The point on the treatment of arrhythmic storm.

Arrhythmic storm is a clinical emergency associated with high mortality, which requires multi-disciplinary management. Reprogramming of the implantable cardiac defibrillator (ICD) aimed at reducing shocks, adrenergic blockade using beta-blockers, sedation/anxiolysis, and blockade of the stellate ganglion represent the first simple and effective manoeuvres, but further suppression of arrhythmias with antiarrhythmics is often required. A low-risk patient (e.g. monomorphic ventricular tachycardia, functioning ICD, and haemodynamically stable) should be managed with a beta-blocker (possibly non-selective) plus amiodarone, in addition to sedation with a benzodiazepine or dexmedetomidine; in patients at greater risk (high burden and haemodynamic instability), autonomic modulation with blockade of the stellate ganglion and the addition of a second antiarrhythmic (lidocaine) should be considered. In patients refractory to these measures, with advanced heart failure, general anaesthesia with intubation and the establishment of a haemodynamic circulatory support should be considered. Ablation, performed early, appears to be superior in terms of mortality and reduction of future shocks compared with titration of antiarrhythmics.

Acute pediatric encephalitis: etiology, course, and outcome of a 12-year single-center immunocompetent cohort.

BACKGROUND: Encephalitis is an uncommon but severe disorder due to an inflammation of the brain parenchyma, usually diagnosed on clinical, laboratory, electroencephalographic, and neuroradiological features. New causes of encephalitis have been reported in recent years, so diagnostic criteria have changed over time. We report on a single-center experience of a pediatric Hospital, the hub of its region, over 12 years (2008-2021), with the evaluation of all children managed for acute encephalitis. METHODS: We retrospectively reviewed clinical, laboratory, neuroradiological, and EEG data from the acute phase and outcome of all immunocompetent patients diagnosed with acute encephalitis. According to the newly proposed criteria for pediatric autoimmune encephalitis, we divided patients into infectious, definite autoimmune, probable autoimmune, and possible autoimmune, and performed a comparison between the different groups. RESULTS: 48 patients (26 females, mean age 4.4 years), 19 with infections, and 29 with autoimmune encephalitis, were included. Herpes simplex virus 1 encephalitis was the most frequently identified etiology followed by anti-NMDA receptor encephalitis. Movement disorders at onset and a longer hospital stay were observed more frequently in autoimmune compared to infectious encephalitis (p p < 0.001 and p = 0.001, respectively). Among the autoimmune group, children who started immunomodulatory treatment earlier (within 7 days from onset) had more frequent complete functional recovery (p = 0.002). CONCLUSIONS: Herpes virus and anti-NMDAR encephalitis are the most frequent etiologies within our cohort. Clinical onset and course are extremely variable. Since early immunomodulatory treatment was associated with a better functional outcome, our data confirm that a timely diagnostic classification in definite, probable, or possible autoimmune encephalitis can help the clinician in a successful therapeutic approach.

Role of miRNAs shuttled by mesenchymal stem cell-derived small extracellular vesicles in modulating neuroinflammation.

Mesenchymal stromal/stem cells (MSCs) are characterized by neuroprotective, immunomodulatory, and neuroregenerative properties, which support their therapeutic potential for inflammatory/neurodegenerative diseases, including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). One mode of action through which MSCs exert their immunomodulatory effects is release of extracellular vesicles that carry proteins, mRNAs, and microRNAs (miRNAs), which, once transferred, modify the function of target cells. We identified nine miRNAs significantly dysregulated in IFN-γ-primed MSCs, but present at different levels in their derived small extracellular vesicles (s-EV). We show that miR-467f and miR-466q modulate the pro-inflammatory phenotype of activated N9 microglia cells and of primary microglia acutely isolated from late symptomatic SOD1G93A mice, a murine ALS model, by downregulating Tnf and Il1b expression. Further analysis of the mode of action of miR-467f and miR-466q indicated that they dampen the pro-inflammatory phenotype of microglia by modulating p38 MAPK signaling pathway via inhibition of expression of their target genes, Map3k8 and Mk2. Finally, we demonstrated that in vivo administration of s-EV leads to decreased expression of neuroinflammation markers in the spinal cord of EAE-affected mice, albeit without affecting disease course. Overall, our data suggest that MSC-derived exosomes could affect neuroinflammation possibly through specific immunomodulatory miRNAs acting on microglia.

Challenging Cases of Wide Complex Tachycardias: Use and Limits of Algorithms.

Electrocardiographic algorithms are particularly useful to differentiate, in the presence of a wide complex tachycardia, between supraventricular aberrancy and ventricular tachycardias (VT). There are numerous limitations to the sensitivity and specificity of these algorithms including the presence of accessory pathways, use of antiarrhythmic drugs, congenital heart diseases, electrolytes impairments, and artificial pacing. Once the diagnosis of VT has been reached, other algorithms can help in localizing the origin of the ventricular arrhythmia. These approaches are also limited by the anatomic structure of where the arrhythmia originates. This article illustrates the difficulties in applying common algorithms in many clinical circumstances.

A Comparison of 3 Established Skeletal Age Estimation Methods in an African Group From Benin and an Italian Group From Southern Italy.

Age estimation is a crucial matter in several forensic and legal instances. The literature recommends carrying out hand and wrist radiograph to assess skeletal age. Much research has been conducted to examine the application of various methods in different categories. Our study aims to evaluate the reliability of Greulich and Pyle, Tanner-Whitehouse 2, and FELS methods in Beninese and Italian samples, with a total of 204 subjects, 102 (51 were male and 51 were female) from Benin and 102 (51 were male and 51 were female) from Italy, aged between 4 and 19 years. Hand-wrist radiographs were carried out at Saint Luc Hospital in Cotonou for the African sample and in 2 hospitals in Southern Italy for Italian sample. Skeletal maturity was obtained, applying the 3 methodologies. The arithmetic mean of the 3 ages obtained was calculated, as well as the possible difference between the known chronological age and the estimated mean skeletal age. Data were analyzed statistically using the χ test, Student t test, and Bland-Altman plots. There are no significant statistical differences between real age and skeletal age calculated using the Greulich and Pyle and FELS methods. Comparison between Tanner-Whitehouse 2 and the average of the methods used results in statistically significant, but clinically insignificant, differences.

Validity Comparison of Three Dental Methods for Age Estimation Based on Tooth Root Translucency.

Age estimation of nonliving subjects plays a very important role in identifying human remains. When adult remains are in question, this process becomes even more complex. Among the numerous dental methods that exist for adults aging, the evaluation of root translucency is one of the most useful. This study studies the correlation between age and root translucency by investigating monoradicular teeth affected by pathological processes using the equations proposed by Lamendin, Prince & Ubelaker and from Singhal et al. The average age values calculated according to the three methods were compared with the values of known age. Age estimation using the Student's t-test resulted as more accurate in the methods by Singhal et al. and by Prince & Ubelaker, with respect to that of Lamendin. Age estimation based solely on the percentage of radicular dentinal translucency has been found to be more accurate when diseased teeth are involved.

Not just right experience: is it influenced by feelings of guilt?

Individuals with obsessive-compulsive disorder (OCD) experience increased guilt. Further, these individuals often report uncomfortable sensations of things being not quite right ("not just right experiences"--NJREs). As to the relation between these psychological phenomena, it was hypothesized that feelings of guilt may enhance NJRE. In two experiments, we demonstrated that the induction of a guilty emotion resulted in increased NJRE, and this finding was qualified by an interaction with trait guilt. Induced guilt was followed by stronger feelings of things being not just right only in high-trait-guilt participants. In the low-trait-guilt participants NJRE was weaker. Moreover, we found a meaningful relationship between both NJRE and trait guilt and OCD features.

Immunological prevention of a multigene cancer syndrome.

Vaccines effectively prevent the onset of tumors in transgenic mice carrying activated oncogenes; however, human tumors are caused by combined alterations in oncogenes and oncosuppressor genes. We evaluated the impact of prophylactic vaccines in HER-2/neu transgenic, p53 wild-type/null mice that succumb to an aggressive cancer syndrome comprising mammary and salivary gland carcinomas and rhabdomyosarcoma. A vaccine made of allogeneic mammary carcinoma cells expressing HER-2/neu and interleukin 12 afforded long-term protection from tumor onset. Tumor prevention was mediated by T cell-derived cytokines, in particular gamma-interferon, and by anti-HER-2/neu antibodies. HER-2/neu expression was inhibited in target tissues of vaccinated mice, and somatic loss of the wild-type p53 allele did not occur. A highly effective vaccine against a single oncoprotein induced a powerful immune response that arrested multistep carcinogenesis in distinct target tissues.