Impact of 4D-Flow CMR Parameters on Functional Evaluation of Fontan Circulation.

We sought to evaluate the potential clinical role of 4D-flow cardiac magnetic resonance (CMR)-derived energetics and flow parameters in a cohort of patients' post-Fontan palliation. In patients with Fontan circulation who underwent 4D-Flow CMR, streamlines distribution was evaluated, as well a 4D-flow CMR-derived energetics parameters as kinetic energy (KE) and energy loss (EL) normalized by volume. EL/KE index as a marker of flow efficiency was also calculated. Cardiopulmonary exercise test (CPET) was also performed in a subgroup of patients. The population study included 55 patients (mean age 22 ± 11 years). The analysis of the streamlines revealed a preferential distribution of the right superior vena cava flow for the right pulmonary artery (62.5 ± 35.4%) and a mild preferential flow for the left pulmonary artery (52.3 ± 40.6%) of the inferior vena cave-pulmonary arteries (IVC-PA) conduit. Patients with heart failure (HF) presented lower IVC/PA-conduit flow (0.75 ± 0.5 vs 1.3 ± 0.5 l/min/m2, p = 0.004) and a higher mean flow-jet angle of the IVC-PA conduit (39.2 ± 22.8 vs 15.2 ± 8.9, p < 0.001) than the remaining patients. EL/KE index correlates inversely with VO2/kg/min: R: - 0.45, p = 0.01 peak, minute ventilation (VE) R: - 0.466, p < 0.01, maximal voluntary ventilation: R:0.44, p = 0.001 and positively with the physiological dead space to the tidal volume ratio (VD/VT) peak: R: 0.58, p < 0.01. From our data, lower blood flow in IVC/PA conduit and eccentric flow was associated with HF whereas higher EL/KE index was associated with reduced functional capacity and impaired lung function. Larger studies are needed to confirm our results and to further improve the prognostic role of the 4D-Flow CMR in this challenging population.

Top-Down Proteomics of Human Saliva, Analyzed with Logistic Regression and Machine Learning Methods, Reveal Molecular Signatures of Ovarian Cancer.

Ovarian cancer (OC) is the most lethal of all gynecological cancers. Due to vague symptoms, OC is mostly detected at advanced stages, with a 5-year survival rate (SR) of only 30%; diagnosis at stage I increases the 5-year SR to 90%, suggesting that early diagnosis is essential to cure OC. Currently, the clinical need for an early, reliable diagnostic test for OC screening remains unmet; indeed, screening is not even recommended for healthy women with no familial history of OC for fear of post-screening adverse events. Salivary diagnostics is considered a major resource for diagnostics of the future. In this work, we searched for OC biomarkers (BMs) by comparing saliva samples of patients with various stages of OC, breast cancer (BC) patients, and healthy subjects using an unbiased, high-throughput proteomics approach. We analyzed the results using both logistic regression (LR) and machine learning (ML) for pattern analysis and variable selection to highlight molecular signatures for OC and BC diagnosis and possibly re-classification. Here, we show that saliva is an informative test fluid for an unbiased proteomic search of candidate BMs for identifying OC patients. Although we were not able to fully exploit the potential of ML methods due to the small sample size of our study, LR and ML provided patterns of candidate BMs that are now available for further validation analysis in the relevant population and for biochemical identification.

The Clinical Profile of Tremor in Parkinson's Disease.

Background: Tremor is one of the most troublesome manifestations of Parkinson's Disease (PD) and its response to dopaminergic medication is variable; an evidence-based framework of PD tremor is lacking yet needed to inform future investigations. Objective: To perform a comprehensive longitudinal analysis on the clinical characteristics, course and response to dopaminergic medication of tremor in de-novo PD. Methods: Three hundred ninety-seven participants were recruited in the Parkinson Progressive Markers Initiative, a prospective observational cohort study in early de-novo PD. Rest, postural and kinetic tremor scores were extracted from the Movement Disorders Society-Unified Parkinson's Disease Rating Scale. Progression from baseline to 7-year follow-up of rest, postural and kinetic tremor scores, and their response to in-clinic dopaminergic medication were analyzed through linear mixed-effects models adjusted for age, sex and disease duration at enrollment. A sensitivity analysis was conducted through subgroup and imputation analyses. Results: 382 (96.2%) participants showed tremor and 346 (87.2%) showed rest tremor in at least one assessment over 7 years. Off-state rest, postural and kinetic tremor scores increased significantly over time, coupled with a significant effect of dopaminergic medication in reducing tremor scores. However, at each assessment, tremor was unresponsive to in-clinic dopaminergic medication in at least 20% of participants for rest, 30% for postural and 38% for kinetic tremor. Conclusions: PD tremor is a troublesome manifestation, with increasing severity and variable response to medications. This analysis details the current clinical natural history of tremor in early-to-mid stage PD, outlining an evidence-based framework for future pathophysiological and interventional studies.

Overcoming Underpowering in the Outcome Analysis of Repaired-Tetralogy of Fallot: A Multicenter Database from the CMR/CT Working Group of the Italian Pediatric Cardiology Society (SICPed).

Background: Managing repaired tetralogy of Fallot (TOF) patients is still challenging despite the fact that published studies identified prognostic clinical or imaging data with rather good negative predictive accuracy but weak positive predictive accuracy. Heterogeneity of the initial anatomy, the surgical approach, and the complexity of the mechanism leading to dilation and ventricular dysfunction explain the challenge of predicting the adverse event in this population. Therefore, risk stratification and management of this population remain poorly standardized. Design: The CMR/CT WG of the Italian Pediatric Cardiology Society set up a multicenter observational clinical database of repaired TOF evaluations. This registry will enroll patients retrospectively and prospectively assessed by CMR for clinical indication in many congenital heart diseases (CHD) Italian centers. Data collection in a dedicated platform will include surgical history, clinical data, imaging data, and adverse cardiac events at 6 years of follow-up. Summary: The multicenter repaired TOF clinical database will collect data on patients evaluated by CMR in many CHD centers in Italy. The registry has been set up to allow future research studies in this population to improve clinical/surgical management and risk stratification of this population.

Prognostic Role of Lung Ultrasound in Children with Bronchiolitis: Multicentric Prospective Study.

There is increasing recognition of the role of lung ultrasound (LUS) to assess bronchiolitis severity in children. However, available studies are limited to small, single-center cohorts. We aimed to assess a qualitative and quantitative LUS protocol to evaluate the course of bronchiolitis at diagnosis and during follow-up. This is a prospective, multicenter study. Children with bronchiolitis were stratified according to clinical severity and underwent four LUS evaluations at set intervals. LUS was classified according to four models: (1) positive/negative; (2) main LUS pattern (normal/interstitial/consolidative/mixed) (3) LUS score; (4) LUS score with cutoff. Two hundred and thirty-three children were enrolled. The baseline LUS was significantly associated with bronchiolitis severity, using both the qualitative (positive/negative LUS p < 0.001; consolidated/normal LUS pattern or mixed/normal LUS p < 0.001) and quantitative models (cutoff score > 9 p < 0.001; LUS mean score p < 0.001). During follow-up, all LUS results according to all LUS models improved (p < 0.001). Better cut off value was declared at a value of >9 points. Conclusions: Our study supports the role of a comprehensive qualitative and quantitative LUS protocol for the identification of severe cases of bronchiolitis and provides data on the evolution of lung aeration during follow-up.

Hands-feet wireless devices: Test-retest reliability and discriminant validity of motor measures in Parkinson's disease telemonitoring.

BACKGROUND: Telemonitoring, a branch of telemedicine, involves the use of technological tools to remotely detect clinical data and evaluate patients. Telemonitoring of patients with Parkinson's disease (PD) should be performed using reliable and discriminant motor measures. Furthermore, the method of data collection and transmission, and the type of subjects suitable for telemonitoring must be well defined. OBJECTIVE: To analyze differences in patients with PD and healthy controls (HC) with the wearable inertial device SensHands-SensFeet (SH-SF), adopting a standardized acquisition mode, to verify if motor measures provided by SH-SF have a high discriminating capacity and high intraclass correlation coefficient (ICC). METHODS: Altogether, 64 patients with mild-to-moderate PD and 50 HC performed 14 standardized motor activities for assessing bradykinesia, postural and resting tremors, and gait parameters. SH-SF inertial devices were used to acquire movements and calculate objective motor measures of movement (total: 75). For each motor task, five or more biomechanical parameters were measured twice. The results were compared between patients with PD and HC. RESULTS: Fifty-eight objective motor measures significantly differed between patients with PD and HC; among these, 32 demonstrated relevant discrimination power (Cohen's d > 0.8). The test-retest reliability was excellent in patients with PD (median ICC = 0.85 right limbs, 0.91 left limbs) and HC (median ICC = 0.78 right limbs, 0.82 left limbs). CONCLUSION: In a supervised environment, the SH-SF device provides motor measures with good results in terms of reliability and discriminant ability. The reliability of SH-SF measurements should be evaluated in an unsupervised home setting in future studies.

Operative Use of Thoracic Ultrasound in Respiratory Medicine: A Clinical Study.

For over 15 years, thoracic ultrasound has been applied in the evaluation of numerous lung diseases, demonstrating a variable diagnostic predictive power compared to traditional imaging techniques such as chest radiography and CT. However, in unselected pulmonary patients, there are no rigorous scientific demonstrations of the complementarity of thoracic ultrasound with traditional and standardized imaging techniques that use radiation. In this study 101 unselected pulmonary patients were evaluated blindly with ultrasound chest examinations during their hospital stay. Other instrumental examinations, carried out during hospitalization, were standard chest radiography, computed tomography (CT), and, when needed, radioisotopic investigation and cardiac catheterization. The operator who performed the ultrasound examinations was unaware of the anamnestic and clinical data of the patients. Diffuse fibrosing disease was detected with a sensitivity, specificity and diagnostic accuracy of 100%, 95% and 97%, respectively. In pleural effusions, ultrasound showed a sensitivity, specificity and diagnostic accuracy of 100%. In consolidations, the sensitivity, specificity and diagnostic accuracy were 83%, 98% and 93%, respectively. Low values of sensitivity were recorded for surface nodulations of less than one centimeter. Isolated subpleural ground glass densities were identified as White Lung with a sensitivity of 72% and a specificity of 86%. Only the associations Diffuse ultrasound findings/Definitive fibrosing disease, Ultrasound Consolidation/Definitive consolidation and non-diffuse ultrasound artefactual features/Definitive vascular pathology (pulmonary hypertension, embolism) were statistically significant with adjusted residuals of 7.9, 7 and 4.1, respectively. The obtained results show how chest ultrasound is an effective complementary diagnostic tool for the pulmonologist. When performed, as a complement to the patient's physical examination, it can restrict the diagnostic hypothesis in the case of pleural effusion, consolidation and diffuse fibrosing disease of the lung.

Role of cardiac MRI in the prediction of pre-Fontan end-diastolic ventricular pressure.

BACKGROUND: Growing evidence has emphasised the importance of ventricular performance in functionally single-ventricle patients, particularly concerning diastolic function. Cardiac MRI has been proposed as non-invasive alternative to pre-Fontan cardiac catheterisation in selected patients. AIM OF THE STUDY: To identify clinical and cardiac magnetic resonance predictors of high pre-Fontan end-diastolic ventricular pressure. METHOD: In a retrospective single-centre study, 38 patients with functionally univentricular heart candidate for Fontan intervention, who underwent pre-Fontan cardiac catheterisation, beside a comprehensive cardiac MRI, echocardiographic, and clinical assessment were included. Medical and surgical history, cardiac magnetic resonance, cardiac catheterisation, echocardiographic, and clinical data were recorded. We investigated the association between non-invasive parameters and cardiac catheterisation pre-Fontan risk factors, in particular with end-diastolic ventricular pressure. Moreover, the impact of conventional invasive pre-Fontan risk factor on post-operative outcome as also assessed. RESULTS: Post-operative complications were associated with higher end-diastolic ventricular pressure and Mayo Clinic indexes (p < 0.01 and p = 0.05, respectively). At receiver operating characteristic curve analysis end-diastolic ventricular pressure ≥ 10.5 mmHg predicted post-operative complications with a sensitivity of 75% and specificity of 88% (AUC: 0.795, 95% CI 0.576;1.000, p < 0.05). At multivariate analysis, both systemic right ventricle (OR: 23.312, 95% CI: 2.704-200.979, p < 0.01) and superior caval vein indexed flow (OR: 0.996, 95% CI: 0.993-0.999, p < 0.05) influenced end-diastolic ventricular pressure ≥ 10.5 mmHg. CONCLUSIONS: A reduced superior caval vein flow, evaluated at cardiac magnetic resonance, is associated with higher end-diastolic ventricular pressure a predictor of early adverse outcome in post-Fontan patients.

Immunosuppressant-Responsive Enteropathy and Non-Responsive Enteropathy in Dogs: Prognostic Factors, Short- and Long-Term Follow Up.

A multicentre prospective study was performed to assess whether clinical, hematobiochemical, endoscopic and histopathological parameters were associated with mortality, clinical response and relapse of disease in short- and long-term follow-up of a total of 165 dogs with chronic inflammatory enteropathy, of which 150 had immunosuppressant responsive enteropathy (IRE), and 15 had non-responsive enteropathy (NRE) dogs. Clinical severity (CCECAI) was evaluated from presentation (T0) to 18 months (T18) from diagnosis. T0 body condition score (BCS), selected haematological parameters and endoscopic and histopathological scores were evaluated. Presence/absence of histopathological duodenal lesions was recorded. Responders were evaluated using CCECAI at T1. Relapse was evaluated from T3 to T18. Long-term responders included dogs who responded at T1 and showed no relapse. Dogs were divided into responders/non-responders, survivors/non-survivors and relapsed/non-relapsed. At T1, 15/165 dogs (9%) were considered NRE. Sixteen dogs (11%) were considered relapsed at T3, 8% at T6 and 10% at T12, and none of 96 dogs relapsed at T18. NREs showed significantly lower BCS than IREs. Non-survivors showed a significantly lower serum albumin concentration and BCS than survivors. Non-responders, relapsed or non-survivors had higher presence of lacteal dilatation compared to long-term responders. Dogs with IRE showed a good clinical course with a low relapse rate, with only a few dogs in the NRE group. Reduction of BCS, albumin and lacteal dilatation at diagnosis may be considered negative prognostic factors for response, mortality and long-term disease remission.

The impact of native Fallot anatomy on future therapeutic requirements and outcomes at follow-up.

BACKGROUND: In patients with repaired Fallot, subsequent surgical or interventional procedures and adverse cardiac events are frequent. We aimed to evaluate the impact of a simple pre-operative anatomic classification based on the size of the pulmonary valve (PV) annulus and branches on future therapeutic requirements and outcomes. METHOD: This is a single-center retrospective analysis of patients operated for Fallot before the age of 2 years, from January 1990. Pre-operative anatomy, surgical and interventional procedures and adverse events were extrapolated from clinical records. RESULTS: Among the 312 patients, a description of the PV and pulmonary arteries (PAs) native anatomy was known in 239 patients (male:147, 61.5%), which were divided in the following 3 groups: group 1 (65 patients) with normal size of both PV and PAs; group 2 (108 patients) with PV hypoplasia but normal size PAs; group 3 (66 patients) with concomitant hypoplasia of the PV and PAs. During the 12.7 years (IQR 6.7-17) follow-up time, 23% of patients required at least one surgical or interventional procedure. At Kaplan-Meier analysis, there was a significant difference in requirement of future surgical or interventional procedures among the 3 groups (p < 0,001). At multivariate Cox regression analysis, hypoplasia of PV and PAs was an independent predictor of subsequent procedures (HR:3.1,CI:1.06-9.1, p = 0.03). CONCLUSION: Native anatomy in Tetralogy of Fallot patients affects surgical strategy and follow-up. It would be therefore advisable to tailor patient's counseling and follow-up according to native anatomy, rather than following a standardized protocol.

Testing olfactory dysfunction in acute and recovered COVID-19 patients: a single center study in Italy.

BACKGROUND: Olfactory dysfunction in coronavirus disease 2019 (COVID-19) is common during acute illness and appears to last longer than other symptoms. The aim of this study was to objectively investigate olfactory dysfunction in two cohorts of patients at two different stages: during acute illness and after a median recovery of 4 months. METHODS: Twenty-five acutely ill patients and 26 recovered subjects were investigated. Acute patients had a molecular diagnosis of COVID-19; recovered subjects had a positive antibody assay and a negative molecular test. A 33-item psychophysical olfactory identification test tailored for the Italian population was performed. RESULTS: Median time from symptoms onset to olfactory test was 33 days in acute patients and 122 days in recovered subjects. The former scored a significantly higher number of errors at psychophysical testing (median [IQR]: 8 [13] vs 3 [2], p < 0.001) and were more frequently hyposmic (64% vs 19%, p = 0.002). Recovered subjects reported a variable time to subjective olfactory recovery, from days up to 4 months. Participants included in the study reported no significant nasal symptoms at olfactory testing. Among recovered subject who reported olfactory loss during acute COVID-19, four (27%) were still hyposmic. Demographic and clinical characteristics did not show significant associations with olfactory dysfunction. CONCLUSION: Moderate-to-severe hospitalized patients showed a high level and frequency of olfactory dysfunction compared to recovered subjects. In the latter group, subjects who reported persisting olfactory dysfunction showed abnormal scores on psychophysical testing, indicating that, at least in some subjects, persistent hyposmia may represent a long-term sequela of COVID-19.

Predictive factors of mortality in open abdomen for abdominal sepsis: a retrospective cohort study on 113 patients.

Over the past few years, the open abdomen (OA) as a part of Damage Control Surgery (DCS) has been introduced as a surgical strategy with the intent to reduce the mortality of patients with severe abdominal sepsis. Aims of our study were to analyze the OA effects on patients with abdominal sepsis and identify predictive factors of mortality. Patients admitted to our institution with abdominal sepsis requiring OA from 2010 to 2019 were retrospectively analyzed. Primary outcomes were mortality, morbidity and definitive fascial closure (DFC). Comparison between groups was made via univariate and multivariate analyses. On 1474 patients operated for abdominal sepsis, 113 (7.6%) underwent OA. Male gender accounted for 52.2% of cases. Mean age was 68.1 ± 14.3 years. ASA score was > 2 in 87.9%. Mean BMI, APACHE II score and Mannheim Peritonitis Index were 26.4 ± 4.9, 15.3 ± 6.3, and 22.6 ± 7.3, respectively. A negative pressure wound system technique was used in 47% of the cases. Overall, mortality was 43.4%, morbidity 76.6%, and DFC rate was 97.8%. Entero-atmospheric fistula rate was 2.2%. At multivariate analysis, APACHE II score (OR 1.18; 95% CI 1.05-1.32; p = 0.005), Frailty Clinical Scale (OR 4.66; 95% CI 3.19-6.12; p < 0.0001) and ASA grade IV (OR 7.86; 95% CI 2.18-28.27; p = 0.002) were significantly associated with mortality. OA seems to be a safe and reliable treatment for critically ill patients with severe abdominal sepsis. Nonetheless, in these patients, co-morbidity and organ failure remain the major obstacles to a better prognosis.

Cardiac troponins: are there any differences between T and I?

The most recent international guidelines recommend the measurement of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) using high-sensitivity methods (hs-cTn) for the detection of myocardial injury and the differential diagnosis of acute coronary syndromes. Myocardial injury is a prerequisite for the diagnosis of acute myocardial infarction, but also a distinct entity. The 2018 Fourth Universal Definition of Myocardial Infarction states that myocardial injury is detected when at least one value above the 99th percentile upper reference limit is measured in a patient with high-sensitivity methods for cTnI or cTnT. Not infrequently, increased hs-cTnT levels are reported in patients with congenital or chronic neuromuscular diseases, while the hs-cTnI values are often in the normal range. Furthermore, some discrepancies between the results of laboratory tests for the two troponins are occasionally found in individuals apparently free of cardiac diseases, and also in patients with cardiac diseases. In this review article, authors discuss the biochemical, pathophysiological and analytical mechanisms which may cause discrepancies between hs-cTnI and hs-cTnT test results.

Incidence and type of brain herniation associated with intracranial meningioma in dogs and cats.

The incidence of brain herniation (BH) in association with intracranial meningioma (ICM) in dogs and cats is poorly described. The aim of this study was to evaluate the rate and type of brain herniations in client-owned dogs and cats with ICMs and to determine the meningioma volume (MV) relative to cranial cavity volume (CCV). A retrospective magnetic resonance imaging (MRI) analysis study of 24 cats and 45 dogs with ICMs was conducted to ascertain the presence and characteristics of BH. MV and CCV were measured and their ratio was calculated for each animal. Correlations of MV/CCV with independent variables were analyzed. BH was encountered in 24/24 cats (100%) and 30/45 dogs (66.7%) with ICMs. In cats, the most frequent presentation was foramenal herniation (FMH; 23/24, 95.8%), followed by caudotentorial (CTH; 21/24, 87.5%) and subfalcine (SH; 18/24, 75.0%) herniation. In dogs, the most frequent presentation was SH (28/45; 62.2%), followed by CTH (9/45; 20%) and FMH (2/45; 4.4%). Relative to dogs, cats with ICM had greater incidences of FMH (P<0.001) and CTH (P<0.001). Mean MV/CCV ratio was higher in cats (0.098) than in dogs (0.038; P<0.001). The most common clinical sign of ICM was altered behavior in cats (43%, P<0.01) and seizures in dogs (74.4%, P<0.001). In conclusion, cats were found to be more likely than dogs to present FMH and CTH, with a proportionally greater neoplasia volume.

Impact of right atrium dimension on adverse outcome after pulmonary valve replacement in repaired Tetralogy of Fallot patients.

The hemodynamic impact of residual pulmonary regurgitation (PR) in repaired Tetralogy of Fallot (rTOF) has been well demonstrated. However, markers driving the decision making process to indicate the ideal timing of pulmonary valve replacement (PVR) are still uncertain. Furthermore, very few studies have included the right atrium (RA) dilatation as a preoperative risk factor for post-PVR clinical adverse outcome. The aim of this study was to investigate the impact of pre-PVR right atrial dilation on adverse outcomes in rTOF. We retrospectively reviewed from our CMR database all rTOF patients who underwent CMR study before and after PVR. Detailed clinical and surgical history were collected, in addition to imaging data. The composite primary and secondary post-PVR end points were also recorded. The study cohort consisted of 41 patients (mean age at PVR repair 27.4 ± 10 years). As expected, end-diastolic and end-systolic right ventricle (RV) volumes significantly decreased after PVR (p < 0.001). The RV reverse remodeling, defined by ΔRVEDVi and ΔRVESVi, was associated with both pre-PVR RVEDVi and RVESVi. The higher the pre-PVR RV volumes, more the RV reverse remodeling will be obtained post-surgery. Patients who experienced an adverse outcome were older at pre-PVR, they had a higher Nt-ProBNP, worse VO2/kg/min, more significant tricuspid regurgitation and more dilated RA. The association with the RA dilatation persists and becomes even more significant if we exclude patients who had tricuspid repair beside RVOT surgical reconstruction. Besides RV volumes and function, RA dimensions may play a pivotal role in the decision making of TOF patients.

Prognostic Value of Lung Ultrasound B-Lines in Systemic Sclerosis.

BACKGROUND: A high percentage of systemic sclerosis (SSc) patients experience interstitial lung disease (ILD) during the disease course. Recent data have shown that lung ultrasound (LUS) can assess ILD by the evaluation of B-lines, the sonographic sign of pulmonary interstitial involvement. RESEARCH QUESTION: To establish the prognostic value of B-lines in a large number of patients with SSc. STUDY DESIGN AND METHODS: A total of 396 consecutive patients with SSc, who were enrolled at three Rheumatology Departments, underwent a comprehensive LUS examination on the anterolateral and posterior chest for a total of 58 scanning sites. All available clinical, imaging, and functional data were recorded. Patients were followed after enrolment to establish the prognostic role of LUS. RESULTS: The median number of B-lines was higher in patients with the diffuse cutaneous subset (44 vs 17 B-lines; P < .0001), topoisomerase I autoantibodies (39 vs 16 B-lines; P < .0001), and the presence of ILD at chest high-resolution CT (45 vs 9 B-lines; P < .0001). At multivariable analysis, the number of posterior B-lines ≥5 was associated with new development or worsening ILD (hazard ratio, 3.378; 95% CI, 1.137-9.994; P = .028), with additional value over topoisomerase I positivity. The prognostic value was further confirmed in the subgroup of patients with known ILD at baseline (hazard ratio, 1.010; 95% CI, 1.003-1.018; P = .008). INTERPRETATION: Lung ultrasound B-lines are associated with worsening or development of pulmonary deterioration. In the near future, LUS might become part of the diagnostic and prognostic armamentarium in patients with SSc, which would allow a more sustainable and user-friendly approach to this very fragile population.

Measuring Cot-Side the Effects of Parenteral Nutrition on Preterm Cortical Function.

Early nutritional compromise after preterm birth is shown to affect long-term neurodevelopment, however, there has been a lack of early functional measures of nutritional effects. Recent progress in computational electroencephalography (EEG) analysis has provided means to measure the early maturation of cortical activity. Our study aimed to explore whether computational metrics of early sequential EEG recordings could reflect early nutritional care measured by energy and macronutrient intake in the first week of life. A higher energy or macronutrient intake was assumed to associate with improved development of the cortical activity. We analyzed multichannel EEG recorded at 32 weeks (32.4 ± 0.7) and 36 weeks (36.6 ± 0.9) of postmenstrual age in a cohort of 28 preterm infants born before 32 weeks of postmenstrual age (range: 24.3-32 weeks). We computed several quantitative EEG measures from epochs of quiet sleep (QS): (i) spectral power; (ii) continuity; (iii) interhemispheric synchrony, as well as (iv) the recently developed estimate of maturational age. Parenteral nutritional intake from day 1 to day 7 was monitored and clinical factors collected. Lower calories and carbohydrates were found to correlate with a higher reduction of spectral amplitude in the delta band. Lower protein amount associated with higher discontinuity. Both higher proteins and lipids intake correlated with a more developmental increase in interhemispheric synchrony as well as with better progress in the estimate of EEG maturational age (EMA). Our study shows that early nutritional balance after preterm birth may influence subsequent maturation of brain activity in a way that can be observed with several intuitively reasoned and transparent computational EEG metrics. Such measures could become early functional biomarkers that hold promise for benchmarking in the future development of therapeutic interventions.

Objective assessment of blinking and facial expressions in Parkinson's disease using a vertical electro-oculogram and facial surface electromyography.

OBJECTIVE: Hypomimia is a common and early symptom of Parkinson's disease (PD), which reduces the ability of PD patients to manifest emotions. Currently, it is visually evaluated by the neurologist during neurological examinations for PD diagnosis, as described in task 3.2 of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Since such an evaluation is semi-quantitative and affected by inter-variability, this paper aims to measure the physiological parameters related to eye blink and facial expressions extracted from a vertical electro-oculogram (VEOG) and facial surface electromyography (fsEMG) to differentiate PD patients from healthy control subjects (HCs). APPROACH: The spontaneous eye blink rate-minute (sEBR), its maximum amplitude (BMP), and facial cutaneous muscle activity were measured in 24 PD patients and 24 HCs while the subjects looked at a visual-tester composed of three main parts: static vision, dynamic vision and reading silently. Specificity and sensitivity for each parameter were calculated. MAIN RESULTS: The VEOG and the fsEMG allowed the identification of some parameters related to eye blink and facial expressions (i.e. sEBR, BMP, frontal and peribuccal muscular activities), being able to distinguish between PD patients and HCs with high sensitivity and specificity. SIGNIFICANCE: The demonstration that the combination of parameters related to eye blink and facial expressions can discriminate (with high accuracy) between PD patients versus HCs, thus resulting in a useful tool to support the neurologist in objective assessment of hypomimia for improving PD diagnosis.

Cardiac involvement by CMR in different genotypic groups of thalassemia major patients.

Beta thalassemia major (ß-TM) displays a great deal of phenotypic heterogeneity, not fully investigated in terms of cause-effect. We aimed to detect if different genotypic groups could be related to different levels of cardiac impairment, evaluated by cardiovascular magnetic resonance (CMR). We considered 671 ß-TM patients (age 30.1 years, 52.9% females) consecutively enrolled in the Myocardial Iron Overload (MIO) in Thalassemia network. MIO was assessed by T2* technique. Biventricular function was quantified by cine images. Myocardial fibrosis was evaluated by late gadolinium enhancement (LGE) technique. Three groups of patients were identified: heterozygotes ß+/ß° (N = 279), homozygotes ß + (N = 154), homozygotes ß° (N = 238). Transfusional needs resulted significantly lower in homozygous ß + TM patients when compared to the other groups. The homozygous ß + group versus the heterozygous and homozygous ß° groups showed higher global heart T2* values (P < 0.0001) and a lower number of patients with a global heart T2* value<20 ms (P < 0.001). The homozygotes ß + showed a lower number of patients with a pathological left ventricular ejection fraction (LVEF) than the other two groups (P < 0.05). The ß+/ß + TM patients showed less MIO and a concordant better systolic heart function. These data support the knowledge of different genotypic groups in the management of ß-TM patients.

Intracoronary Gene Delivery of the Cytoprotective Factor Vascular Endothelial Growth Factor-B167 in Canine Patients with Dilated Cardiomyopathy: A Short-Term Feasibility Study.

Dilated cardiomyopathy (DCM) is a myocardial disease of dogs and humans characterized by progressive ventricular dilation and depressed contractility and it is a frequent cause of heart failure. Conventional pharmacological therapy cannot reverse the progression of the disease and, in humans, cardiac transplantation remains the only option during the final stages of heart failure. Cytoprotective gene therapy with vascular endothelial growth factor-B167 (VEGF-B167) has proved an effective alternative therapy, halting the progression of the disease in experimental studies on dogs. The aim of this work was to test the tolerability and feasibility of intracoronary administration, under fluoroscopic guidance, of VEGF-B167 carried by adeno-associated viral vectors in canine DCM patients. Ten patients underwent the gene delivery procedure. The intraoperative phase was well tolerated by all dogs. Clinical and echocardiographic assessments at 7- and 30-days post-procedure showed stable conditions compared to the pre-procedure phase. The results of this work indicate that intracoronary VEGF-B167 gene delivery is feasible and tolerated in dogs with DCM. Further monitoring/investigations are ongoing to evaluate the effects of this therapy on disease progression.