Microbiome composition and presence of cultivable commensal groups of Southern Tamanduas (Tamandua tetradactyla) varies with captive conditions.

Southern Tamanduas (Tamandua tetradactyla) belong to the specialized placental myrmecophages. There is not much information about their intestinal microbiome. Moreover, due to their food specialization, it is difficult to create an adequate diet under breeding conditions. Therefore, we used 16S rDNA amplicon sequencing to analyze the fecal microbiome of captive Southern Tamanduas from four locations in the Czech Republic and evaluated the impact of the incoming diet and facility conditions on microbiome composition. Together with the microbiome analysis, we also quantified and identified cultivable commensals. The anteater fecal microbiome was dominated by the phyla Bacillota and Bacteroidota, while Pseudomonadota, Spirochaetota, and Actinobacteriota were less abundant. At the taxonomic family level, Lachnospiraceae, Prevotellaceae, Bacteroidaceae, Oscillospiraceae, Erysipelotrichaceae, Spirochaetaceae, Ruminococcaceae, Leuconostocaceae, and Streptococcaceae were mainly represented in the fecal microbiome of animals from all locations. Interestingly, Lactobacillaceae dominated in the location with a zoo-made diet. These animals also had significantly lower diversity of gut microbiome in comparison with animals from other locations fed mainly with a complete commercial diet. Moreover, captive conditions of analyzed anteater included other factors such as the enrichment of the diet with insect-based products, probiotic interventions, the presence of other animals in the exposure, which can potentially affect the composition of the microbiome and cultivable microbes. In total, 63 bacterial species from beneficial commensal to opportunistic pathogen were isolated and identified using MALDI-TOF MS in the set of more than one thousand selected isolates. Half of the detected species were present in the fecal microbiota of most animals, the rest varied across animals and locations.

Enthesitis and Dactylitis Resolution with Risankizumab for Active Psoriatic Arthritis: Integrated Analysis of the Randomized KEEPsAKE 1 and 2 Trials.

INTRODUCTION: The presence (vs absence) of enthesitis/dactylitis is associated with greater psoriatic arthritis (PsA) activity and reduced health-related quality of life. Risankizumab, an interleukin 23 antagonist, demonstrated superior treatment efficacy over placebo in patients with PsA, including enthesitis/dactylitis. Herein, we report the efficacy of risankizumab on complete resolution of enthesitis and/or dactylitis and improvements in patient-reported outcomes in patients with PsA. METHODS: This integrated post hoc analysis of data from KEEPsAKE 1 and KEEPsAKE 2 included patients with baseline enthesitis (Leeds Enthesitis Index > 0) and/or dactylitis (Leeds Dactylitis Index > 0). Efficacy outcomes at weeks 24 and 52 included proportion of patients achieving enthesitis and/or dactylitis resolution and minimal clinically important differences (MCID) in pain, Health Assessment Questionnaire-Disability Index, and Functional Assessment of Chronic Illness Therapy-Fatigue. RESULTS: Of 1407 patients, approximately 63%, 28%, and 20% had baseline enthesitis, dactylitis, and both enthesitis/dactylitis, respectively. At week 24, higher response rates were observed for risankizumab vs placebo for resolution of enthesitis, dactylitis, and both enthesitis/dactylitis (differences of 13.9%, 16.9%, and 13.3%, respectively; p < 0.05). By week 52, risankizumab treatment resulted in complete resolution of enthesitis, dactylitis, and both enthesitis and dactylitis in 55.0%, 76.1%, and 52.3% of patients; similar resolution rates occurred among patients who switched from placebo to risankizumab. Among risankizumab-treated patients who achieved resolution of enthesitis and/or dactylitis, MCIDs were also attained in patient-reported pain, disability, and fatigue at week 24 (all p < 0.05; except fatigue in patients with resolution of both enthesitis/dactylitis); responses were sustained through week 52. CONCLUSIONS: Higher proportions of risankizumab-treated (vs placebo-treated) patients achieved enthesitis and/or dactylitis resolution and meaningful improvements in patient-reported outcomes at week 24 and generally sustained responses at week 52. Thus, risankizumab may result in sustained alleviation of PsA-related pathognomonic musculoskeletal lesions of enthesitis/dactylitis. GOV IDENTIFIERS: NCT03675308, and NCT03671148.

Endomyocardial biopsy: safety and prognostic utility in paediatric and adult myocarditis in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry.

BACKGROUND AND AIMS: Contemporary multicentre data on clinical and diagnostic spectrum and outcome in myocarditis are limited. Study aims were to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. METHODS: Five hundred eighty-one (68.0% male) patients, 493 adults, median age 38 (27-52) years, and 88 children, aged 8 (3-13) years, were divided into 3 groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance; Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no cardiac magnetic resonance. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes. RESULTS: Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on cardiac magnetic resonance was found in 31.3% of children and in 57.9% of adults with biopsy-proven myocarditis (P < .001). At 1-year follow-up, 11/410 patients (2.7%) died, 7 (1.7%) received a heart transplant, 3 underwent VAD (0.7%), and 16 (3.9%) underwent ICD implantation. Independent predictors at diagnosis of death or heart transplantation or hospitalization or VAD implantation or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non-aetiology-driven therapy. CONCLUSIONS: Endomyocardial biopsy was safe, and cardiac magnetic resonance using Lake Louise criteria was less sensitive, particularly in children. Virus-negative lymphocytic myocarditis was predominant both in children and adults, and use of immunosuppressive treatments was low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis were independent predictors of unfavourable outcome events at 1 year.

Exploring the Clinical Presentation, Course, and Burden of Disease in Generalized Pustular Psoriasis [Podcast].

Generalized pustular psoriasis (GPP) is the most severe form of pustular psoriasis and affects large areas of the body. GPP is a rare disease, and has a variable presentation; thus, its diagnosis is challenging. The onset of symptoms is rapid, with the appearance of painful skin erythema, followed by the widespread eruption of sterile pustules. Acute GPP (called a flare) is often accompanied by systemic symptoms, including high fever, pain in skin lesions, malaise, and fatigue. Approximately half of GPP flares require hospitalization, with an average inpatient duration of 10-14 days. GPP prevalence estimates range from approximately 2-124 cases per million persons, with a female predominance. The most common age of onset of GPP is 40-60 years, although cases have been described in younger adults and children. GPP affects every aspect of patients' lives and has a high physical and psycho-social impact. Recent research on the interleukin-36 pathway associated with GPP led to the development of a GPP-specific treatment, spesolimab, which was approved by the US FDA in September 2022. This podcast explores the clinical presentation, disease course, and burden of disease in GPP, including differential diagnosis and common triggers of an acute flare.

Catheter Ablation for Ventricular Tachycardia in Patients With Desmoplakin Cardiomyopathy.

BACKGROUND: Desmoplakin (DSP) pathogenic/likely pathogenic (P/LP) variants are associated with malignant phenotypes of arrhythmogenic cardiomyopathy (DSP-ACM). Reports of outcomes after ventricular tachycardia (VT) ablation in DSP-ACM are scarce. OBJECTIVES: In this study, the authors sought to report on long-term outcomes of VT ablation in DSP-ACM. METHODS: Patients with P/LP DSP variants at 9 institutions undergoing VT ablation were included. Demographic, clinical, and instrumental data as well as all ventricular arrhythmia (VA) events were collected. Sustained VAs after the index procedure were the primary outcome. A per-patient before and after ablation comparison of rates of VA episodes per year was performed as well. RESULTS: Twenty-four DSP-ACM patients (39.3 ± 12.1 years of age, 62.5% male, median 6,116 [Q1-Q3: 3,362-7,760] premature ventricular complexes [PVCs] per 24 hours, median 4 [Q1-Q3: 2-11] previous VA episodes per patient at ablation) were included. Index procedure was most commonly endocardial/epicardial (19/24) The endocardium of the right ventricle (RV), the left ventricle (LV), or both ventricles were mapped in 8 (33.3%), 9 (37.5%), and 7 (29.2%) cases, respectively. Low voltage potentials were found in 10 of 15 patients in the RV and 11 of 16 in the LV. Endocardial ablation was performed in 18 patients (75.0%). Epicardial mapping in 19 patients (79.2%) identified low voltage potentials in 17, and 16 received epicardial ablation. Over the following 2.9 years (Q1-Q3: 1.8-5.5 years), 13 patients (54.2%) experienced VA recurrences. A significant reduction in per-patient event/year before and after ablation was observed (1.4 [Q1-Q3: 0.5-2.4] to 0.1 [Q1-Q3: 0.0-0.4]; P = 0.009). Two patients needed heart transplantation, and 4 died (3 of heart failure and 1 noncardiac death). CONCLUSIONS: VT ablation in DSP-ACM is effective in reducing the VA burden of the disease, but recurrences are common. Most VT circuits are epicardial, with both LV and RV low voltage abnormalities. Heart failure complicates clinical course and is an important cause of mortality.

Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study.

BACKGROUND: MYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene. OBJECTIVES: This study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies. METHODS: In this multicenter cohort study, penetrance and major cardiomyopathy-related events (MCEs) were assessed in carriers of (likely) pathogenic MYH7 variants by using Kaplan-Meier curves and log-rank tests. Prognostic factors were evaluated using Cox regression with time-dependent coefficients. RESULTS: In total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [IQR: 19.5-50.2 years]) were included. HCM was diagnosed in 226 subjects, NCCM in 70, and DCM in 55. Early penetrance and MCEs (age <12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted HR: 1.87; 95% CI: 1.15-3.04; P = 0.012) and at age ≤1 year in NCCM-associated or DCM-associated variant carriers (adjusted HR: 21.17; 95% CI: 4.81-93.20; P < 0.001) and subjects with a family history of early MCEs (adjusted HR: 2.45; 95% CI: 1.09-5.50; P = 0.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR: 1.82; 95% CI: 1.15-2.87; P = 0.010) and at age ≤5 years in NCCM-associated or DCM-associated variant carriers (adjusted HR: 38.82; 95% CI: 5.16-291.88; P < 0.001). CONCLUSIONS: MYH7 variants can cause cardiomyopathies and MCEs at a young age. Screening at younger ages may be warranted, particularly in carriers of NCCM- or DCM-associated variants and/or with a family history of MCEs at <12 years.

Safety of sodium-glucose cotransporter 2 inhibitors drugs among heart failure patients: a systematic review and meta-analysis.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) reduce morbidity and mortality for heart failure (HF) patients and are recommended as cornerstones for their medical therapy. Utilization in clinical practice remains low for multiple reasons, one of which may be adverse events. We investigated the incidence of these events to see if they are associated with SGLT2i use. A systematic search was performed in databases, including PubMed, Embase, Cochrane Library, Clinicaltrials.gov, and WHO's International Clinical Trials Registry Platform. Relevant randomized controlled trial studies assessing the safety outcomes of SGLT2i in HF patients were included in this study. We conducted the common-effect meta-analysis to estimate the relative risk (RR) and 95% confidence interval (CI) of safety outcomes in SGLT2i compared with placebo. Eighteen studies were included in the meta-analysis composed of 12 925 HF patients taking an SGLT2i and 12 747 taking a placebo. The meta-analysis indicated that the all-cause mortality and serious adverse events (SAEs) were lower in the SGLT2i group (RR, 0.91; 95% CI, 0.85-0.97; P = 0.005, I2 = 0%; and RR, 0.92; 95% CI, 0.90-0.95; P < 0.001, I2 = 43%, respectively). Volume depletion and genitourinary infections were more prevalent in the SGLT2i group (RR, 1.17; 95% CI, 1.06-1.28; P = 0.001, I2 = 0%; and RR, 1.27; 95% CI, 1.13-1.43; P < 0.001, I2 = 17%, respectively). Our meta-analysis demonstrated that using SGLT2is in HF patients was correlated with reduced mortality and SAEs, with a more prominent effect in HF with reduced ejection fraction patients and those taking dapagliflozin.

Are disease-specific patient-reported outcomes measures (PROMs) used in cardiogenetics? A systematic review.

Patient-reported outcome measures (PROMs) are used to facilitate patient-centered care (PCC). While studies in patients with cardiac conditions have revealed poorer health-related quality of life (HRQoL) and elevated emotional stress, studies in inherited cardiac conditions (ICC) seem rare. A systematic review evaluated which (specific domains of) PROMs are used in patients with ICC. From three databases (PubMed, PsychINFO, and Web of Science) quantitative studies investigating PROMs in patients with ICC were included. A Cochrane-based assessment tool was used to evaluate quality and potential risk of bias per subdomain. Data from 17 eligible articles were extracted. Among the included studies, risk of bias was predominantly high (35%) or unclear (30%). Most (n = 14) studies used a generic health status measure (SF-36, SF-12); 3 studies used a disease-specific PROM (KCCQ- cardiomyopathy and MLFHQ-heart failure). In addition to HRQoL measures, several studies used affective psychological measures (i.e., HADS, CAQ-18, IES-R, and IPQ). The mental health component of the PROMs showed lower scores overall in patients with ICC compared to population norms. Nine studies using HADS and GAD-7/PHQ-9 showed a prevalence of clinically significant anxiety (17-47%) and depression levels (8.3-28%) that were higher than the population norm (8.3% and 6.3%, respectively). HRQoL in patients with ICC is primarily assessed with generic PROMs. Results further confirmed high psychological morbidity in this population. Generic PROMS measures evaluate overall health status, but lack sensitivity to ICC-specific factors like heredity-related concerns. We propose developing a PROM specific for ICC to optimize PCC.

Long-term safety and efficacy of risankizumab for the treatment of moderate-to-severe plaque psoriasis: Interim analysis of the LIMMitless open-label extension trial up to 5 years of follow-up.

BACKGROUND: Psoriasis is a chronic, inflammatory skin disease often requiring long-term therapy. OBJECTIVE: To evaluate the long-term safety and efficacy of risankizumab in patients with psoriasis. METHODS: LIMMitless is an ongoing phase 3, open-label extension study evaluating the long-term safety and efficacy of continuous risankizumab 150 mg every 12 weeks for adults with moderate-to-severe plaque psoriasis following multiple phase 2/3 base studies. This interim analysis assessed safety (ie, monitored treatment-emergent adverse events [TEAEs]) through 304 weeks. Efficacy assessments included determining the proportion of patients who achieved ≥90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90/100), static Physician's Global Assessment of clear/almost clear (sPGA 0/1), and Dermatology Life Quality Index of no effect on patient's life (DLQI 0/1) through 256 weeks. RESULTS: Among 897 patients randomized to risankizumab in the base studies, 706 were still ongoing at data cutoff. Rates of TEAEs, TEAEs leading to discontinuation, and TEAEs of safety interest were low. At week 256, 85.1%/52.3% of patients achieved PASI 90/100, respectively, 85.8% achieved sPGA 0/1, and 76.4% achieved DLQI 0/1. LIMITATIONS: Open-label study with no placebo or active-comparator group. CONCLUSIONS: Long-term continuous risankizumab treatment for up to 5 years was well tolerated and demonstrated high and durable efficacy.

Iran Quality of Care in Medicine Program (IQCAMP): Design and Outcomes.

BACKGROUND: Assessment of quality and cost of medical care has become a core health policy concern. We conducted a nationwide survey to assess these measures in Iran as a developing country. To present the protocol for the Iran Quality of Care in Medicine Program (IQCAMP) study, which estimates the quality, cost, and utilization of health services for seven diseases in Iran. METHODS: We selected eight provinces for this nationally representative short longitudinal survey. Interviewers from each province were trained comprehensively. The standard definition of seven high-burden conditions (acute myocardial infarction [MI], heart failure [HF], diabetes mellitus [DM], stroke, chronic obstructive pulmonary (COPD) disease, major depression, and end-stage renal disease [ESRD]) helped customize a protocol for disease identification. With a 3-month follow-up window, the participants answered pre-specified questions four times. The expert panels developed a questionnaire in four modules (demographics, health status, utilization, cost, and quality). The expert panel chose an inclusive set of quality indicators from the current literature for each condition. The design team specified the necessary elements in the survey to calculate the cost of care for each condition. The utilization assessment included various services, including hospital admissions, outpatient visits, and medication. RESULTS: Totally, 156 specialists and 78 trained nurses assisted with patient identification, recruitment, and interviewing. A total of 1666 patients participated in the study, and 1291 patients completed all four visits. CONCLUSION: The IQCAMP study was the first healthcare utilization, cost, and quality survey in Iran with a longitudinal data collection to represent the pattern, quantity, and quality of medical care provided for high-burden conditions.

Novelties in Brugada Syndrome: Complex Genetics, Risk Stratification, and Catheter Ablation.

Brugada syndrome (BrS) is an inherited arrhythmia syndrome with distinctive electrocardiographic abnormalities in the right precordial leads and predisposes to ventricular arrhythmias and sudden cardiac death in otherwise healthy patients. Its complex genetic architecture and pathophysiological mechanism are not yet completely understood, and risk stratification remains challenging, particularly in patients at intermediate risk of arrhythmic events. Further understanding of its complex genetic architecture may help improving future risk stratification, and advances in management may contribute to alternatives to implantable cardioverter-defibrillators. Here, the authors review the latest insights and developments in BrS.

Dielectrophoresis microbial characterization and isolation of Staphylococcus aureus based on optimum crossover frequency.

Characterization of antibiotic-resistant bacteria is a significant concern that persists for the rapid classification and analysis of the bacteria. A technology that utilizes the manipulation of antibiotic-resistant bacteria is key to solving the significant threat of these pathogenic bacteria by rapid characterization profile. Dielectrophoresis (DEP) can differentiate between antibiotic-resistant and susceptible bacteria based on their physical structure and polarization properties. In this work, the DEP response of two Gram-positive bacteria, namely, Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-susceptible S. aureus (MSSA), was investigated and simulated. The DEP characterization was experimentally observed on the bacteria influenced by oxacillin and vancomycin antibiotics. MSSA control without antibiotics has crossover frequencies ( f x 0 ${f_{x0}}$ ) from 6 to 8 MHz, whereas MRSA control is from 2 to 3 MHz. The f x 0 ${f_{x0}}$ changed when bacteria were exposed to the antibiotic. As for MSSA, the f x 0 ${f_{x0}}$ decreased to 3.35 MHz compared to f x 0 ${f_{x0}}$ MSSA control without antibiotics, MRSA, f x 0 ${f_{x0}}$ increased to 7 MHz when compared to MRSA control. The changes in the DEP response of MSSA and MRSA with and without antibiotics were theoretically proven using MyDEP and COMSOL simulation and experimentally based on the modification to the bacteria cell walls. Thus, the DEP response can be employed as a label-free detectable method to sense and differentiate between resistant and susceptible strains with different antibiotic profiles. The developed method can be implemented on a single platform to analyze and identify bacteria for rapid, scalable, and accurate characterization.

Effect of Biologics on the Need for Procedural Interventions, Systemic Medications, and Healthcare Utilization in Patients with Hidradenitis Suppurativa: Real-World Data from the UNITE Registry.

INTRODUCTION: Management of hidradenitis suppurativa (HS) often requires a combined medical/procedural approach. Biologics are frequently reserved for severe cases after irreversible tissue damage has occurred. We evaluated the association between consistent biologic use and the need for procedural interventions, systemic medications, and healthcare utilization. METHODS: UNITE, a 4-year, global, prospective, observational, HS disease registry, documented the natural history, diagnostic/treatment patterns, and clinical outcomes of HS. Patients aged 12 years or more, with active HS were enrolled between October 2013 and December 2015 and evaluated every 6 months for 48 months at 73 sites across 12 countries (data cutoff December 2019). Proportions of patients requiring different HS procedures, systemic medications, and healthcare utilization were assessed during the 6-month periods before, during, and after biologic initiation for 12 weeks or more (i.e., consistent use). RESULTS: There were 63 instances of initiation of consistent biologic use (adalimumab [81%], infliximab [16%], and ustekinumab [3%]) in 57 patients. Patients' mean age was 40 years, 58% were female, and 53%/47% had Hurley stage II/III disease, respectively. Fewer patients required surgical/procedural interventions and systemic medications for the 6-month period during/6-month period after biologic initiation versus the 6-month period before biologic initiation, including intralesional corticosteroid injections (22%/14% vs 24%), incision and drainage (I&D) by physician (10%/10% vs 17%), I&D by patient (10%/10% vs 14%), surgical excision (8%/10% vs 11%), deroofing (5%/2% vs 5%), systemic antibiotics (43%/41% vs 54%), and systemic immunosuppressants (10%/6% vs 13%). Fewer patients required hospital admission for HS (17%/13% vs 21%) or emergency department visits for HS (8%/8% vs 16%) during the 6-month periods in which consistent biologics use started and continued versus the 6-month period before consistent biologic use. CONCLUSION: Following initiation of consistent biologic use (12 weeks or more), fewer patients required acute procedural interventions, systemic medications, and healthcare utilization, supporting the importance of early biologic initiation.

Cardiovascular Toxicity Associated With Immune Checkpoint Inhibitor Therapy: A Comprehensive Review.

Immune checkpoint inhibitors (ICIs), a significant breakthrough treatment of cancer, exert their function through enhancing the immune system's ability to recognize and attack cancer cells. However, these revolutionary cancer treatments have been associated with a range of immune-related adverse effects, including cardiovascular toxicity. The most commonly reported cardiovascular toxicities associated with ICIs are myocarditis, pericarditis, arrhythmias, and vasculitis. These cardiovascular manifestations are often severe and can lead to life-threatening complications. Therefore, prompt identification and management of these toxicities is critical, and a multidisciplinary teamwork by cardiologists and oncologists are required to ensure optimal patient outcomes. In this review, we summarize the current knowledge on the mechanisms underlying ICI-associated cardiovascular toxicity, clinical presentations of these toxicities, potential risk factors, diagnosis, management, and surveillance strategies during ICI therapy. While ICIs have already transformed cancer treatment, further research is needed to better understand and manage their immune-related cardiovascular effects, and possibly, to identify biomarkers which can predict the occurrence of these cardiovascular complications.

Importance of exercise stress testing in evaluation of unexplained cardiac arrest survivor.

BACKGROUND: In sudden cardiac arrest survivors without an immediately identifiable cause, additional extensive yet individualised testing is required. METHODS: We describe 3 survivors of sudden cardiac arrest in whom exercise stress testing was not performed during the initial hospital admission. RESULTS: All 3 patients were incorrectly diagnosed with long QT syndrome based on temporary sudden cardiac arrest-related heart rate-corrected QT interval prolongation, and exercise stress testing was not performed during the initial work-up. When they were subjected to exercise stress testing during follow-up, a delayed diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT) was made. As a result, these patients were initially managed inappropriately, and their family members were initially not screened for CPVT. CONCLUSION: In sudden cardiac arrest survivors without an immediately identifiable cause, omission of exercise stress testing or erroneous interpretation of the results can lead to a delayed or missed diagnosis of CPVT, which may have considerable implications for survivors and their family.

Use, misuse, and pitfalls of the drug challenge test in the diagnosis of the Brugada syndrome.

The diagnosis of Brugada syndrome (BrS) requires the presence of a coved (Type 1) ST segment elevation in the right precordial leads of the electrocardiogram (ECG). The dynamic nature of the ECG is well known, and in patients with suspected BrS but non-diagnostic ECG at baseline, a sodium channel blocker test (SCBT) is routinely used to unmask BrS. There is little doubt, however, that in asymptomatic patients, a drug-induced Brugada pattern is associated with a much better prognosis compared to a spontaneous Type 1 ECG. The SCBT is also increasingly used to delineate the arrhythmogenic substrate during ablation studies. In the absence of a "gold standard" for the diagnosis of BrS, sensitivity and specificity of the SCBT remain elusive. By studying patient groups with different underlying diseases, it has become clear that the specificity of the test may not be optimal. This review aims to discuss the pitfalls of the SCBT and provides some directions in whom and when to perform the test. It is concluded that because of the debated specificity and the overall very low risk for future events in asymptomatic individuals, patients should be properly selected and counseled before SCBT is performed and that SCBT should not be performed in asymptomatic patients with a Type 2 Brugada pattern and no family history of BrS or sudden death.

Species and Strain Variability among Sarcina Isolates from Diverse Mammalian Hosts.

Sarcina spp. has been isolated from the gastrointestinal tracts of diverse mammalian hosts. Their presence is often associated with host health complications, as is evident from many previously published medical case reports. However, only a handful of studies have made proper identification. Most other identifications were solely based on typical Sarcina-like morphology without genotyping. Therefore, the aim of this work was culture detection and the taxonomic classification of Sarcina isolates originating from different mammalian hosts. Sarcina-like colonies were isolated and collected during cultivation analyses of animal fecal samples (n = 197) from primates, dogs, calves of domestic cattle, elephants, and rhinoceroses. The study was carried out on apparently healthy animals kept in zoos or by breeders in the Czech Republic and Slovakia. Selected isolates were identified and compared using 16S rRNA gene sequencing and multi-locus sequence analysis (MLSA; Iles, pheT, pyrG, rplB, rplC, and rpsC). The results indicate the taxonomic variability of Sarcina isolates. S. ventriculi appears to be a common gut microorganism in various captive primates. In contrast, a random occurrence was also recorded in dogs. However, dog isolate N13/4e could represent the next potential novel Sarcina taxonomic unit. Also, a potentially novel Sarcina species was found in elephants, with occurrences in all tested hosts. S. maxima isolates were detected rarely, only in rhinoceroses. Although Sarcina bacteria are often linked to lethal diseases, our results indicate that Sarcina spp. appear to be a common member of the gut microbiota and seem to be an opportunistic pathogen. Further characterization and pathogenic analyses are required.

Individualized Family Screening for Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: Clinical guidelines recommend regular screening for arrhythmogenic right ventricular cardiomyopathy (ARVC) to monitor at-risk relatives, resulting in a significant burden on clinical resources. Prioritizing relatives on their probability of developing definite ARVC may provide more efficient patient care. OBJECTIVES: The aim of this study was to determine the predictors and probability of ARVC development over time among at-risk relatives. METHODS: A total of 136 relatives (46% men, median age 25.5 years [IQR: 15.8-44.4 years]) from the Netherlands Arrhythmogenic Cardiomyopathy Registry without definite ARVC by 2010 task force criteria were included. Phenotype was ascertained using electrocardiography, Holter monitoring, and cardiac imaging. Subjects were divided into groups with "possible ARVC" (only genetic or familial predisposition) and "borderline ARVC" (1 minor task force criterion plus genetic or familial predisposition). Cox regression was performed to determine predictors and multistate modeling to assess the probability of ARVC development. Results were replicated in an unrelated Italian cohort (57% men, median age 37.0 years [IQR: 25.4-50.4 years]). RESULTS: At baseline, 93 subjects (68%) had possible ARVC, and 43 (32%) had borderline ARVC. Follow-up was available for 123 relatives (90%). After 8.1 years (IQR: 4.2-11.4 years), 41 (33%) had developed definite ARVC. Independent of baseline phenotype, symptomatic subjects (P = 0.014) and those 20 to 30 years of age (P = 0.002) had a higher hazard of developing definite ARVC. Furthermore, patients with borderline ARVC had a higher probability of developing definite ARVC compared with those with possible ARVC (1-year probability 13% vs 0.6%, 3-year probability 35% vs 5%; P < 0.01). External replication showed comparable results (P > 0.05). CONCLUSIONS: Symptomatic relatives, those 20 to 30 years of age, and those with borderline ARVC have a higher probability of developing definite ARVC. These patients may benefit from more frequent follow-up, while others may be monitored less often.