Comparative safety and efficacy of paracetamol versus non-steroidal anti-inflammatory agents in neonates with patent ductus arteriosus: A systematic review and meta-analysis of randomized controlled trials.

AIM: Ibuprofen and indomethacin are the preferred drug treatment for patent ductus arteriosus (PDA) in preterm neonates. The comparative safety and efficacy of paracetamol as an alternative has not yet been well established. The aim of our study was to define the comparative efficacy and safety of paracetamol versus ibuprofen and indomethacin for PDA. METHODS: We performed a systematic literature search in PubMed, Scopus and Cochrane databases on randomized controlled trials comparing the efficacy and/or the safety of paracetamol versus ibuprofen and/or indomethacin and meta-analysed the available data. RESULTS: There were 1718 neonates from 20 eligible studies. Paracetamol did not differ from ibuprofen or indomethacin regarding the primary (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.69-1.26, P-value: 0.650, when compared to ibuprofen, and OR: 0.78; 95% CI: 0.20-3.02, P-value: 0.716, when compared to indomethacin) and overall (OR: 1.17; 95% CI: 0.82-1.66, P-value: 0.394, when compared to ibuprofen, and OR: 1.12; 95% CI: 0.58-2.15, P-value: 0.733, when compared to indomethacin) PDA closure rates. Paracetamol resulted in significantly reduced risk of oliguria and a tendency towards less gastrointestinal bleeding. CONCLUSION: There was no significant difference between paracetamol and ibuprofen or indomethacin in the PDA closure rates. However, paracetamol caused fewer adverse effects.

A systematic review and meta-analysis of interventional studies of bisphosphonates and denosumab in multiple myeloma and future perspectives.

Bisphosphonates (BPs) and denosumab (DENOS), due to their ability to inhibit osteoclast activity, are used to prevent skeletal complications in multiple myeloma (MM) patients. The NCBI PubMed, Web of Science, Scopus and ClinicalTrials.gov databases, were systematically searched for interventional studies, assessing the use of BP and DENOS in MM patients. Overall survival, disease progression, skeletal-related events, bone pain, osteonecrosis of the jaw (ONJ) and renal toxicity were the outcomes of interest. A total of 993 studies were retrieved and 43 were used for qualitative synthesis. Clodronate (CLOD) and zoledronic acid (ZOL) were effective in reducing skeletal complications compared to placebo. Results are mixed regarding the efficacy of pamidronate in reducing skeletal related events. ONJ rates were higher for ZOL, but under 5%, with CLOD having the safest profile. DENOS demonstrated non-inferiority to ZOL, in improving overall survival [pooled Hazard Ratio(HR) 1.02(95% CI 0.72,1.44)], progression free survival [pooled HR 0.92(95% CI 0.76,1.11)] and in reducing skeletal related events [pooled HR 1.03(95% CI 0.92,1.16)], with similar rates of ONJ and better safety profile regarding renal toxicity. Denosumab has comparable efficacy and safety with ZOL and may even replace BPs in the future, in the management of myeloma bone disease.

Investigation of routes of entry and dispersal pattern of RGNNV in tissues of European sea bass, Dicentrarchus labrax.

Viral encephalopathy and retinopathy (VER) is a serious neuropathological fish disease affecting in the Mediterranean aquaculture mainly European sea bass, Dicentrarchus labrax. It is well known that betanodaviruses are neurotropic viruses that replicate in nerve tissues, preferentially brain and retina. However, routes of entry and progression of the virus in the central nervous system (CNS) remain unclear. The role of four tissues-eye, oesophagus, gills and skin-as possible gateways of a betanodavirus, the redspotted grouper nervous necrosis virus (RGNNV), was investigated after experimental challenges performed on European seabass juveniles. The dispersal pattern of Betanodavirus at primarily stages of the disease was also assessed, using a real-time qPCR assay. The development of typical clinical signs of VER, the presence of characteristic histopathological lesions in the brain and retina and the detection of viral RNA in the tissues of all experimental groups ascertained that successful invasion of RGNNV under all experimental routes was achieved. Transneuronal spread along pathways known to be connected to the initial site of entry seems to be the predominant scenario of viral progression in the CNS. Furthermore, viraemia appeared only after the installation of the infection in the brain.

Fluoxetine vs. placebo for the treatment of recurrent vasovagal syncope with anxiety sensitivity.

AIMS: The optimal medical therapy of patients with vasovagal syncope (VVS) remains controversial. Fluoxetine is effective against anxiety and panic disorders, while its use has shown promising results for VVS. Anxiety sensitivity is a personality trait observed in a considerable proportion of patients with VVS, associated with predisposition to anxiety and panic disorders. Our aim was to examine whether fluoxetine exerts beneficial effects regarding VVS prevention in the subset of patients with anxiety sensitivity. METHODS AND RESULTS: We assessed 106 patients with typical history of recurrent VVS, without other comorbidities, and a diagnostic, positive head-up tilt test. A psychiatric examination ruled out clinical psychiatric disease. Their psychological, stress-related profile was assessed by the Anxiety Sensitivity Index (ASI) questionnaire, a 16-item questionnaire, assessing fear of anxiety-related sensations, previously studied in VVS. Patients scoring positive for ASI (n = 60, 57% of the population) were randomized in a 2:1 fashion to receive either 10-40 mg fluoxetine daily (n = 40) or placebo (n = 20), and were followed-up for 1 year. A significant difference was observed between patients receiving fluoxetine and those with placebo, regarding the distribution of syncope-free time during the study (P < 0.05). A significant difference was also observed between the two groups regarding presyncopal events and the total number of patients who experienced syncope or presyncope during follow-up. CONCLUSION: Sensitivity to anxiety is a common personality trait in recurrent VVS. Fluoxetine is superior to placebo against syncope in these patients. This drug may be a first-line pharmacological treatment for this difficult-to-treat group.

Box Lesion Isolation of the Left Atrial Posterior Wall with Radiofrequency Ablation Restricted in Predetermined Lines for the Treatment of Persistent Atrial Fibrillation: The Prognostic Role of Acute Interventional Outcome and Trigger Identification.

The left atrial posterior wall (PW) is known to be a critical substrate for the initiation and perpetuation of atrial fibrillation (AF) and has been explored as a target for catheter ablation, particularly in persistent AF (PerAF). In this retrospective study, we investigate the clinical outcome of patients with PerAF who underwent PW isolation (PWI) restricted in predetermined lines in addition to pulmonary vein isolation (PVI). One hundred consecutive patients (64 ± 9.1 years, 66% male, 20% with previous PVI ablation) underwent PWI in a box lesion setting for PerAF lasting >3 months (34% long-standing PerAF). PW triggers were defined as either foci from the PW that repeatedly induced AF or as isolated AF or atrial tachycardia (AT) within the PW. After a mean follow-up period of 25.6 ± 6.7 months, 61% of the patients remained in sinus rhythm after the last procedure. In 79 patients, the PW was successfully isolated, while, in 21 patients, complete isolation was not possible due to failure in completion of the roof line (n = 16), the floor line (n = 7), or both (n = 2). Patients with incomplete isolation had similar AF/AT recurrence rates compared to those with complete PWI. In 12 patients, PW triggers were identified, and PWI in these patients was shown to have a significantly better prognosis in terms of sinus rhythm maintenance (P = .031). Failure of complete PWI does not predispose a patient to an inferior outcome nor is it responsible for iatrogenic ATs. The presence of AF triggers within the PW leads to a particularly favorable result after box lesion isolation.

A 59-Year-Old Woman with Familial Brugada Syndrome and the c.664C>T Variant of the Sodium Voltage-Gated Channel Alpha Subunit 5 (SCN5A) Gene, Accompanied by Congenital Absence of the Right Coronary Artery, Patent Foramen Ovale, and Ischemic Stroke.

BACKGROUND Brugada syndrome is a rare inherited channelopathy that can lead to sudden cardiac death. The discovery of new variants of variable penetrance along with the current guidance for cascade family screening can be expected to lead to an increase in identified asymptomatic carriers of potentially causative mutations of channelopathies. A single coronary artery is a rare congenital anomaly of the coronary anatomy. We present a rare case of a 59-year-old woman with a family history of Brugada syndrome with the c.664C>T variant of the SCN5A gene, congenital absence of the right coronary artery, and patent foramen ovale. CASE REPORT We present a case of a patient with a family history of Brugada syndrome who tested positive for the SCN5A variant. The patient had no previous history of syncope or aborted sudden cardiac death. The patient had no features suggestive of Brugada type I ECG. An electrophysiology study was offered but the patient declined. She also complained of angina, and work-up with computed tomography coronary angiography revealed a congenital absence of the right coronary artery with no significant stenosis of the single left coronary artery. In the followup period, she suffered a stroke and was diagnosed with patent foramen ovale (PFO). She has been referred for PFO closure. CONCLUSIONS A rare case is reported of familial Brugada syndrome with absence of the right coronary artery and patent foramen ovale, which may have combined to increase this patient's risk for ischemic stroke.

Intermittent Loss of Telemetry Data: Lessons From a Leadless Pacemaker.

We present the case of a 63-year-old female patient who presented to the pacemaker clinic for a scheduled interrogation of her leadless pacemaker. The device interrogation was suggestive of intermittent under-sensing with failure to pace. Connecting the electrocardiogram lead to the pacing system analyzer raised the suspicion of intermittent loss of telemetry data. (Level of Difficulty: Beginner.).

Coronovirus Disease-2019 (COVID-19) Pandemic and Cardiac Electrophysiology: Guidance Protocol From a UK Tertiary Cardiac Center.

Since December 2019, the coronovirus disease-2019 (COVID-19) pandemic has resulted in more than 2,160,000 positive cases and more than 145,000 deaths until April 18, 2020. The pressure to the health services worldwide has been unprecedented. The redeployment of staff and resources to treat more efficiently COVID-19 cases along with the need to reduce disease transmission has affected the field of electrophysiology among many others. Amendments to clinical pathways are obligatory in this perspective to continue to provide the necessary health services to the people who need them, although at the same time, infection control and prevention are not compromised by inadvertent disease transmission or unnecessary use of resources. We aim to provide a guide of the logistic aspects of electrophysiology procedures derived from our tertiary cardiac center during the current COVID-19 pandemic.

Caduceus: A Medical Symbol of Deception, or Is There More to That?

The serpent is the most popular representative symbol of medicine. The two main figures commonly used are the rod of Asclepius and the caduceus. Much controversy exists in the literature on whether the caduceus is a false symbol for medicine or not. The history of how these depictions came to be ambassadors of the medical science is elusive to many physicians. Scholars suggest that the origin of this false belief dates back to 1902, when the US Army Medical Corps first incorporated the caduceus as its symbol. This current essay is an attempt to discover and interpret how the snake came to be part of the rod of Asclepius and the caduceus, and constitute the symbol of medicine in our days. It is widely accepted that a doctor's obligation is not only in healing the ill, but the task that is bestowed upon him is more complex. Therefore, one should be considered more of a physician rather than simply a doctor.

Self-assessment of health status is associated with inflammatory activation and predicts long-term outcomes in chronic heart failure.

AIMS: Clinicians lack a generally accepted means for health status assessment in chronic heart failure (CHF). We investigated the correlation between health status and inflammation burden as well as its long-term prognostic value in CHF outpatients. METHODS AND RESULTS: Kansas City Cardiomyopathy Questionnaires (KCCQ) were completed by 137 CHF outpatients (aged 64+/-12 years, mean ejection fraction 27+/-7%). Inflammatory markers [interleukin (IL)-6, IL-10, TNF-alpha, soluble Fas, Fas ligand, ICAM-1, VCAM-1], plasma B-type natriuretic peptide (BNP), 6 min walk test (6MWT), Zung self-rating depression scale, and Beck Depression Inventory were also assessed. Patients were followed for major cardiovascular events (death or hospitalization for disease progression) for up to 250 days. Patients with worse KCCQ-summary (KCCQ-s<50) score had lower 6MWT (P<0.05), and higher BNP (P<0.05) and pro-inflammatory markers (P<0.05) than those with KCCQ-s>or=50. Worse health status was also associated with shorter event-free survival (115+/-12 days for KCCQ-s<50 vs. 214+/-15 days for KCCQ-s>or=50, P=0.0179). Separating patients according KCCQ-functional score (KCCQ-f, cut-off 50) showed similar results. In multivariate Cox regression analysis, only LVEF (HR=0.637, 95% CI 0.450-0.900, P=0.011) and KCCQ-f (HR=0.035, 95% CI 0.002-0.824, P=0.037) were independent predictors of event-free survival at 250 days. CONCLUSION: KCCQ-s reflects neurohormonal and inflammatory burden in CHF. Among studied questionnaires, only KCCQ-f is an independent predictor of long-term event-free survival in CHF.

Sphenopalatine ganglion block: an external gate to modulate cardiac autonomic tone and suppress premature ventricular beats?

BACKGROUND: Autonomic modulation is used for treating various cardiovascular diseases, such as cardiac arrhythmias. Sphenopalatine ganglion (SPG) block is an easy, non-invasive therapy for migraine with a potential cardiovascular impact that remains unclear. In this study, we sought to assess the effect of SPG block on cardiac autonomic tone, as expressed by heart rate variability (HRV), and on ventricular arrhythmogenesis. METHODS: Forty patients (14 male and 26 female) suffering from migraine were randomized by 1:1 to SPG block or placebo (controls) and HRV parameters were evaluated 1 hour before and hourly after the intervention. Twenty-four additional patients (11 men and 13 women) with premature ventricular contractions (PVCs) from the right ventricular outflow tract underwent the same randomization and the number of PVCs was assessed during 1 hour before and every hour after treatment. Values were summarized as median (1st-3rd quartile). RESULTS: During the first four hours after SPG block, an increase in mean RR [883 (IQR, 869-948) vs. 839 (IQR, 806-887) ms at baseline, P<0.01], SDNN [64 (IQR, 59-69) vs. 51 (IQR, 47-55) ms, P<0.01], SDANN [39 (IQR, 36-43) vs. 27 (IQR, 22-29) ms, P<0.01], ASDNN [51 (IQR, 47-53) vs. 40 (IQR, 37-44) ms, P<0.01], rMSSD [30 (IQR, 27-32) vs. 25 (IQR, 23-27) ms, P<0.01], VLF [26 (IQR, 24-29) vs. 23 (IQR, 22-25) ms2, P<0.01] and HF [14 (IQR, 11-16) vs. 11 (IQR, 9-12) ms2, P<0.01], along with a decrease in LF/HF ratio [1.7 (IQR, 1.4-1.9) vs. 2.0 (IQR, 1.7-2.5), P<0.01] was observed in patients with migraine. In patients with PVCs, the number of ectopic ventricular beats per hour was decreased for the first five hours following SPG block [360 (IQR, 264-850) from 956 (IQR, 545-1,412), P<0.001]. No such differences were observed in controls. CONCLUSIONS: SPG block is associated with a transient increase in those HRV parameters that mainly express parasympathetic activity. It is also followed by a significant decrease in ventricular arrhythmic burden. These findings imply an effect on cardiac autonomic tone with a potential favorable clinical impact on arrhythmogenesis.

Differential multivariable risk prediction of appropriate shock versus competing mortality - A prospective cohort study to estimate benefits from ICD therapy.

BACKGROUND AND OBJECTIVE: We prospectively investigated combinations of risk stratifiers including multiple EP diagnostics in a cohort study of ICD patients. METHODS: For 672 enrolled patients, we collected history, LVEF, EP study and T-wave alternans testing, 24-h Holter, NT-proBNP, and the eGFR. All-cause mortality and first appropriate ICD shock were predefined endpoints. RESULTS: The 635 patients included in the final analyses were 63 ±â€¯13 years old, 81% were male, LVEF averaged 40 ±â€¯14%, 20% were inducible at EP study, 63% had a primary prophylactic ICD. During follow-up over 4.3 ±â€¯1.5 years, 108 patients died (4.0% per year), and appropriate shock therapy occurred in n = 96 (3.9% per year). In multivariate regression, age (p < 0.001), LVEF (p < 0.001), NYHA functional class (p = 0.007), eGFR (p = 0.024), a history of atrial fibrillation (p = 0.011), and NT-pro-BNP (p = 0.002) were predictors of mortality. LVEF (p = 0.002), inducibility at EP study (p = 0.007), and secondary prophylaxis (p = 0.002) were identified as independent predictors of appropriate shocks. A high annualized risk of shocks of about 10% per year was prevalent in the upper quintile of the shock score. In contrast, a low annual risk of shocks (1.8% per year) was found in the lower two quintiles of the shock score. The lower two quintiles of the mortality score featured an annual mortality <0.6%. CONCLUSIONS: In a prospective ICD patient cohort, a very good approximation of mortality versus arrhythmic risk was possible using a multivariable diagnostic strategy. EP stimulation is the best test to assess risk of arrhythmias resulting in ICD shocks.

Data on differential multivariable risk prediction of appropriate shock vs. competing mortality.

This data article features supplementary figures and tables related to the article "Differential Multivariable risk prediction of appropriate shock vs. competing mortality - a prospective cohort study to estimate benefits from implantable cardioverter defibrillator therapy" (Bergau et al., 2018) [1]. The figures show the clinical study CONSORT graph (data that show the number of patients not-analyzable as well as a distribution of patients by outcomes) and the correlation scatter plot for risk scores of appropriate shock vs. mortality (data that show the calculated score values of the two scores plotted against each other). The tables show the results for the univariate Cox regressions for prediction of mortality and appropriate shock. For further information, please see Bergau et al. (2018) [1].

Prevalence of heterozygous familial hypercholesterolaemia and its impact on long-term prognosis in patients with very early ST-segment elevation myocardial infarction in the era of statins.

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is an important cause of early onset coronary artery disease. We assessed the prevalence of clinical heterozygous FH (HeFH) among patients with very early ST-segment elevation myocardial infarction (STEMI), its management and its impact on long-term prognosis in the era of widespread utilization of statins. METHODS: We recruited prospectively 320 consecutive patients who had survived their first STEMI ≤35 years of age. Using the Dutch Lipid Clinic Network algorithm patients having HeFH (possible, probable or definite) were identified. RESULTS: Sixty-five patients (20.3%) had definite/probable HeFH and 163 patients (50.9%) had possible FH. Two years after discharge among 51 patients with definite/probable HeFH and available lipid levels, 43 (84.3%) were taking statins of whom 10 (23.3%) were on high-intensity statin therapy but only 1 (2.3%) of the statin-treated patients had LDL cholesterol levels <1.8 mmol/L (70 mg/dL). After a median follow-up of 9.1 years, major adverse coronary events (MACE) occurred in 99 (38.8%) of 255 patients with available follow-up information. Definite/probable HeFH was associated with an excess risk for recurrence of MACE independently of statin use, continuation of smoking after the STEMI, hypertension, diabetes mellitus, and sex (hazard ratio = 1.615, 95% confidence interval, 1.038 to 2.512, p = 0.03). CONCLUSIONS: One out of five patients who develop STEMI ≤35 years of age has definite/probable HeFH and despite the use of statins there is a therapeutic gap and a high recurrence rate of cardiac events during long-term follow-up.

Acute effects of unilateral temporary stellate ganglion block on human atrial electrophysiological properties and atrial fibrillation inducibility.

BACKGROUND: In experimental models, stellate ganglion block (SGB) reduces the induction of atrial fibrillation (AF), while data in humans are limited. OBJECTIVE: The aim of this study was to assess the effect of unilateral SGB on atrial electrophysiological properties and AF induction in patients with paroxysmal AF. METHODS: Thirty-six patients with paroxysmal AF were randomized in a 2:1 order to temporary, transcutaneous, pharmaceutical SGB with lidocaine or placebo before pulmonary vein isolation. Lidocaine was 1:1 randomly infused to the right or left ganglion. Before and after randomization, atrial effective refractory period (ERP) of each atrium, difference between right and left atrial ERP, intra- and interatrial conduction time, AF inducibility, and AF duration were assessed. RESULTS: After SGB, right atrial ERP was prolonged from a median (1st-3rd quartile) of 240 (220-268) ms to 260 (240-300) ms (P < .01) and left atrial ERP from 235 (220-260) ms to 245 (240-280) ms (P < .01). AF was induced by atrial pacing in all 24 patients before SGB, but only in 13 patients (54%) after the intervention (P < .01). AF duration was shorter after SGB: 1.5 (0.0-5.8) minutes from 5.5 (3.0-12.0) minutes (P < .01). Intra- and interatrial conduction time was not significantly prolonged. No significant differences were observed between right and left SGB. No changes were observed in the placebo group. CONCLUSION: Unilateral temporary SGB prolonged atrial ERP, reduced AF inducibility, and decreased AF duration. An equivalent effect of right and left SGB on both atria was observed. These findings may have a clinical implication in the prevention of drug refractory and postsurgery AF and deserve further clinical investigation.