Right Bundle Branch Block Predicts Appropriate Implantable Cardioverter Defibrillator Therapies in Patients with Non-Ischemic Dilated Cardiomyopathy and a Prophylactic Implantable Cardioverter Defibrillator.

Background: The benefit of prophylactic implantable cardioverter defibrillators (ICDs) in patients with severe systolic dysfunction of non-ischemic origin is still unclear, and the identification of patients at risk for sudden cardiac death remains a major challenge. Aims/Methods: We retrospectively reviewed all consecutive patients with non-ischemic dilated cardiomyopathy (NICM) who underwent prophylactic ICD implantation between 2008 and 2020 in two tertiary centers. Our main goal was to identify the predictors of appropriate ICD therapies (anti-tachycardia pacing [ATP] and/or shocks) in this cohort of patients. Results: A total of 224 patients were included. After a median follow-up of 51 months, 61 patients (27.2%) required appropriate ICD therapies. Patients with appropriate ICD therapies were more frequently men (87% vs. 69%, p = 0.006), of younger age (59 years, (53-65) vs. 64 years, (57-70); p = 0.02), showed more right bundle branch blocks (RBBBs) (15% vs. 4%, p = 0.007) and less left bundle branch blocks (LBBBs) (26% vs. 47%, p = 0.005) in the ECG, and had higher left ventricular end-diastolic (100 mL/m2, (90-117) vs. 86, (71-110); p = 0.011) and systolic volumes (72 mL/m2, (59-87) vs. 61, (47-81), p = 0.05). In a multivariate competing-risks regression analysis, RBBB (HR 2.26, CI 95% 1.02-4.98, p = 0.043) was identified as an independent predictor of appropriate ICD therapies. Conclusion: RBBBs may help to identify patients with NICM at high risk of ventricular arrhythmias and requiring ICD intervention.

Remote Dielectric Sensing Before and After Discharge in Patients With ADHF: The ReDS-SAFE HF Trial.

BACKGROUND: Incomplete treatment of congestion often leads to worsening heart failure (HF). The remote dielectric sensing (ReDS) system is an electromagnetic energy-based technology that accurately quantifies changes in lung fluid concentration noninvasively. OBJECTIVES: This study sought to assess whether an ReDS-guided strategy during acutely decompensated HF hospitalization is superior to routine care for improving outcomes at 1 month postdischarge. METHODS: ReDS-SAFE HF (Use of ReDS for a SAFE discharge in patients with acute Heart Failure) was an investigator-initiated, multicenter, single-blind, randomized, proof-of-concept trial in which 100 patients were randomized to a routine care strategy, with discharge criteria based on current clinical practice, or an ReDS-guided decongestion strategy, with discharge criteria requiring an ReDS value of ≤35%. ReDS measurements were performed daily and at a 7-day follow-up visit, with patients and treating physicians in the routine care arm blinded to the results. The primary outcome was a composite of unplanned visits for HF, HF rehospitalization, or death at 1 month after discharge. RESULTS: The mean age was 67 ± 14 years, and 74% were male. On admission, left ventricular ejection fraction was 37% ± 16%, and B-type natriuretic peptide was 940 pg/L (Q1-Q3: 529-1,665 pg/L). The primary endpoint occurred in 10 (20%) patients in the routine care group and 1 (2%) in the ReDS-guided strategy group (log-rank P = 0.005). The ReDS-guided strategy group experienced a lower event rate, with an HR of 0.094 (95% CI: 0.012-0.731; P = 0.003), and a number of patients needed to treat of 6 to avoid an event (95% CI: 3-17), mainly resulting from a decrease in HF readmissions. The median length of stay was 2 days longer in the ReDS-guided group vs the routine care group (8 vs 6; P = 0.203). CONCLUSIONS: A ReDS-guided strategy to treat congestion improved 1-month prognosis postdischarge in this proof-of-concept study, mainly because of a decrease of the number of HF readmissions. (Use of ReDS for a SAFE discharge in patients with acute Heart Failure [ReDS-SAFE HF]; NCT04305717).

Human lifespan and sex-specific patterns of resilience to disease: a retrospective population-wide cohort study.

BACKGROUND: Slower paces of aging are related to lower risk of developing diseases and premature death. Therefore, the greatest challenge of modern societies is to ensure that the increase in lifespan is accompanied by an increase in health span. To better understand the differences in human lifespan, new insight concerning the relationship between lifespan and the age of onset of diseases, and the ability to avoid them is needed. We aimed to comprehensively study, at a population-wide level, the sex-specific disease patterns associated with human lifespan. METHODS: Observational data from the SIDIAP database of a cohort of 482,058 individuals that died in Catalonia (Spain) at ages over 50 years old between the 1st of January 2006 and the 30th of June 2022 were included. The time to the onset of the first disease in multiple organ systems, the prevalence of escapers, the percentage of life free of disease, and their relationship with lifespan were evaluated considering sex-specific traits. RESULTS: In the study cohort, 50.4% of the participants were women and the mean lifespan was 83 years. The results show novel relationships between the age of onset of disease, health span, and lifespan. The key findings include: Firstly, the onset of both single and multisystem diseases is progressively delayed as lifespan increases. Secondly, the prevalence of escapers is lower in lifespans around life expectancy. Thirdly, the number of disease-free systems decreases until individuals reach lifespans around 87-88 years old, at which point it starts to increase. Furthermore, long-lived women are less susceptible to multisystem diseases. The associations between health span and lifespan are system-dependent, and disease onset and the percentage of life spent free of disease at the time of death contribute to explaining lifespan variability. Lastly, the study highlights significant system-specific disparities between women and men. CONCLUSIONS: Health interventions focused on delaying aging and age-related diseases should be the most effective in increasing not only lifespan but also health span. The findings of this research highlight the relevance of Electronic Health Records in studying the aging process and open up new possibilities in age-related disease prevention that should assist primary care professionals in devising individualized care and treatment plans.

Impact of an Intervention to Promote the Vaccination of Patients with Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) have a dysregulated immune system, being at high risk of opportunistic infections. Low vaccination rates hinder the prevention of such diseases. Therefore, we implemented an intervention to increase vaccination rates, and we aimed to evaluate the effect. We determined the change in professionals and the change in the vaccination rates after the intervention. A quasi-experimental study was carried out using data from 31 December 2016 to 31 December 2021. First, healthcare professionals specializing in IBD agreed on a vaccination protocol; then, this protocol was passed on to the professionals involved in vaccination. We evaluated the perception of knowledge, capacity, and intention to vaccinate patients with IBD among the professionals before and after the intervention with a survey. We also described the effectiveness of the intervention for already diagnosed patients and compared the vaccination rates between patients diagnosed prior to the intervention and newly diagnosed patients. The intervention resulted in an improved perception of knowledge, capacity, and intention to vaccinate patients with IBD among the professionals (p < 0.05). Moreover, during the post-intervention period, in the 315 patients, the vaccination rate increased for all immune-preventable diseases (p < 0.05). The professionals positively valued the intervention, and compliance with the recommended vaccination protocol in patients with IBD improved significantly.

Real-life experience in two cases of secondary prophylaxis with letermovir for CMV infection in solid organ transplantation.

IMPORTANCE: This observation provides comprehensive data on the clinical correlates of both cytomegalovirus (CMV) genotypic follow-up and clinical monitoring and outcomes for two different solid organ transplantation recipients that received letermovir as secondary prophylaxis. Our study emphasizes that monitoring of CMV disease in the patient and early genotypic detection of resistance mutations are essential when using new antiviral drugs for off-label indication in patients experiencing CMV relapses or not responding to standard antiviral therapy. These cases and the bibliography reviewed can be helpful for other researchers and clinicians working in the field to optimize the use of new treatments for transplant recipients since drug-resistant CMV infection is an important emerging problem even with new developments in antiviral treatment.

Comparison of heart, grace and TIMI scores to predict major adverse cardiac events from chest pain in a Spanish health care region.

Acute non-traumatic chest pain (ANTCP) is the second cause of consultation in the Emergency department (ED). About 70% of all Acute Myocardial Infarctions present as non persistent ST-elevation acute coronary syndrome (NSTE-ACS) in the electrocardiogram. Our aim was to compare whether the HEART risk score is more effective than the GRACE and TIMI scores for the diagnosis and prognosis of Major Adverse Cardiac Events (MACE) at six weeks in patients with ANTCP and NSTE-ACS. A prospective cohort study was conducted with patients with ANTCP that attended an ED and a Primary Care Emergency Center (PCEC) from April 2018 to December 2020. The primary outcome was MACE at six weeks. Diagnostic performance was calculated for each scale as the Area under the Receiver Operating Characteristic (ROC) curve (AUC), sensitivity (SE), specificity (SP), and predictive values (PV). Qualitative variables were compared using the Chi-square test, and continuous variables were compared using the nonparametric Kruskal-Wallis test. We adjusted a logistic regression for risk groups, age, and gender to determine the effect of the HEART, GRACE, and TIMI scores on MACE. The degree of agreement (kappa index) was calculated in the categorical classification of patients according to the three risk scales. Cox proportional hazards regressions were performed for each scale and were compared using partial likelihood ratio tests for non-nested models. From a sample of 317 patients with ANTCP, 14.82% had MACE at six weeks. The AUC was 0.743 (95% CI 0.67-0.81) for the HEART score, 0.717 (95% CI 0.64-0.79) for the TIMI score, and 0.649 (95% CI 0.561-0.738) for the GRACE score. The HEART scale identified low-risk patients with a higher SE and negative PV than the GRACE and TIMI scores. The HEART scale was better than the GRACE and TIMI scores at diagnosing and predicting MACE at six weeks in patients with ANTCP and probable NSTE-ACS. It was also a reliable tool for risk stratification in low-risk patients. Its application is feasible in EDs and PCECs, avoiding the need for complementary tests and their associated costs without compromising patient health.

Assessment of Pain Treatments in Disorders of Upper Limbs: A Qualitative Study Protocol Based on Patients' Experiences.

Chronic musculoskeletal pain (CMP) is one of the most common symptoms of musculoskeletal disorders. Carpal tunnel syndrome (CTS) and subacromial syndrome (SAS) are the most prevalent musculoskeletal disorders of the upper limbs. By collecting the opinions of patients with CTS and SAS, we aim to identify variables that could be introduced in the follow-up of CMP, and to detect barriers and facilitators of its treatments to improve their acceptance. This qualitative study is being conducted in Lleida, Spain, and explores the experiences and feelings of patients, and their acceptance of the standard of care. It follows the consolidated criteria for reporting qualitative research (COREQ) through focus groups, addressing issues with rigor and representativeness. By collecting patients' opinions, we expect to obtain valuable information to complement the set of variables previously used by health professionals in the follow-up of CMP, and to understand treatment barriers and facilitators.

Effects of the COVID-19 Pandemic on the Decision and Doubts About Vaccination in Catalonia: Online Cross-sectional Questionnaire.

BACKGROUND: Hesitancy to get vaccinated during the COVID-19 pandemic may decrease vaccination coverage and facilitate the occurrence of local or global outbreaks. OBJECTIVE: The objective of this study was to analyze the impact of the COVID-19 pandemic in Catalonia on 3 aspects: the decision to get vaccinated against COVID-19, changes in opinion about vaccination in general, and the decision to get vaccinated against other diseases. METHODS: We performed an observational study with the population of Catalonia aged 18 years or over, obtaining information through a self-completed questionnaire in electronic format. Differences between groups were determined using the chi-square test, Mann-Whitney U test, or the Student t test. RESULTS: We analyzed the answers from 1188 respondents, of which 870 were women, 47.0% (558/1187) had sons or daughters under the age of 14 years, and 71.7% (852/1188) had studied at university. Regarding vaccination, 16.3% (193/1187) stated that they had refused a vaccine on some occasion, 76.3% (907/1188) totally agreed with vaccines, 1.9% (23/1188) were indifferent, and 3.5% (41/1188) and 1.2% (14/1188) slightly or totally disagreed with vaccination, respectively. As a result of the pandemic, 90.8% (1069/1177) stated that they would get vaccinated against COVID-19 when they are asked, while 9.2% (108/1177) stated the opposite. A greater intention to get vaccinated was observed among women; people older than 50 years; people without children under 15 years of age; people with beliefs, culture, or family in favor of vaccination; respondents who had not previously rejected other vaccines, were totally in favor of vaccines, or had not increased their doubts about vaccination; and respondents who had not changed their decision about vaccines as a result of the pandemic. Finally, 30.3% (359/1183) reported an increase in their doubts regarding vaccination, and 13.0% (154/1182) stated that they had changed their decision about routinely recommended vaccines as a result of the pandemic. CONCLUSIONS: The population studied was predominantly in favor of vaccination; however, the percentage of people specifically rejecting vaccination against COVID-19 was high. As a result of the pandemic, we detected an increase in doubts about vaccines. Although the final decision about vaccination did not primarily change, some of the respondents did change their opinion about routine vaccinations. This seed of doubt about vaccines may be worrisome as we aim to maintain high vaccination coverage.

Plasma acylcarnitines and gut-derived aromatic amino acids as sex-specific hub metabolites of the human aging metabolome.

Aging biology entails a cell/tissue deregulated metabolism that affects all levels of biological organization. Therefore, the application of "omic" techniques that are closer to phenotype, such as metabolomics, to the study of the aging process should be a turning point in the definition of cellular processes involved. The main objective of the present study was to describe the changes in plasma metabolome associated with biological aging and the role of sex in the metabolic regulation during aging. A high-throughput untargeted metabolomic analysis was applied in plasma samples to detect hub metabolites and biomarkers of aging incorporating a sex/gender perspective. A cohort of 1030 healthy human adults (45.9% females, and 54.1% males) from 50 to 98 years of age was used. Results were validated using two independent cohorts (1: n = 146, 53% females, 30-100 years old; 2: n = 68, 70% females, 19-107 years old). Metabolites related to lipid and aromatic amino acid (AAA) metabolisms arose as the main metabolic pathways affected by age, with a high influence of sex. Globally, we describe changes in bioenergetic pathways that point to a decrease in mitochondrial ß-oxidation and an accumulation of unsaturated fatty acids and acylcarnitines that could be responsible for the increment of oxidative damage and inflammation characteristic of this physiological process. Furthermore, we describe for the first time the importance of gut-derived AAA catabolites in the aging process describing novel biomarkers that could contribute to better understand this physiological process but also age-related diseases.

Screening oropharyngeal dysphagia in patients with head and neck cancer in a radiation oncology department.

Background: Oropharyngeal dysphagia (OD) occurs in up to 40% of head and neck cancer (HNC) patients before treatment and remains a common symptom (23-60%) after oncological treatments, leading to several consequences. Early detection is essential for effective swallowing-rehabilitation and nutritional-support. The increased radiosensitivity of tumors associated with human papillomavirus (HPV) and advances in imaging techniques have stimulated research into deintensified strategies to minimize radiotherapy (RT) side effects. The purposes of the study are to establish the percentage of patients with HNC who are candidates to RT who are at risk of dysphagia [Eating Assessment Tool (EAT) score ≥ 3], determine if tumor location and previous surgery were related to a higher risk of dysphagia and if patients suffering severe toxicity during cancer therapy are at greater risk of posttreatment-dysphagia. Materials and methods: Patients diagnosed of HNC who were referred to RT treatment at our Radiation Oncology Department were prospectively included. Questionnaire EAT-10 was filled in the first assessment used as a screening tool and repeated one month after treatment. Treatment toxicity was established according to common toxicity criteria adverse effects (CTCAE4.03). Results: From November 2019 to January 2021, 72 patients were included. All completed pretreatment EAT-10 questionnaire. The mean (SD) score of the pretreatment EAT-10 was 7.26 ± 11.19 and 43.1% were at dysphagia risk. Patients with tumors located in the oral cavity, oropharynx and those that had received surgery prior to RT had higher risk than the rest of locations or those who had not previous surgery (p = 0.001 and p = 0.002, respectively). After oncological treatment 95.83% completed EAT-10 post-treatment and 45,6% showed positive EAT-10 score. Conclusions: Patients with tumors in the oral cavity or oropharynx, presenting in advanced stage, and who previously received surgery are at higher risk of developing dysphagia. The EAT-10 is a simple tool that can help us identify those patients and refer them for an intensive evaluation to reduce dysphagia-consequences.

Genetic Study of SARS-CoV-2 Non Structural Protein 12 in COVID-19 Patients Non Responders to Remdesivir.

Remdesivir (RDV) was the first antiviral drug approved by the FDA to treat severe coronavirus disease-2019 (COVID-19) patients. RDV inhibits SARS-CoV-2 replication by stalling the non structural protein 12 (nsp12) subunit of the RNA-dependent RNA polymerase (RdRp). No evidence of global widespread RDV-resistance mutations has been reported, however, defining genetic pathways to RDV resistance and determining emergent mutations prior and subsequent antiviral therapy in clinical settings is necessary. This study identified 57/149 (38.3%) patients who did not respond to one course (5-days) (n = 36/111, 32.4%) or prolonged (5 to 20 days) (n = 21/38, 55.3%) RDV therapy by subgenomic RNA detection. Genetic variants in the nsp12 gene were detected in 29/49 (59.2%) non responder patients by Illumina sequencing, including the de novo E83D mutation that emerged in an immunosuppressed patient after receiving 10 + 8 days of RDV, and the L838I detected at baseline and/or after prolonged RDV treatment in 9/49 (18.4%) non responder subjects. Although 3D protein modeling predicted no interference with RDV, the amino acid substitutions detected in the nsp12 involved changes on the electrostatic outer surface and in secondary structures that may alter antiviral response. It is important for health surveillance to study potential mutations associated with drug resistance as well as the benefit of RDV retreatment, especially in immunosuppressed patients and in those with persistent replication. IMPORTANCE This study provides clinical and microbiologic data of an extended population of hospitalized patients for COVID-19 pneumonia who experienced treatment failure, detected by the presence of subgenomic RNA (sgRNA). The genetic variants found in the nsp12 pharmacological target of RDV bring into focus the importance of monitoring emergent mutations, one of the objectives of the World Health Organization (WHO) for health surveillance. These mutations become even more crucial as RDV keeps being prescribed and new molecules are being repurposed for the treatment of COVID-19. The present article offers new perspectives for the clinical management of non responder patients treated and retreated with RDV and emphasizes the need of further research of the benefit of combinatorial therapies and RDV retreatment, especially in immunosuppressed patients with persistent replication after therapy.

Role of sex on the efficacy of pharmacological and non-pharmacological treatment of heart failure with reduced ejection fraction: A systematic review.

Background: Heart Failure (HF) is a growing epidemic with a similar prevalence in men and women. However, women have historically been underrepresented in clinical trials, leading to uneven evidence regarding the benefit of guideline-directed medical therapy (GDMT). This review aims to outline the sex differences in the efficacy of pharmacological and non-pharmacological treatment of HF with reduced ejection fraction (HFrEF). Methods and results: We conducted a systematic review via Medline from inception to 31 January 2022, including all randomized clinical trials published in English including adult patients suffering HFrEF that reported data on the efficacy of each drug. Baseline clinical characteristics, primary outcomes, and sex-specific effects are summarized in tables. The systemic review has been conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. In total, 29 articles were included in the systematic review. We observed that the proportion of women enrolled in clinical trials was generally low, the absence of a prespecified analysis of efficacy by sex was frequent, and the level of quality of evidence on the efficacy of GDMT and implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT-) in women was relatively poor. Conclusions: Sex influences the response to treatment of patients suffering from HFrEF. All the results from the landmark randomized clinical trials are based on study populations composed mainly of men. Further studies specifically designed considering sex differences are warranted to elucidate if GDMT and new devices are equally effective in both sexes.

Genotypic and Phenotypic Study of Antiviral Resistance Mutations in Refractory Cytomegalovirus Infection.

BACKGROUND: This study describes the genotypic and phenotypic characterization of novel human cytomegalovirus (HCMV) genetic variants of a cohort of 94 clinically resistant HCMV patients. METHODS AND RESULTS: Antiviral-resistant mutations were detected in the UL97, UL54, and UL56 target genes of 25 of 94 (26.6%) patients. The genotype-phenotype correlation study resolved the status of 5 uncharacterized UL54 deoxyribonucleic acid polymerase (G441S, A543V, F460S, R512C, A928T) and 2 UL56 terminase (F345L, P800L) mutations found in clinical isolates. A928T conferred high, triple resistance to ganciclovir, foscarnet, and cidofovir, and A543V had 10-fold reduced susceptibility to cidofovir. Viral growth assays showed G441S, A543V, F345L, and P800L impaired viral growth capacities compared with wild-type AD169 HCMV. Three-dimensional modeling predicted A543V and A928T phenotypes but not R512C, reinforcing the need for individual characterization of mutations by recombinant phenotyping. CONCLUSIONS: Extending mutation databases is crucial to optimize treatments and to improve the assessment of patients with resistant/refractory HCMV infection.

Enhancing Night and Day Circadian Contrast through Sleep Education in Prediabetes and Type 2 Diabetes Mellitus: A Randomized Controlled Trial.

BACKGROUND: Evidence supports a causal relationship between circadian disturbance and impaired glucose homeostasis. METHODS: To determine the effect of an educational intervention delivered by primary care nurses to improve sleep hygiene, a parallel, open-label clinical trial in subjects aged 18 and older with impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM) was performed. Study variables were sex, age, fasting glucose, glycated haemoglobin A1c (HbA1c), Pittsburgh Sleep Quality Index (PSQI), sleep duration and efficiency, body mass index, antidiabetic treatment, diet and physical exercise. An individual informative educational intervention was carried out following a bidirectional feedback method. The intervention aimed to develop skills to improve sleep through nine simple tips. An analysis of covariance was performed on all the mean centred outcome variables controlling for the respective baseline scores. RESULTS: In the intervention group, PSQI dropped, the duration and quality of sleep increased, and a decrease in fasting glucose and in HbA1c levels was observed. CONCLUSION: The proposed intervention is effective for improving sleep quality, length and efficiency, and for decreasing fasting glucose and HbA1c levels in only 3 months. These findings support the importance of sleep and circadian rhythm education focused on improving IFG and T2DM.

Lack of Usefulness of Donor-Derived Cell-Free DNA as a Biomarker for Cardiac Allograft Vasculopathy: A Prospective Study.

Background: Cardiac allograft vasculopathy (CAV) remains a major cause of morbidity and mortality among long-term heart transplant recipients. There is an unmet need for a non-invasive biomarker of CAV that could obviate the need to perform surveillance coronary angiograms in these patients. Our aim was to evaluate the performance of Donor-derived Cell Free DNA (dd-cfDNA) as a biomarker of CAV. Methods: We prospectively measured dd-cfDNA levels in all patients undergoing routine coronary angiography >1 year after heart transplant at a single center. Endpoints included the association between dd-cfDNA levels and the presence CAV, according to several prespecified criteria. Results: We included 94 heart transplant recipients, a median of 10.9 years after transplant. Coronary angiogram revealed CAV0, CAV1, CAV2, and CAV3 in 61, 19, 14, and 6% of patients, respectively. Comparison of dd-cfDNA levels in patients with CAV0 and CAV1-2-3 (primary end-point) did not show significant differences (0.92%, IQR 0.46-2.0 vs. 0.46%, IQR 0.075-1.5, p = 0.059), nor did the comparison between patients with stable CAV (no new coronary lesions since previous angiogram, n = 77) and progressive CAV (n = 17); dd-cfDNA values 0.735% (IQR 0.195-2.0) vs. 0.9% (IQR 0.12-1.8), p = 0.76. However, we found an association between NTproBNP levels and CAV degree (p = 0.017). Dd-cfDNA levels did not correlate with NTproBNP (ρ = -0.095). Conclusion: In this study, dd-cfDNA did not perform as a useful biomarker to avoid surveillance coronary angiograms for CAV diagnosis. Clinical Trial Notation: Potential Role of Donor-derived Cell Free DNA as a Biomarker in Cardiac Allograft Vasculopathy, NCT04791852.

Assessment of UL56 Mutations before Letermovir Therapy in Refractory Cytomegalovirus Transplant Recipients.

De novo mutations in the UL56 terminase subunit and its associated phenotypes were studied in the context of cytomegalovirus (CMV) transplant recipients clinically resistant to DNA-polymerase inhibitors, naive to letermovir. R246C was the only UL56 variant detected by standard and deep sequencing, located within the letermovir-resistance-associated region (residues 230-370). R246C emerged in 2/80 transplant recipients (1 hematopoietic and 1 heart) since first cytomegalovirus replication and responded transiently to various alternative antiviral treatments in vivo. Recombinant phenotyping showed R246C conferred an advanced viral fitness and was sensitive to ganciclovir, cidofovir, foscarnet, maribavir, and letermovir. These results demonstrate a low rate (2.5%) of natural occurring polymorphisms within the letermovir-resistant-associated region before its administration. Identification of high replicative capacity variants in patients not responding to treatment or experiencing relapses could be helpful to guide further therapy and dosing of antiviral molecules. IMPORTANCE We provide comprehensive data on the clinical correlates of both CMV genotypic follow-up by standard and deep sequencing and the clinical outcomes, as well as recombinant phenotypic results of this novel mutation. Our study emphasizes that the clinical follow-up in combination with genotypic and phenotypic studies is essential for the assessment and optimization of patients experiencing HCMV relapses or not responding to antiviral therapy. This information may be important for other researchers and clinicians working in the field to improve the care of transplant patients since drug-resistant CMV infections are an important emerging problem even with the new antiviral development.

Value of advanced interatrial block in the diagnosis of the ischemic stroke's aetiology: A cohort study.

INTRODUCTION AND OBJECTIVES: Advanced interatrial block has been linked with atrial fibrillation (AF) (Bayes syndrome). On the other hand, the aetiology of the stroke remains unknown in approximately 20-25% of patients admitted due to ischaemic stroke. The aim of this study was to evaluate whether advanced interatrial block and CHADS2-VASC scale is linked to AF in patients admitted due to ischaemic stroke without previous AF history. METHODS: A prospective analysis of consecutive in-hospital patients admitted with ischemic stroke between January/2018 and April/2019 in a stroke hospital was performed. Patients had to be in sinus rhythm at admission and without previous history of AF/atrial flutter. During follow up patients receive the usual care. RESULTS: A total of 236 patients were included. The median follow-up was 540 days (407-695). 19 patients (8.1%) had advanced interatrial block at admission. Advanced interatrial block was associated with the diagnosis of AF during follow up (5 (26.3%) Vs 21 (9.7%) p=0.027). A CHADS2-VASC score>4 at admission was also associated with AF diagnosis during follow up (23(14.6%) vs 3(3.9%) p=0.009). CONCLUSION: This study confirms the association of advanced interatrial block and CHADS2-VASC>4 at admission with the diagnosis of AF during follow up in patients with ischemic stroke. This association could have important implications in patients with ischemic stroke who present advanced interatrial block and without previous history of AF.