The Impact of a Neurocritical Care and Neuropalliative Collaboration on Intensive Care Unit Outcomes.

Background: Neurocritical care (NCC) and neuropalliative care (NPC) clinicians provide care in specialized intensive care units (ICU). There is a paucity of data regarding the impact of NCC and NPC collaboration in smaller, community-focused settings.

Objective: To determine the clinical impact of introducing a NCC/NPC collaborative model in a mixed ICU community-based teaching hospital.

Identification of a SCN5A founder mutation causing sudden death, Brugada syndrome, and conduction blocks in Southern Italy.

Background: The genetic architecture of Brugada syndrome (BrS) is emerging as an increasingly complex area of investigation. The identification of genetically homogeneous populations can provide mechanistic insights and improve genotype-phenotype correlation.

Objective: To characterize and define the clinical implications of a novel BrS founder mutation.

Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome.

Background: Long QT syndrome (LQTS) is a common inheritable arrhythmogenic disorder, often secondary to mutations in the KCNQ1, KCNH2, and SCN5A genes. The disease is characterized by a prolonged ventricular repolarization (QTc interval) that confers susceptibility to life-threatening arrhythmic events (LAEs).

Objectives: This study sought to create an evidence-based risk stratification scheme to personalize the quantification of the arrhythmic risk in patients with LQTS.

Hydroquinidine Prevents Life-Threatening Arrhythmic Events in Patients With Short QT Syndrome.

Background: Short QT syndrome (SQTS) is a rare and life-threatening arrhythmogenic syndrome characterized by abbreviated repolarization. Hydroquinidine (HQ) prolongs the QT interval in SQTS patients, although whether it reduces cardiac events is currently unknown.

Objectives: This study investigated whether long-term treatment with HQ reduces the occurrence of life-threatening arrhythmic events (LAE) (cardiac arrest or sudden cardiac death) in SQTS patients.

Arrhythmogenic Right Ventricular Cardiomyopathy: Clinical Course and Predictors of Arrhythmic Risk.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of sudden cardiac death, but its progression over time and predictors of arrhythmias are still being defined.

Objectives: This study sought to describe the clinical course of ARVC and occurrence of life-threatening arrhythmic events (LAE) and cardiovascular mortality; identify risk factors associated with increased LAE risk; and define the response to therapy.

Methods: We determined the clinical course of 301 consecutive patients with ARVC using the Kaplan-Meier method adjusted to avoid the bias of delayed entry.

Clinical Presentation and Outcome of Brugada Syndrome Diagnosed With the New 2013 Criteria.

Introduction: The 2013 HRS/EHRA/APHRS consensus statement recommends the use of V1 and V2 leads recorded in the second and third intercostal spaces (High-ICS) for diagnosis of Brugada syndrome (BrS) creating a new category of patients discovered only with modified leads. The clinical presentation and the arrhythmic risk in these patients are ill defined. This study was aimed at assessing the role of High-ICS in the analysis of BrS and the clinical profile of the patients diagnosed only when ECG leads are moved to upper intercostal spaces.

Gene-Specific Therapy With Mexiletine Reduces Arrhythmic Events in Patients With Long QT Syndrome Type 3.

Background: Long QT syndrome type 3 (LQT3) is a lethal disease caused by gain-of-function mutations in the SCN5A gene, coding for the alpha-subunit of the sodium channel NaV1.5. Mexiletine is used to block late sodium current and to shorten QT interval in LQT3 patients.

Unusual retrospective prenatal findings in a male newborn with Timothy syndrome type 1.

Timothy syndrome 1 (TS1) is a multisystem disorder characterized by severe QT prolongation and potentially lethal ventricular arrhythmias in the first years of life, plus other cardiac and extracardiac manifestations caused by mutation in the CACNA1C gene, a CaV1.2 L-type calcium channel. Here, we report retrospectively an unusual fetal presentation on a second patient with TS1 with fetal hydrops due to a congenital AV block and its postnatal diagnosis by a marked prolongation of the corrected QTc interval of 570 ms and a missense mutation, p.

Efficacy and safety of a six-hour continuous overlap method for converting intravenous to transdermal fentanyl in cancer pain.

Context: Managing cancer pain often requires opioid medications, such as fentanyl, which is frequently initiated parenterally, and then converted to transdermal form. Little evidence exists to guide this conversion.

Objectives: To observe the efficacy and safety of a six-hour continuous overlap method for converting intravenous fentanyl (IVF) to transdermal fentanyl (TF) in patients with cancer pain.

Novel insight into the natural history of short QT syndrome.

Objectives: This study intends to gain further insights into the natural history, the yield of familial and genetic screening, and the arrhythmogenic mechanisms in the largest cohort of short QT syndrome (SQTS) patients described so far.

Background: SQTS is a rare genetic disorder associated with life-threatening arrhythmias, and its natural history is incompletely ascertained.

Methods: Seventy-three SQTS patients (84% male; age, 26 ± 15 years; corrected QT interval, 329 ± 22 ms) were studied, and 62 were followed for 60 ± 41 months (median, 56 months).

CaMKII inhibition rectifies arrhythmic phenotype in a patient-specific model of catecholaminergic polymorphic ventricular tachycardia.

Induced pluripotent stem cells (iPSC) offer a unique opportunity for developmental studies, disease modeling and regenerative medicine approaches in humans. The aim of our study was to create an in vitro 'patient-specific cell-based system' that could facilitate the screening of new therapeutic molecules for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited form of fatal arrhythmia. Here, we report the development of a cardiac model of CPVT through the generation of iPSC from a CPVT patient carrying a heterozygous mutation in the cardiac ryanodine receptor gene (RyR2) and their subsequent differentiation into cardiomyocytes (CMs).

KSHV ORF67 encoded lytic protein localizes on the nuclear membrane and alters emerin distribution.

p29, a newly identified Kaposi's sarcoma-associated herpesvirus (KSHV) protein, is the product of ORF67, the positional homolog of the conserved herpesvirus protein UL34. Like its homologues in other herpesviruses, p29 is expressed early during viral lytic cycle, and is localized on the nuclear rim. Upon chemical induction of viral replication in primary effusion lymphoma cells, p29 interacts with p33, encoded by ORF69, the positional homolog of the conserved herpesvirus protein UL31, and both proteins colocalize on the nuclear membrane.

19q13 microdeletion syndrome: Further refining the critical region.

The 19q13 microdeletion syndrome is a recently identified disorder of which very few cases have been reported so far. Growth deficiency, microcephaly, ectodermal anomalies and intellectual disability are the major features reported in all the described cases. The critical region has been estimated to span 750 Kb.

Genetic Testing for Cardiac Arrhythmias: Ready for Prime Time?

Despite the heterogeneity of substrates and clinical expressivity, genetic testing has a direct impact on clinical practice: it allows a specific diagnosis, including silent carriers (ie, asymptomatic diagnosis) and, in select diseases, the identification of a mutation has major impact for risk stratification and treatment of patients. This article addresses the role of genetic testing for each of the most epidemiologically relevant inherited arrhythmogenic diseases, specifically long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy.