 min and 6 s, with a median fluoroscopy dose 0.5 mGy. An average of two catheters was used. Long-term success rate was 97% (29/30) at a median follow-up of 9.6 months. This approach reduced fluoroscopy time, dose and number of catheters used compared with manifest or concealed left-sided AP ablation using CARTO 3™ (P < 0.05). Conclusions: This new ablation protocol seems to be promising in reducing fluoroscopy exposure and number of catheters used during left-sided AP ablation in children.

Miniaturized Implantable Loop Recorder in Small Patients: An Effective Approach to the Evaluation of Subjects at Risk of Sudden Death.

BACKGROUND: The etiological diagnosis of syncope and/or palpitations in children is often challenging. However, when noninvasive conventional examinations are inconclusive, the subcutaneous miniaturized implantable loop recorder (ILR) is recommended. The aim of our study was to evaluate the efficacy of miniaturized cardiac implantable devices in the early diagnosis of arrhythmias in children ≤6 years. METHODS: From March 2014 to May 2015, 21 patients (median age 5 years) underwent implantation of miniaturized ILR at our Institution after a complete cardiac work up. Median follow-up was 10 months. RESULTS: One patient underwent device removal for pocket infection and one needed a pocket revision. Eleven (52%) patients did not show any symptom and/or arrhythmia. Eight patients experienced symptoms during ILR monitoring: six had no electrocardiographic abnormalities, two had significant sinus pauses. Two patients had significant arrhythmias without symptoms and in one of these a pacemaker was implanted. The overall diagnostic yield was 47%. CONCLUSIONS: Miniaturized ILR could be very useful to make a diagnosis and to decide future management strategies in small patients with undefined symptoms or severe cardiac diseases. Considering its characteristics, miniaturized ILR could start a new era in the diagnosis and follow-up of young patients with symptomatic and/or malignant arrhythmias.

Sinus bradycardia, junctional rhythm, and low-rate atrial fibrillation in Short QT syndrome during 20 years of follow-up: three faces of the same genetic problem.

We describe the case of an asymptomatic girl with sinus bradycardia and short QT interval at birth, junctional bradycardia in infancy requiring single-chamber pacemaker, atrial fibrillation in adolescence, and V141M mutation in the KCNQ1 gene. Atrial fibrillation recurred and became unresponsive to electrical or anti-arrhythmic therapy. During 20 years of follow-up, a progressive evolution from sinus node dysfunction to low-rate atrial fibrillation was observed.

Comparison of cryoablation with 3D mapping versus conventional mapping for the treatment of atrioventricular re-entrant tachycardia and right-sided paraseptal accessory pathways.

UNLABELLED: Aim Transcatheter cryoablation is a well-established technique for the treatment of atrioventricular nodal re-entry tachycardia and atrioventricular re-entry tachycardia in children. Fluoroscopy or three-dimensional mapping systems can be used to perform the ablation procedure. The aim of this study was to compare the success rate of cryoablation procedures for the treatment of right septal accessory pathways and atrioventricular nodal re-entry circuits in children using conventional or three-dimensional mapping and to evaluate whether three-dimensional mapping was associated with reduced patient radiation dose compared with traditional mapping. METHODS: In 2013, 81 children underwent transcatheter cryoablation at our institution, using conventional mapping in 41 children - 32 atrioventricular nodal re-entry tachycardia and nine atrioventricular re-entry tachycardia - and three-dimensional mapping in 40 children - 24 atrioventricular nodal re-entry tachycardia and 16 atrioventricular re-entry tachycardia. RESULTS: Using conventional mapping, the overall success rate was 78.1 and 66.7% in patients with atrioventricular nodal re-entry tachycardia or atrioventricular re-entry tachycardia, respectively. Using three-dimensional mapping, the overall success rate was 91.6 and 75%, respectively (p=ns). The use of three-dimensional mapping was associated with a reduction in cumulative air kerma and cumulative air kerma-area product of 76.4 and 67.3%, respectively (p<0.05). CONCLUSIONS: The use of three-dimensional mapping compared with the conventional fluoroscopy-guided method for cryoablation of right septal accessory pathways and atrioventricular nodal re-entry circuits in children was associated with a significant reduction in patient radiation dose without an increase in success rate.

Results of remote follow-up and monitoring in young patients with cardiac implantable electronic devices.

BACKGROUND: Remote monitoring is increasingly used in the follow-up of patients with cardiac implantable electronic devices. Data on paediatric populations are still lacking. The aim of our study was to follow-up young patients both in-hospital and remotely to enhance device surveillance. METHODS: This is an observational registry collecting data on consecutive patients followed-up with the CareLink system. Inclusion criteria were a Medtronic device implanted and patient's willingness to receive CareLink. Patients were stratified according to age and presence of congenital/structural heart defects (CHD). RESULTS: A total of 221 patients with a device - 200 pacemakers, 19 implantable cardioverter defibrillators, and two loop recorders--were enrolled (median age of 17 years, range 1-40); 58% of patients were younger than 18 years of age and 73% had CHD. During a follow-up of 12 months (range 4-18), 1361 transmissions (8.9% unscheduled) were reviewed by technicians. Time for review was 6 ± 2 minutes (mean ± standard deviation). Missed transmissions were 10.1%. Events were documented in 45% of transmissions, with 2.7% yellow alerts and 0.6% red alerts sent by wireless devices. No significant differences were found in transmission results according to age or presence of CHD. Physicians reviewed 6.3% of transmissions, 29 patients were contacted by phone, and 12 patients underwent unscheduled in-hospital visits. The event recognition with remote monitoring occurred 76 days (range 16-150) earlier than the next scheduled in-office follow-up. CONCLUSIONS: Remote follow-up/monitoring with the CareLink system is useful to enhance device surveillance in young patients. The majority of events were not clinically relevant, and the remaining led to timely management of problems.

Ventricular pre-excitation: symptomatic and asymptomatic children have the same potential risk of sudden cardiac death.

AIMS: Children and adolescents with ventricular pre-excitation (VPE) are at increased risk for sudden cardiac death (SCD). Although antiarrhythmic therapy and catheter ablation are well established temporary or definitive treatments for patients with Wolff-Parkinson-White (WPW) syndrome, the optimal management of children with asymptomatic VPE remains to be clearly defined. On the basis of the most recent guidelines and recommendations, the aim of this study was to determine the electrophysiological characteristics of young patients with VPE and WPW syndrome to assess and compare their potential risk of SCD. METHODS AND RESULTS: We retrospectively investigated 124 consecutive young patients with VPE (51 with WPW syndrome and 73 asymptomatic) who underwent transoesophageal electrophysiological study. At baseline, atrioventricular reentrant tachycardia (AVRT) was induced in 13 WPW vs. 10 asymptomatic patients (25.5 vs. 13.7%, P = NS). Atrial fibrillation (AF) was induced in 13 WPW vs. 15 asymptomatic patients (25.5 vs. 20.5%, P = NS). A shortest pre-excited R-R interval (SPERRI) ≤250 ms during AF was found in four WPW vs. six asymptomatic patients (30.8 vs. 40%, P = NS). During isoproterenol infusion or stress testing, AVRT was induced in 31 of 44 WPW vs. 33 of 69 asymptomatic patients (70.4 vs. 47.8%, P = 0.018). Atrial fibrillation was induced in 12 of 44 WPW vs. 21 of 69 asymptomatic patients (27.3 vs. 30.4%, P = NS). A SPERRI ≤ 210 ms was found in 6 of 12 WPW vs. 10 of 21 asymptomatic patients (50 vs. 47.6%, P = NS). No statistically significant correlation was observed between accessory pathway location and symptoms, AVRT/AF inducibility, or mean APERP/SPERRI values. CONCLUSION: Children and adolescents with WPW syndrome have a higher rate of AVRT inducibility than asymptomatic patients. However, no differences between the two groups were found in atrial vulnerability and parameters related to the risk of SCD.

Evaluation of microRNA-10b prognostic significance in a prospective cohort of breast cancer patients.

BACKGROUND: MicroRNA-10b (miR-10b) has a prominent role in regulating tumor invasion and metastasis by targeting the HOXD10 transcriptional repressor and has been found up-regulated in several tumor types. METHODS: We evaluated the expression of miR-10b in paired tumor and normal specimens obtained from a prospective cohort of breast cancer patients with at least 36 months follow-up enrolled according to the REMARK guidelines (n = 150). RNA quality was measured and only samples with RNA Integrity Number (RIN) ≥7.0 were analyzed. RESULTS: The relative expression of miR-10b in tumor as compared to its normal counterpart (RER) was determined by RT-qPCR. miR-10b RERs were higher in the subgroup of patients with synchronous metastases (n = 11, Median 0.25; IQR 0.11-1.02) as compared with patients without metastases (n = 90, Median 0.09; IQR 0.04-0.29) (p = 0.028). In the subgroup of patients without synchronous metastases (n = 90), higher miR-10b RERs were associated with increased risk of disease progression and death in both univariable (HR 1.16, p = 0.021 and HR 1.20, p = 0.015 respectively for 0.10 unitary increase of miR-10b RERs levels) and multivariable (HR1.30, p < 0.001, and HR 1.31, p = 0.003 respectively for 0.10 unitary increase of miR-10b RERs levels) Cox regression models. The addition of miR-10b RERs to the Nottingham Prognostic Index (NPI) provided an improvement in discrimination power and risk reclassification abilities for the clinical outcomes at 36 months. Survival C-indices significantly increased from 0.849 to 0.889 (p = 0.009) for OS and from 0.735 to 0.767 (p = 0.050) for DFS. CONCLUSIONS: Our results provide evidences that the addition of miR-10b RERs to the prognostic factors used in clinical routine could improve the prediction abilities for both overall mortality and disease progression in breast cancer patients.

Cryoablation of AVNRT in children and adolescents: early intervention leads to a better outcome.

INTRODUCTION: Currently, transcatheter cryoablation is a well-established technique for the treatment of atrioventricular nodal reentry tachycardia (AVNRT) in children. In the past decade, many studies have focused on identifying factors that may affect acute and long-term outcome, but none has been shown to be strongly predictive of treatment success. The aim of our study was to determine whether patient age and cryoablation method correlate with acute and long-term success. METHODS AND RESULTS: We retrospectively reviewed 202 consecutive patients (98 male, mean age 11.5 years; range: 4-20 years) who underwent cryoablation for AVNRT at our institution from October 2002 to August 2012. Patients were divided into 2 groups according to age: group A <12 years (n = 101) and group B ≥12 years (n = 101). A single lesion or linear lesion technique was employed. A total of 217 cryoablation procedures were performed: 106 (49%) in group A and 111 (51%) in group B. All patients were evaluated in our postoperative follow-up program. The overall recurrence rate was 10.9% (22/202). AVNRT recurrence was significantly lower in group A than in group B (4.95% vs 16.8%, P = 0.000). No significant differences in recurrence rate were observed between groups when using the single lesion versus linear lesion technique. There were no permanent cryoablation-related complications. CONCLUSION: Our findings show that cryoablation had no complications and a very good success rate. Type of cryolesion is not predictive of long-term success, whereas lower recurrence rate is achieved when cryoablation is performed at a younger age.

The role of macrophages polarization in predicting prognosis of radically resected gastric cancer patients.

Tumour-associated Macrophages (TAM) present two different polarizations: classical (M1) characterized by immunostimulation activity and tumour suppression; alternative (M2) characterized by tumour promotion and immune suppression. In this retrospective study, we evaluated the correlation between the two forms of TAM with survival time in radically resected gastric cancer patients. A total of 52 chemo- and radio-naive patients were included. Two slides were prepared for each patient and double-stained for CD68/NOS2 (M1) or CD68/CD163 (M2) and five representative high-power fields per slide were evaluated for TAM count. The median value of the two macrophage populations density and the median value of M1/M2 ratio were used as cut-off. Twenty-seven patients with M1 density above-the-median had a significantly higher survival compared to those below the median. Twenty-six patients with M1/M2 ratio above the median showed median OS of 27.2 months compared to 15.5 months of the patients below the median. No association between M2 macrophage density and patient's outcome was found. In multivariate analysis, M1/M2 was a positive independent predictor of survival. The M1 macrophage density and M1/M2 ratio, as confirmed in multivariate analysis, are factors that can help in predicting patients survival time after radical surgery for gastric cancer.

Cryoablation of right-sided accessory pathways in children: report of efficacy and safety after 10-year experience and follow-up.

AIMS: The aim of this study was to report the 10-year experience of our Institution in cryoablation of supraventricular tachycardia due to a right accessory pathway (AP). METHODS AND RESULTS: Seventy-one cryoablations of right AP were performed between July 2002 and October 2011 in our Institution in 66 patients (mean age 12 + 3 years, 56% males). Acute procedural success rate was 97%: 80% in patients with concealed AP and 100% in those with manifest AP (P < 0.05). Acute procedural success rate was not related to institutional experience. No permanent complication occurred. Sixteen patients had recurrences during the follow-up (18.6 ± 6.6 months; range 3-111), 13 within the first month of follow-up, 2 within the 6 months of follow-up, and 1 within 12 months of follow-up. Cox regression showed that sex, patient age, number of delivered cryo-bonus, and presence of manifest or concealed AP are not independent predictors of procedural success. Among the 16 patients with recurrences, in 10 a cryoablation redo was successful and with no further AP recurrences. The mean fluoroscopy time was 28.4 min (range 19.7-44.6) with a significant decrease (P = 0.033) in relation to the increase of the institutional experience. There were no permanent ablation-related complications. CONCLUSION: Cryoablation of right-sided AP is effective and very safe in children. Better results are achieved in manifest AP. The learning curve has a real impact in the attempt to reduce the fluoroscopy time.

Percutaneous axillary vein approach in pediatric pacing: comparison with subclavian vein approach.

AIMS: The subclavian vein approach has been used for 20 years in our center for pacemaker (PM) implantation in children, but it carries risks of hemothorax/pneumothorax and lead fracture, which could be reduced by axillary vein approach. METHODS AND RESULTS: This is a prospective study enrolling the first 48 consecutive pediatric patients (age: 12.3 ± 4.6 years) who underwent PM/implantable cardioverter-defibrillator leads implantation through axillary vein (guided by contrast venography) between 2009 and 2012 (group I). A comparison was made with the outcomes of the subclavian vein approach (group II) in 41 patients, age 12.3 ± 4.8 years, consecutively enrolled between 2006 and 2011. The two groups showed no significant differences for the variables examined except for follow-up, longer in group II, and for alternative ventricular pacing sites, more frequent in group I. Axillary vein diameter was 7.9 ± 1.7 mm and showed positive correlation with height (r = 0.77). The axillary vein approach was effective in 93.7% of patients. The unsuccessful procedures occurred in patients with significantly lower age and smaller venous diameters. The subclavian vein approach was effective in 100% of patients. Sixty-two leads were implanted in group I, 54 in group II. There were neither intraoperative complications in both the groups, nor significant differences for early and late complications. CONCLUSIONS: The axillary vein approach for PM implantation in children is effective and safe for physicians skilled with subclavian vein approach. Younger patients with smaller vein diameters are at low risk for unsuccessful procedure.

Efficacy of temporary positive expiratory pressure (TPEP) in patients with lung diseases and chronic mucus hypersecretion. The UNIKO® project: a multicentre randomized controlled trial.

OBJECTIVE: To evaluate whether temporary positive expiratory pressure provides benefit in patients with lung diseases and chronic hypersecretion. DESIGN: Single blind multicentre randomized trial. SETTING: Five Italian rehabilitation centres. PARTICIPANTS: Ninety-eight patients with chronic obstructive pulmonary disease and/or chronic bronchitis (n=78), or bronchiectasis (n=20), with a peak cough expiratory flow >150 l/min and sputum production >30 ml/day, randomly included into two treatment groups. INTERVENTIONS: For 10 consecutive days, the active group performed twice a day 20-minute cycles of manually assisted breathing techniques in sequence with the addition of 15 minutes of temporary positive expiratory pressure, while the control group was treated by manually assisted breathing techniques alone. MEASURES: Within and between group changes of arterial oxygenation index, lung volumes and respiratory muscles strength were recorded at enrolment and after 3 and 10 treatment sessions. Pre-to-post treatment change of sputum volume and bronchial encumbrance (Δ-visual analog scale), sputum density and purulence were compared daily within the study period. RESULTS: No significant changes were recorded for the oxygenation index, while dynamic lung volumes and respiratory muscle strength significantly (P <0.05) improved in the active group. The group comparison analysis of the pre-to-post change showed that inspiratory capacity was significantly higher in the active than in the control group (+19.5% and +2.2%, P=0.044) at day 10. A greater improvement in Δ-visual analog scale was recorded in the active group at day 3 and 8. CONCLUSIONS: These preliminary data suggest that temporary positive expiratory pressure improves lung volumes and speeds up the improvement of bronchial encumbrance in patients with lung diseases and hypersecretion.

Feasibility of Comprehensive Genomic Profiling (CGP) in Real-Life Clinical Practice.

In advanced or metastatic settings, Comprehensive Genomic Profiling (CGP) allows the evaluation of thousands of gene alterations with the goal of offering new opportunities for personalized treatment in solid tumors. This study evaluated the CGP Success Rate in a real-life cohort of 184 patients enrolled in a prospective clinical trial. CGP data were compared with the routine molecular testing strategy adopted in-house. Sample age, tumor area, and the percentage of tumor nuclei were recorded for CGP analysis. We found that 150/184 (81.5%) samples resulted in satisfying CGP reports. The CGP Success Rate was higher in samples from surgical specimens (96.7%) and in specimens that had been stored (sample age) for less than six months (89.4%). Among the inconclusive CGP reports, 7/34 (20.6%) were optimal samples, according to CGP sample requirements. Moreover, with the in-house molecular testing approach, we could obtain clinically relevant molecular data in 25/34 (73.5%) samples that had inconclusive CGP reports. In conclusion, despite the fact that CGP offers specific therapeutical options in selected patients, our data suggest that the standard molecular testing strategy should not be replaced in routine molecular profiling.

Next generation diagnostic algorithm in non-small cell lung cancer predictive molecular pathology: The KWAY Italian multicenter cost evaluation study.

AIMS: The KWAY project aims to investigate the economic sustainability of the up-front NGS technologies adoption in the analysis of clinically relevant molecular alterations in NSCLC patients. METHODS: The diagnostic workflow and the related sustained costs of five Italian referral centers were assessed in four different evolving scenarios were analyzed. For each scenario, two alternative testing strategies were evaluated: the Maximized Standard strategy and the Maximized NGS strategy. RESULTS: For each center, the robustness of obtained results was verified through a deterministic sensitivity analysis, observing the variation of total costs based on a variation of ±20 % of the input parameters and ensuring that results would present a consistent behavior compared to the original ones. CONCLUSIONS: our project, highlighted that the adoption of NGS allows to save personnel time dedicated to testing activities and to reduce the overall cost of testing per patient.