Air pollution and out-of-hospital cardiac arrest risk: a 7-year study from a highly polluted area.

AIMS: Globally, nearly 20% of cardiovascular disease deaths were attributable to air pollution. Out-of-hospital cardiac arrest (OHCA) represents a major public health problem; therefore, the identification of novel OHCA triggers is of crucial relevance. The aim of the study was to evaluate the association between air pollution (short-, mid-, and long-term exposures) and OHCA risk, during a 7-year period in a highly polluted urban area in northern Italy, with a high density of automated external defibrillators (AEDs). METHODS AND RESULTS: Out-of-hospital cardiac arrests were prospectively collected from the 'Progetto Vita Database' between 1 January 2010 and 31 December 2017; day-by-day air pollution levels were extracted from the Environmental Protection Agency stations. Electrocardiograms of OHCA interventions were collected from the AED data cards. Day-by-day particulate matter (PM) 2.5 and 10, ozone (O3), carbon monoxide (CO), and nitrogen dioxide (NO2) levels were measured. A total of 880 OHCAs occurred in 748 days. A significant increase in OHCA risk with a progressive increase in PM2.5, PM10, CO, and NO2 levels was found. After adjustment for temperature and seasons, a 9% and 12% increase in OHCA risk for each 10 µg/m3 increase in PM10 (P < 0.0001) and PM2.5 (P < 0.0001) levels was found. Air pollutant levels were associated with both asystole and shockable rhythm risk, while no correlation was found with pulseless electrical activity. CONCLUSION: Short- and mid-term exposures to PM2.5 and PM10 are independently associated with the risk of OHCA due to asystole or shockable rhythm.

Organization and Activity of Italian Echocardiographic Laboratories: A Survey of the Italian Society of Echocardiography and Cardiovascular Imaging.

Background: The Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI) conducted a national survey to understand better how different echocardiographic modalities are used and accessed in Italy. Methods: We analyzed echocardiography laboratory activities over a month (November 2022). Data were retrieved via an electronic survey based on a structured questionnaire, uploaded on the SIECVI website. Results: Data were obtained from 228 echocardiographic laboratories: 112 centers (49%) in the northern, 43 centers (19%) in the central, and 73 (32%) in the southern regions. During the month of observation, we collected 101,050 transthoracic echocardiography (TTE) examinations performed in all centers. As concern other modalities there were performed 5497 transesophageal echocardiography (TEE) examinations in 161/228 centers (71%); 4057 stress echocardiography (SE) examinations in 179/228 centers (79%); and examinations with ultrasound contrast agents (UCAs) in 151/228 centers (66%). We did not find significant regional variations between the different modalities. The usage of picture archiving and communication system (PACS) was significantly higher in the northern (84%) versus central (49%) and southern (45%) centers (P < 0.001). Lung ultrasound (LUS) was performed in 154 centers (66%), without difference between cardiology and noncardiology centers. The evaluation of left ventricular (LV) ejection fraction was evaluated mainly using the qualitative method in 223 centers (94%), occasionally with the Simpson method in 193 centers (85%), and with selective use of the three-dimensional (3D) method in only 23 centers (10%). 3D TTE was present in 137 centers (70%), and 3D TEE in all centers where TEE was done (71%). The assessment of LV diastolic function was done routinely in 80% of the centers. Right ventricular function was evaluated using tricuspid annular plane systolic excursion in all centers, using tricuspid valve annular systolic velocity by tissue Doppler imaging in 53% of the centers, and using fractional area change in 33% of the centers. When we divided into cardiology (179, 78%) and noncardiology (49, 22%) centers, we found significant differences in the SE (93% vs. 26%, P < 0.001), TEE (85% vs. 18%), UCA (67% vs. 43%, P < 0001), and STE (87% vs. 20%, P < 0.001). The incidence of LUS evaluation was similar between the cardiology and noncardiology centers (69% vs. 61%, P = NS). Conclusions: This nationwide survey demonstrated that digital infrastructures and advanced echocardiography modalities, such as 3D and STE, are widely available in Italy with a notable diffuse uptake of LUS in the core TTE examination, a suboptimal diffusion of PACS recording, and conservative use of UCA, 3D, and strain. There are significant differences between northern and central-southern regions and echocardiographic laboratories that pertain to the cardiac unit. This inhomogeneous distribution of technology represents one of the main issues that must be solved to standardize the practice of echocardiography.

Stress Echocardiography in Italian Echocardiographic Laboratories: A Survey of the Italian Society of Echocardiography and Cardiovascular Imaging.

Background: The Italian Society of Echography and Cardiovascular Imaging (SIECVI) conducted a national survey to understand the volumes of activity, modalities and stressors used during stress echocardiography (SE) in Italy. Methods: We analyzed echocardiography laboratory activities over a month (November 2022). Data were retrieved through an electronic survey based on a structured questionnaire, uploaded on the SIECVI website. Results: Data were obtained from 228 echocardiographic laboratories, and SE examinations were performed in 179 centers (80.6%): 87 centers (47.5%) were in the northern regions of Italy, 33 centers (18.4%) were in the central regions, and 61 (34.1%) in the southern regions. We annotated a total of 4057 SE. We divided the SE centers into three groups, according to the numbers of SE performed: <10 SE (low-volume activity, 40 centers), between 10 and 39 SE (moderate volume activity, 102 centers) and ≥40 SE (high volume activity, 37 centers). Dipyridamole was used in 139 centers (77.6%); exercise in 120 centers (67.0%); dobutamine in 153 centers (85.4%); pacing in 37 centers (21.1%); and adenosine in 7 centers (4.0%). We found a significant difference between the stressors used and volume of activity of the centers, with a progressive increase in the prevalence of number of stressors from low to high volume activity (P = 0.033). The traditional evaluation of regional wall motion of the left ventricle was performed in all centers, with combined assessment of coronary flow velocity reserve (CFVR) in 90 centers (50.3%): there was a significant difference in the centers with different volume of SE activity: the incidence of analysis of CFVR was significantly higher in high volume centers compared to low - moderate - volume (32.5%, 41.0% and 73.0%, respectively, P < 0.001). The lung ultrasound (LUS) was assessed in 67 centers (37.4%). Furthermore for LUS, we found a significant difference in the centers with different volume of SE activity: significantly higher in high volume centers compared to low - moderate - volume (25.0%, 35.3% and 56.8%, respectively, P < 0.001). Conclusions: This nationwide survey demonstrated that SE was significantly widespread and practiced throughout Italy. In addition to the traditional indication to coronary artery disease based on regional wall motion analysis, other indications are emerging with an increase in the use of LUS and CFVR, especially in high-volume centers.

Estimated EEG functional connectivity and aperiodic component induced by vagal nerve stimulation in patients with drug-resistant epilepsy.

Background: Vagal nerve stimulation (VNS) improves seizure frequency and quality of life in patients with drug-resistant epilepsy (DRE), although the exact mechanism is not fully understood. Previous studies have evaluated the effect of VNS on functional connectivity using the phase lag index (PLI), but none has analyzed its effect on EEG aperiodic parameters (offset and exponent), which are highly conserved and related to physiological functions. Objective: This study aimed to evaluate the effect of VNS on PLI and aperiodic parameters and infer whether these changes correlate with clinical responses in subjects with DRE. Materials and methods: PLI, exponent, and offset were derived for each epoch (and each frequency band for PLI), on scalp-derived 64-channel EEG traces of 10 subjects with DRE, recorded before and 1 year after VNS. PLI, exponent, and offset were compared before and after VNS for each patient on a global basis, individual scalp regions, and channels and separately in responders and non-responders. A correlation analysis was performed between global changes in PLI and aperiodic parameters and clinical response. Results: PLI (global and regional) decreased after VNS for gamma and delta bands and increased for an alpha band in responders, but it was not modified in non-responders. Aperiodic parameters after VNS showed an opposite trend in responders vs. non-responders: both were reduced in responders after VNS, but they were increased in non-responders. Changes in aperiodic parameters correlated with the clinical response. Conclusion: This study explored the action of VNS therapy from a new perspective and identified EEG aperiodic parameters as a new and promising method to analyze the efficacy of neuromodulation.

Scorepochs: A Computer-Aided Scoring Tool for Resting-State M/EEG Epochs.

M/EEG resting-state analysis often requires the definition of the epoch length and the criteria in order to select which epochs to include in the subsequent steps. However, the effects of epoch selection remain scarcely investigated and the procedure used to (visually) inspect, label, and remove bad epochs is often not documented, thereby hindering the reproducibility of the reported results. In this study, we present Scorepochs, a simple and freely available tool for the automatic scoring of resting-state M/EEG epochs that aims to provide an objective method to aid M/EEG experts during the epoch selection procedure. We tested our approach on a freely available EEG dataset containing recordings from 109 subjects using the BCI2000 64 channel system.

On the Variability of Functional Connectivity and Network Measures in Source-Reconstructed EEG Time-Series.

The idea of estimating the statistical interdependence among (interacting) brain regions has motivated numerous researchers to investigate how the resulting connectivity patterns and networks may organize themselves under any conceivable scenario. Even though this idea has developed beyond its initial stages, its practical application is still far away from being widespread. One concurrent cause may be related to the proliferation of different approaches that aim to catch the underlying statistical interdependence among the (interacting) units. This issue has probably contributed to hindering comparisons among different studies. Not only do all these approaches go under the same name (functional connectivity), but they have often been tested and validated using different methods, therefore, making it difficult to understand to what extent they are similar or not. In this study, we aim to compare a set of different approaches commonly used to estimate the functional connectivity on a public EEG dataset representing a possible realistic scenario. As expected, our results show that source-level EEG connectivity estimates and the derived network measures, even though pointing to the same direction, may display substantial dependency on the (often arbitrary) choice of the selected connectivity metric and thresholding approach. In our opinion, the observed variability reflects the ambiguity and concern that should always be discussed when reporting findings based on any connectivity metric.

Three-dimensional echocardiography in various types of heart disease: a comparison study of magnetic resonance imaging and 64-slice computed tomography in a real-world population.

BACKGROUND: Accurate quantification of left ventricular (LV) volumes [end-diastolic volume (EDV) and end-systolic volume (ESV)] and ejection fraction (EF) is of critical importance. The development of real-time three-dimensional echocardiography (RT3DE) has shown better correlation than two-dimensional (2D) echocardiography with magnetic resonance imaging (MRI) measurements. The aim of our study was to assess the accuracy of RT3DE and 64-slice computed tomography (CT) in the evaluation of LV volumes and function using MRI as the reference standard in a real-world population with various types of heart disease with different chamber geometry. METHODS: The study population consisted of 66 patients referred for cardiac MRI for various pathologies. All patients underwent cardiac MRI, and RT3DE and 64 slices CT were then performed on a subsequent day. The study population was then divided into 5 clinical groups depending on the underlying heart disease. RESULTS: RT3DE volumes correlated well with MRI values (R 2 values: 0.90 for EDV and 0.94 for ESV). RT3DE measurements of EF correlated well with MRI values (R 2 = 0.86). RT3DE measurements resulted in slightly underestimated values of both EDV and ESV, as reflected by biases of -9.18 and -4.50 mL, respectively. Comparison of RT3DE and MRI in various types of cardiomyopathies showed no statistical difference between different LV geometrical patterns. CONCLUSION: These results confirm that RT3DE has good accuracy in everyday clinical practice and can be of clinical utility in all types of cardiomyopathy independently of LV geometric pattern, LV diameter or wall thickness, taking into account a slight underestimation of LV volumes and EF compared to MRI.

Myeloperoxidase-Related Chlorination Activity Is Positively Associated with Circulating Ceruloplasmin in Chronic Heart Failure Patients: Relationship with Neurohormonal, Inflammatory, and Nutritional Parameters.

RATIONALE: Heart failure (HF) is accompanied by the development of an imbalance between oxygen- and nitric oxide-derived free radical production leading to protein nitration. Both chlorinating and peroxidase cycle of Myeloperoxidase (MPO) contribute to oxidative and nitrosative stress and are involved in tyrosine nitration of protein. Ceruloplasmin (Cp) has antioxidant function through its ferroxidase I (FeOxI) activity and has recently been proposed as a physiological defense mechanism against MPO inappropriate actions. OBJECTIVE: We investigated the relationship between plasma MPO-related chlorinating activity, Cp and FeOxI, and nitrosative stress, inflammatory, neurohormonal, and nutritional biomarkers in HF patients. METHODS AND RESULTS: In chronic HF patients (n = 81, 76 ± 9 years, NYHA Class II (26); Class III (29); Class IV (26)) and age-matched controls (n = 17, 75 ± 11 years, CTR), plasma MPO chlorinating activity, Cp, FeOxI, nitrated protein, free Malondialdehyde, BNP, norepinephrine, hsCRP, albumin, and prealbumin were measured. Plasma MPO chlorinating activity, Cp, BNP, norepinephrine, and hsCRP were increased in HF versus CTR. FeOxI, albumin, and prealbumin were decreased in HF. MPO-related chlorinating activity was positively related to Cp (r = 0.363, P < 0.001), nitrated protein, hsCRP, and BNP and inversely to albumin. CONCLUSIONS: Plasma MPO chlorinated activity is increased in elderly chronic HF patients and positively associated with Cp, inflammatory, neurohormonal, and nitrosative parameters suggesting a role in HF progression.

Low serum ferroxidase I activity is associated with mortality in heart failure and related to both peroxynitrite-induced cysteine oxidation and tyrosine nitration of ceruloplasmin.

RATIONALE: Ceruloplasmin antioxidant function is mainly related to its ferroxidase I (FeOxI) activity, which influences iron-dependent oxidative and nitrosative radical species generation. Peroxynitrite, whose production is increased in heart failure (HF), can affect ceruloplasmin antioxidant function through amino acid modification. OBJECTIVE: We investigated the relationship between FeOxI and ceruloplasmin tyrosine and cysteine modification and explored in a cohort of patients with HF the potential clinical relevance of serum FeOxI. METHODS AND RESULTS: In patients with chronic HF (n=96, 76 ± 9 years; New York Heart Association class, 2.9 ± 0.8) and age-matched controls (n=35), serum FeOxI, FeOxII, ceruloplasmin, nitrotyrosine-bound ceruloplasmin, B-type natriuretic peptide, norepinephrine, and high-sensitivity C-reactive protein were measured, and the patients were followed up for 24 months. Ceruloplasmin, B-type natriuretic peptide, norepinephrine, and high-sensitivity C-reactive protein were increased in HF versus controls. FeOxI was decreased in HF (-20%) and inversely related to nitrotyrosine-bound ceruloplasmin (r, -0.305; P=0.003). In HF, FeOxI lower tertile had a mortality rate doubled compared with middle-higher tertiles. FeOxI emerged as a mortality predictor (hazard ratio, 2.95; 95% confidence intervals [1.29-6.75]; P=0.011) after adjustment for age, sex, hypertension, smoking, sodium level, estimated glomerular filtration rate, and high-sensitivity C-reactive protein. In experimental settings, peroxynitrite incubation of serum samples and isolated purified ceruloplasmin reduced FeOxI activity while increasing ceruloplasmin tyrosine nitration and cysteine thiol oxidation. Reduced glutathione prevented peroxynitrite-induced FeOxI drop, tyrosine nitration, and cysteine oxidation; flavonoid(-)-epicatechin, which prevented ceruloplasmin tyrosine nitration but not cysteine oxidation, partially impeded peroxynitrite-induced FeOxI drop. CONCLUSIONS: Reduced activity of serum FeOxI is associated with ceruloplasmin nitration and reduced survival in patients with HF. Both ceruloplasmin tyrosine nitration and cysteine thiol oxidation may be operant in vivo in peroxynitrite-induced FeOxI activity inhibition.

Retrospective study on the benefits of combined Memantine and cholinEsterase inhibitor treatMent in AGEd Patients affected with Alzheimer's Disease: the MEMAGE study.

BACKGROUND: Combined therapy of memantine and acetylcholinesterase inhibitors (AChEIs) in patients with Alzheimer's disease (AD) may be associated with higher benefits than either monotherapy. OBJECTIVE: This retrospective multicentric study conducted in seven Italian Ambulatory Centers for Dementia assessed the efficacy and safety of memantine 20 mg/day administered for 6 months in addition to an AChEI in AD patients with worsened cognitive functions and behavioral disorders. METHODS: A total number of 240 patients (61.7% of women, 38.3% men, mean age 77.9 ± 7.32 years old) who had started treatment with the combination therapy were recruited. At baseline (T0), Month 3 (T1), and Month 6 (T2), cognitive functions were assessed by Mini-Mental State Examination (MMSE), functional dependence by activities of daily living (ADL) and instrumental ADL, behavioral disturbances by the Neuropsychiatric Inventory (NPI), and comorbidities by Cumulative Illness Rating Scale. Adverse events were reported during the study. RESULTS: MMSE total score significantly increased at Month 6 (p = 0.029 versus month 3) and IADL total score significantly decreased from baseline to endpoint (p = 0.033). There were no significant changes from baseline in mean ADL, despite significant improvements in NPI total score. The mean MMSE total score significantly increased with the combination donepezil + memantine compared to rivastigmine + memantine. The adverse events profile was in line with the expected range of the drugs studied and concomitant therapies. Overall, 17 patients discontinued treatment in the observation time. CONCLUSION: Combined treatment with memantine and AChEIs was effective in patients with AD, particularly in slowing cognitive impairment and preventing the onset of agitation and aggression in elderly AD patients.

Hem-o-lok clips to control both the artery and the vein during laparoscopic nephrectomy: personal experience and review of the literature.

BACKGROUND AND PURPOSE: Control and division of the renal vessels is a critical step in laparoscopic nephrectomy. Although the linear cutting stapler is easy to use, a 1.7% malfunction rate has been reported, and the consequences of this failure can be serious, including often-emergency conversion to an open procedure and even death. We reviewed the purely laparoscopic nephrectomies performed in our center, in which both the renal artery and the vein were secured using only nonabsorbable polymer ligating (NPL) clips. Our purpose was to evaluate the reliability, safety, and cost-effectiveness of this surgical approach. PATIENTS AND METHODS: We retrospectively reviewed our 31 laparoscopic nephrectomies performed from November 2002 to November 2005. In all the procedures, both the renal artery and the renal vein were secured using only NPL clips. For each patient, the operative time, estimated blood loss, early and late complications, and length of hospital stay were analyzed. Further, we performed a MEDLINE search for laparoscopic nephrectomies in which both the renal artery and the vein were secured using only Hem-o-lok clips. RESULTS: No renal vessel injuries, cases of clip dislodgement or slippage, or bleeding were recorded. Worthy of note, we achieved a meaningful reduction in the cost per procedure. To the best of our knowledge, renal-pedicle control exclusively with Hem-o-lok clips during purely laparoscopic nephrectomy has not been yet published. CONCLUSIONS: Any device or technique for vascular control is prone to malfunction in either open or laparoscopic surgery. The described approach is safe, reliable, rapid, and inexpensive.

Multicenter study on the use of gemcitabine to prevent recurrence of multiple-recurring superficial bladder tumors following intravesical antiblastic agents and/or BCG: evaluation of tolerance.

OBJECTIVES: The treatment of choice for superficial bladder TCC is endoscopic resection, followed or not by intravesical immuno/chemotherapy. Some patients are not responders to common intravesical therapy and are more exposed to disease progression. In this case the suitable treatment is radical cystectomy. Because gemcitabine is effective against advanced bladder cancer, we have initiated a study to evaluate the efficacy of its intravesical use to prevent relapse and disease progression, and tolerance and safety of this drug in patients with multi-treated bladders. In this preliminary study, we cite only data on tolerance. MATERIALS AND METHODS: 64 patients were selected, and 61 were evaluable (age range 39-84 years), with multiple-recurrent bladder TCC. All patients were previously treated with intravesical chemotherapy and/or immunotherapy. The protocol provided for intravesical instillation of gemcitabine (2000 mg) once per week for 8 weeks. We collected data regarding problems noted by the patients (both local and systemic). RESULTS: 53 patients out of 61 (86.9%) completed the cycle. Side effects appeared in 14 patients, 8 of these had to suspend the treatment. Severe side effects were systemic in 4 patients (1 systemic edema, 1 malaise and dysgeusia, 1 hyperthermia and severe strangury, 1 elevated transaminases and asthenia), and local in 4 patients (1 severe urinary urgency, 1 hematuria, 1 urinary incontinence, and 1 case of pelvic pain). In 6 patients we observed pelvic pain, hematuria, strangury and UTI of medium magnitude that did not require treatment interruption. CONCLUSIONS: We believe that the severe side effects requiring treatment interruption are attributable primarily to increased sensitivity in patients with multi-treated bladders. In our experience, the side effects responsible for suspension occurred at the start of treatment in 7 cases out of 8. Our study demonstrates the safety of intravesical gemcitabine in patients with recurrent and multi-treated superficial TCC of the bladder.

Penile metastasis from primary transitional cell carcinoma of the renal pelvis: first manifestation of systemic spread.

BACKGROUND: Almost one-third of all penile metastases are detected at the same time as a primary tumor, whereas the remaining two-thirds are detected a mean of 18 months after the discovery of the primary tumor. Cutaneous metastasis of transitional cell carcinoma (TCC) is extremely rare and generally accepted as the late manifestation of a systemic spread. CASE PRESENTATION: We report the first case of simultaneous penile and lung metastases from a primary TCC of the renal pelvis in a 76-year-old man, that occurred 8 years after a left nephroureterectomy. CONCLUSIONS: This case report underscores the importance of physical examinations of the skin of patients who undergo surgical procedures for TCC from bladder as well as from the upper urinary tract, including those seemingly without metastatic disease, because of the possibility of skin and penile metastatic spread.