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Maurizio Ferri

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The COVID-19 pandemic represents one of the greatest public health crises in recent history that caused unprecedented and massive disruptions of social and economic life globally. It is widely acknowledged that bats are the animal reservoir of coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2), the causative agent of the human coronavirus disease 2019 (COVID-19). It has also long been known that coronaviruses circulate among different animal species. However, much remain to be understood of the epidemiology, the presumed existence of intermediate animal species and current and potential animal routes of SARS-Cov-2 transmission to humans. The recent observational and experimental studies also highlight the role of domestic and farmed animals in the epidemiology of COVID-19. This raises concerns of the potential spread of infection among susceptible animal species, with the risk of evolving into panzootic, and the likely occurrence of anthropozoonoses or reverse zoonosis (from humans to animals). As for other wildlife emerging pathogens, the animal-human spillover of SARS-CoV-2 is linked to a closer interface with humans, with the resulting risk of a pandemic. This knowledge has meaningful implications for the design of effective wildlife animal surveillance (epidemic intelligence) targeting CoVs in animal reservoirs, and requires the mobilization of different lines of expertise, notably veterinary epidemiologists and virologists, within a multi-disciplinary approach according to the One-Health principles.

Ning Zhang

and 5 more

Atrioventricular node ablation (AVNA) combined with His bundle pacing (HBP) are feasible, safe, and effective in patients with refractory atrial fibrillation (AF), however, the pacing parameters of sensing and capture threshold maybe sometimes unsatisfactory. Left bundle branch pacing (LBBP) provides obvious advantage in patients with conduction diseases at the distal His bundle for its better sensing, a lower and more stable capture threshold. Among hypertrophic cardiomyopathy (HCM) patients, AF is a common sustained arrhythmia, primarily caused by left atrial dilatation and remodeling. Few is known about the feasibility of electrophysiological performance, safety and clinical effectiveness of atrioventricular junction ablation (AVJA) combined with LBBP in patient with refractory AF and HCM. Here, we report a case of a 56-year-old woman suffering from refractory AF and HCM, however HBP was failed for its unsatisfactory sensing, a high and unstable capture threshold for her, therefore, ablation and LBBB were accepted by her to achieve better rate control. Improvement in symptoms, quality of life, and exercise capacity has been observed during the 1.5-year follow-up. To our knowledge, our case originally confirmed that the combination of AVJA and LBBP, without the defect of AVNA combined with HBP, is a better strategy with feasibility and safety for refractory AF patients with comorbidity of HCM, additionally, it may make LBBP more applicable and valuable among patients suffering from HCM meanwhile pace maker treatments are essential.

Dalibor Kurepa

and 3 more

Abstract Background: Nasal CPAP introduces positive pressure of air into both trachea and stomach, which may affect gastric emptying. The rate of gastric emptying can be estimated by US by two validated techniques: “antral cross-sectional area” (2-dimensional estimate of the surface area at the gastric antrum), and “spheroid gastric volume” (3-dimensional estimate of the stomach content volume). No study examined gastric emptying rate in infants on bubble CPAP (bCPAP). Objective: To compare gastric emptying rates in neonates on machine-derived nasal CPAP (MD-nCPAP) with those on bCPAP. Methods: Ultrasound measurements of the amount of milk in the stomach were performed before feeding and at 1, 2, and 3 hours after the start of feeding, using both the ACSA and spheroid methods. Rates of gastric emptying were calculated during the “early” (1-2 hours) and “late” (2-3 hours) phases after feeding. Results: We recruited 32 infants (25-34 weeks gestational age). Seventeen infants were treated with MD-nCPAP [median birth weight 1015 g (IQR: 870 to 1300), gestational age 28 weeks (IQR: 27 to 29), postnatal age 20 days (IQR: 14 to 28)], while 15 infants were treated with bCPAP [median birth weight 960 g (IQR: 855 to 1070), gestational age 27 weeks (IQR: 26 to 28), postnatal age 17 days (IQR: 15 to 25)]. Gastric emptying rates (% emptied/min) were significantly faster in the “early” compared to the “late” phase for all infants. There were no significant differences in the rates of gastric emptying (either “early” or “late”) or volumes of gastric residuals between infants receiving MD-nCPAP or bCPAP, measured by either method. Conclusions: Gastric emptying is faster during the “early” compared to the “late” phase. Gastric emptying rates are not different in infants receiving MD-nCPAP vs bCPAP.

Wendy Bower

and 5 more

Objective Post-menopausal nocturia is poorly understood. This study aimed to identify hormonal and lifestyle factors associated with nocturia and to understand the relative contribution of altered urine production and bladder storage dysfunction in women. Design, setting, population and methods Women ≥40 years presenting to public continence services were enrolled in a cross-sectional study. 153 participants completed a hormone status questionnaire, a validated nocturia causality screening tool and a 3-day bladder diary. Descriptive statistics and logistic regression models for nocturia severity and bladder diary parameters were computed. Results Overall, 91.5 % reported nocturia, 55% ≥2 /night. There was a difference of 167.5 mL (p<0.001) in nocturnal urine volume between women with nocturia ≥2 (median 736mL) vs less often (517mL). Significant predictors of self-reported disruptive nocturia were age (OR 1.04, 95%CI 1.002-1.073) and vitamin D supplementation (OR 2.33, 95%CI 1.11-4.91). Nocturnal polyuria was significantly more common with nocturia ≥2 compared to less often (p<0.002). 150 minutes of exercise per week was protective for nocturnal polyuria (OR 0.22, p=0.001). Nocturia index >1.3 was significantly predicted by age (OR 1.07, p<0.001), regular exercise (OR 0.41, p=0.036), day flushes (OR 4.00, p=0.013) and use of Vitamin D (OR 2.34, p=0.043). Maximum voided volumes were significantly lower with nocturia≥2 vs less often (night: 268ml vs 350mL; day: 200mL vs 290mL). Conclusions Bothersome nocturia in post-menopausal women is associated with changes to both nocturnal diuresis and bladder storage. Regular physical activity, prolapse reduction and oestrogen replacement may be adjunctive in managing bothersome nocturia in women.

Maria Papadaki

and 4 more

Objective: Τo investigate the association of serum vitamin D and nasal secretion antimicrobial peptides (AMPs) levels with the severity of acute bronchiolitis. Study design: We conducted a prospective single pediatric tertiary care center cohort study of inpatients aged 0-18 months with a first episode of acute bronchiolitis from November 1st 2014 to April 30th 2017. Disease severity was determined by the length of hospitalization and supplemental hospital data. Qualitative measurements included serum 25(OH)D and nasal secretion LL-37 and β-defensin-2 levels. Correlations were examined with the Mann-Whitney and Kruskal-Wallis criteria for qualitative and the correlation coefficient Spearman’s rho for quantitative factors. Multiple linear and logarithmic regression were performed in order to adjust for confounding factors. Results: The study population consisted of 153 infants and toddlers with mean age 3.6 months (SD: +2.8). The median level of serum 25(OH)D was 51.4 nmol/L (IQR: 29.7-72.2). No association was found between serum 25(OH)D and AMPs nasal secretions levels. Serum 25(OH)D and nasal secretion β-defensin-2 levels were not associated with the severity of bronchiolitis. In contrast, LL-37 levels were inversely associated with the length of hospitalization (rho = -0.340, p = 0.001) and the need for medication use (p = 0.001) and this association remained significant after adjustment for potential confounders. Conclusion: A significant association between LL-37 nasal secretions levels with the severity of acute bronchiolitis was found in hospitalized infants and toddlers. The role of LL-37 in the pathogenesis of bronchiolitis merits further investigation.

Giovanni Rossi

and 4 more

The immunopathology of respiratory syncytial virus (RSV) infection, the most common cause of lower respiratory tract infections (LRTI) in the pediatric population, with severe disease being the exception. The variability of the clinical presentation is incompletely explained by host, viral and environmental factors but, in infants and young children, disease severity is certainly linked to the physiological immune immaturity. There is evidence that the maturation of the host immune response is, at least in part, promoted by the composition of the nasopharyngeal microbiome that, modulating excessive inflammation, can counteract the predisposition to develop viral respiratory infections and lower the risk of disease severity. However, interaction between the nasopharyngeal microbiota and respiratory viruses can be bidirectional. Microbial dysbiosis can drive disease pathogenesis but may also represents a reflection of the disease-induced alterations of the local milieu. Moreover, viruses like RSV, can also increase the virulence of potential pathogens in nasopharynx, which is a main reservoir of bacteria, and therefore promote their spread to the lower airways causing superinfection. Negative changes in microbial community composition in early life may constitute a heightened risk towards severe RSV respiratory infection and bacterial superinfection, whilst specific groups of microorganisms can be associated with protection. A better understanding into the potential negative and positive role of the different nasopharyngeal bacterial species in disease prevention as well as into the possible benefits of microbiome therapeutic manipulation, may improve patient outcomes.

Emily Barsky

and 3 more

Background: Medical care has shifted from a paternalistic model towards one centered around patient autonomy and shared decision-making (SDM), yet the role of the pediatric patient in decision-making is unclear. Studies suggest that many children with chronic disease are capable of participating in and even making medical decisions at a young age, and yet we do not standardly involve them. Methods: This is a single center survey study investigating physician attitudes towards involvement of children in decisions regarding lung transplantation, utilizing a hypothetical case scenario with systematic manipulation of age and maturity level. We evaluated physician belief regarding ultimate decision-making authority, attempts at reconciliation of parent-child discordance, and views towards utilizing ethics and psychiatry consultation services. Results: The majority of pediatric pulmonologists believe decision-making authority rests with the parents. The effects of age and maturity are unclear. In instances of parent-child disagreement, physician are more likely to try to convince parents to defer to the child if the child is both older and more mature. Physicians are divided on the utility of ethics and psychiatry consultations. Conclusion: Involvement of children in shared decision-making is broadly supported but poorly implemented. Despite evidence that children with chronic disease may have decisional capacity starting at a young age, the majority of physicians still grant decisional authority to parents. There are numerous barriers to involving children in decisions, including legal considerations. The role of age and maturity level in influencing these decisions appears small and warrants further investigation.

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The sinoatrial node in medication-resistant inappropriate sinus tachycardia: to modify or to ablate?Khalil El Gharib1*1Hôtel-Dieu de France, Beirut, Lebanon*Author for correspondence: khalil.gharib@outlook.comKEYWORDS: IST, sinus node modification, sinus node ablation, radiofrequency ablation, surgical ablationNo conflict of interest to discloseFunding: noneInappropriate sinus tachycardia (IST) is defined as a resting heart rate >100 beats per minute (with a mean heart rate >90 beats per minute over 24 hours) associated with highly symptomatic palpitations(1). The syndrome is associated neither with structural heart disease nor with any secondary cause of sinus tachycardia(2) and evidence suggests that enhanced intrinsic automaticity of the sinoatrial node, which can be due to anti-β-adrenergic antibodies, is behind its genesis(3). However, it is benign in terms of clinical outcomes and echocardiographic evidence of ventricular dysfunction(4), being rarely associated with tachycardia-induced cardiomyopathy(3).Patients with IST are essentially treated with ß-blockers to alleviate their symptoms(5). Ivabradine, a drug that inhibits funny calcium channels, particularly abundant in the SA node, showed modest benefit, receiving class IIa recommen­dation in the treatment of IST(4). But, the duration of medical therapy might be indefinite, and, a considerable number of patients would respond inadequately, or have no response, even after prolonged therapy(5). Historically, such patients would have subtotal right atrial excision, atrioventricular junctional ablation with permanent pacemaker implantation, or chemical occlusion of the sinus node artery(6). These options are considered today unacceptable in this setting, and other therapeutic approaches should be unveiled when resistance to medical treatment appears.Electrophysiological study was initially purely diagnostic, but recent advances in technology have allowed us to intervene(7); patients with ventricular and supraventricular tachyarrhythmias are successfully treated with percutaneous catheter procedures. Of these, SA node ablation/ modification has been proposed as alternative approaches in IST that is not responding to medical treatment; trials reported auspicious results, highlighted here.Electrophysiologic mapping to the site of the earliest endocardial activation during either spontaneous sinus tachycardia or isoproterenol-induced sinus tachycardia has rendered these procedures feasible(8). Additionally, combination with intracardiac echocardiography permitted a more accurate electrophysiologic and anatomic localization of the sinoatrial node(9).Sinus node modification is not a focal ablation, but requires complete abolition of the cranial portion of the SA node complex, the one that exhibits the most of the autonomic activity(9). It is defined as successful when the heart rate decreases by 30 beats per minute (bpm) during isoproterenol infusion(8). Short-term success was also defined by other investigators when there was a reduction of the baseline sinus rate to less than 90 bpm and the sinus rate during isoproterenol infusion by more than 20% or by 25%(8). The acute success rate for modification has been varying between 76 and 100 % across trials, while long-term clinical outcomes are modest at best, with reported freedom from IST ranging from 23 to 85%(10).Complications specific to SA node modification include superior vena cava (SVC) syndrome, diaphragmatic paralysis, and sinus node dysfunction(10). And while modification with conventional methods has its setbacks, modification using laser energy can be considered in the setting of IST. This modality creates clear-cut homogenous transmural lesions of the myocardium that comprises the scattered “functional” SA node(11). The burnt myocardium will then heal into a dense fibrous scar, decreasing potential amplitudes. And when adapting laser energy settings to the thickness of the myocardial wall, collateral dam­ages such as esophageal fistulae, lung burns, and phrenic nerve palsy will be avoided(11); thus, this technique may prove itself as a new intriguing alternative for the safe and effective treatment of IST.SA node modification is apt in achieving acute reductions in postprocedural heart rate. However, and as aforementioned, success rates are suboptimal in terms of symptomatic control with a significant recurrence rate(12). Catheter ablation aiming at either total exclusion and obliteration of the SA node has been described and performed, success being defined as a slowing of >50% from the baseline rate of tachycardia along with a junctional escape rhythm(12). With radiofrequency (RF) applications, the earliest local atrial activation time would shift from a cranial location to a more caudal one, usually at the mid-lateral right atrium(5). Reviews have reported that acute success rates were consistently to be as high as 88.9%, with an overall frequency of recurrence of 19.6%, the latter occurring within a wide range of post-ablation intervals, anywhere from a few weeks to several months after the procedure(12). Additionally, Takemoto and colleagues documented a significant drop in B-type natriuretic peptide levels, 6 to 12 months after ablation, suggesting fewer stretching shears on cardiac muscle.Two types of response of the sinus tachycardia to RFA were observed across studies, whether a step-wise reduction in sinus rate accompanying migration of the site of earliest atrial activation in a cranial-caudal direction along the lateral right atrial wall, or an abrupt drop in heart rate in response to RFA at a focal site of earliest atrial activation(13).However, RFA of inappropriate sinus tachycardia requires a large number of applications of radiofrequency energy and is, as in SA node modification, associated with a high recurrence rate(13). Complete remission is achieved only in approximately 50% of patients in some studies(14); longer history of IST and those reporting near syncope/syncope having a higher probability of recurrence(15).While other studies have shown that RF ablation of the SA node can achieve even longer-term reductions in the sinus rate and relief of symptoms in two-thirds of patients with drug-refractory, inappropriate sinus tachycardia(13), aiming specific sites related to the SA node should be elaborated, for better and optimal outcomes Killu and colleagues created a lesion in the arcuate ridge resulting in complete abolition of the tachycardia, since arrhythmias arising in this region may exhibit both electrocardiographic and clinical similarities to IST(16). This has led to consider ablation of the arcuate ridge as a treatment of refractory IST, necessitating larger trials to confirm its potential role.Phrenic nerve injury is a severe and dreaded complication of SN ablation(12). Pericarditis, right diaphragmatic paralysis, and SVC syndrome are other undesirable side effects of the procedures, variously reported in studies. but a common complication was observed in them all, atrial tachyarrhythmias(12). It has been hypothesized that myocardial pathology, such as inflammation and fibrosis, considered iatrogenic due to the ablation procedures, may be promoting arrhythmias both in the region of the SA node, as well as in remote locations(12). Through multivariable analysis, higher resting heart rates post-ablation and smaller cranial-to-caudal shifts have been defined as predictors of atrial arrhythmias(15). In conclusion, catheter ablation could be considered an effective treatment for highly symptomatic, drug-refractory patients, even for those who did not respond to SA node modification(5).The sinus node is located close to the epicardial surface and catheter-based ablations do not always make full-thickness lesions across the atrial muscle, leading to failure of the ablation(17), besides the numerous trabeculae and the widely variable anatomy.Surgical ablation is not a first-line or routine management strategy for IST, but it has been proposed when IST resists or recurs after SN modification/ endocardial ablation(17). Effectively, in several studies, epicardial lesions, through a single small incision in one of the intercostal spaces, successfully slowed heart rate and shifted activation to a more caudal location, and surprisingly, subsequent endocardial lesions led to an even greater drop in heart rate and more caudal site of earliest activation(18). These outcomes were again replicated when using minimally invasive thoracoscopic ablation of the epicardial site of the SA node, concluding of the promising efficacy and the safety of this approach, since it preserves the phrenic nerve(17), although continued follow-up after surgery is required.Medication-resistant IST remains a medical challenge for physicians and cardiologists; and in the era of great advances in interventional cardiology, its treatment remains debatable. Sinus node modification/ ablation is not recommended as first-line therapy in IST, this procedure should be considered only in drug-refractory patients who have severe symptoms(13). Although the number of patients in the available studies is generally small, both procedures have documented an encouraging success rate in the short-term, while being less impressive in the long-term. It has been hypothesized that this discrepancy is due to the relatively large potential area of atrial pacemaker cells(18); modification or ablation may fail to ablate or isolate all the pathways that comprise the functional SA node because they often target the anatomic part and the area of earliest atrial activation(19). Others have explained that the long-term slowing in rhythm fails because these procedures inconsistently produce transmural lesions in the right atrium. Surgical treatment of IST has proposed a solution to the latter conflict when isolating the SA node with a wide cuff of surrounding atrial muscle(19). And with the advent of bipolar RF clamps and minimally invasive cardiac surgical techniques with thoracoscopic guidance, this approach appears more appealing than before, especially when combined with endocardial ablation(19). But again, current data specifies employing these techniques in highly selected cases.

Jerome FERRARA

and 10 more

Background: There is insufficient evidence regarding the comparison of Rapid Deployment aortic valve replacement(RDAVR) to TAVR in intermediate-risk patients with severe symptomatic aortic stenosis(AS) Aims: We compare the 2-years outcomes between RDAVR with INTUITY and TAVR with SAPIEN 3 in intermediate-risk patients with AS. Methods: Inclusion criteria: severe AS implanted with RDAVR or TAVR; EUROSCORE II ≥ 4% and clinical evaluation by Heart Team. Regression adjustment for the propensity score was used to compare RDAVR with TAVR(1:1). Primary endpoint: composite criterion of death, disabling stroke or rehospitalization. Secondary endpoints: occurrence of major bleeding post-operative complications, paravalvular regurgitation (PVR)≥2 and patient-prosthesis mismatch(PPM) at 1 month and pacemaker implantation at 2 years. Results: A total of 152 patients were included from 2012 to 2018: 48 in the RDAVR group and 104 in the TAVR group. Mean age was 82.7±6, 51.3% were female, mean Euroscore II was 6.03±1.6% and mean baseline LVEF was 56±13%,mean indexed iEOA was 0.41±0.1cm/m2, mean gradient was 51.7±14.7mmHg. Patients with RDAVR were younger(79.5±6vs82.6±6,p=0.01), at higher risk (EUROSCORE2 6,61±1,8%vs5,63±1,5%, p=0.005), combined surgery was performed in 28 patients(58.3%). Twenty-two patients(45.99%) met the primary outcome in the RDAVR group and 32 patients(66.67%) in the TAVR group. By 1:1propensity score matching analysis, there was a significant difference between both groups in favor of RDAVR(HR=0.58[95%CI:0.34;1.00],p=0.04). No difference were observed in PPM occurrence(0.83;[0.35-1.94];p=0.67),major bleeding events(1.33;[0.47-3.93];p=0.59),PVR≥2(0.33[0-6.28],p=0.46), and pacemaker implantation (0.84[0.25-2.84],p=0.77).Conclusion: RDAVR is associated with better 2-years outcomes than TAVR in intermediate-risk patients with severe symptomatic AS.

Francesca Mori

and 10 more

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