The absence of seroconversion after exposition to hepatitis C virus is not related to KIR-HLA genotype combinations (GEHEP-012 study).

BACKGROUND & AIMS: It has been reported that specific killer-cell immunoglobulin-like receptors (KIRs) and HLA genotype combinations, such as KIR2DS4/HLA-C1 with presence of KIRDL2 or KIRDL3, homozygous KIRDL3/HLA-C1 and KIR3DL1/≥2HLA-Bw4, are strongly associated with the lack of active infection and seroconversion after exposition to hepatitis C virus (HCV). OBJECTIVE: To determine whether these KIR-HLA combinations are relevant factors involved in that phenotype. PATIENTS AND METHODS: In this retrospective case-control study, genotype data from a genome-wide association study previously performed on low susceptibility to HCV-infection carried out on 27 high-risk HCV-seronegative (HRSN) individuals and 743 chronically infected (CI) subjects were used. HLA alleles were imputed using R package HIBAG v1.2223 and KIR genotypes were imputed using the online resource KIR*IMP v1.2.0. RESULTS: It was possible to successfully impute at least one KIR-HLA genotype combination previously associated with the lack of infection and seroconversion after exposition to HCV in a total of 23 (85.2%) HRSN individuals and in 650 (87.5%) CI subjects. No KIR-HLA genotype combination analyzed was related to the HRSN condition. CONCLUSIONS: Our results suggest that those KIR-HLA genotype combinations are not relevant factors involved in the lack of infection and seroconversion after exposition to HCV. More studies will be needed to completely understand this phenotype.

Hepatic Steatosis and Weight Gain During the Coronavirus Disease 2019 Pandemic Among People With Human Immunodeficiency Virus: Impact of Therapy With Tenofovir Alafenamide.

Background: Lockdown due to the coronavirus disease 2019 (COVID-19) pandemic led to increases in weight in part of the population. Weight gain leads to hepatic steatosis (HS). Antiretroviral treatment could also influence HS in people with human immunodeficiency virus (PWH). The impact of lockdown on HS in PWH is unknown. The aim of this study was to analyze the changes in HS, as measured by the controlled attenuation parameter (CAP), during the COVID-19 pandemic in PWH. Methods: This was a cohort study that included PWH who attended a tertiary care center in southern Spain from January 2018 to December 2021. The CAP was evaluated by transient elastography. Only those who had a valid CAP before and after March 2020 were included. HS was defined as CAP ≥248 dB/m. Results: Six hundred eighty PWH were attended and 488 (71.8%) were included. Two hundred and fourteen (43.9%) had HS at baseline and 239 (49%) at the end of the follow-up (P = .036). The median change in CAP among PWH taking tenofovir alafenamide (TAF) was 8.5 (interquartile range [IQR], -24 to 46.3) dB/m versus -4 (IQR, -35 to 27) dB/m among PWH receiving TAF-free regimens (P = .003). After multivariate analysis, adjusted by sex and age, weight gain (adjusted odds ratio [AOR], 1.09 [95% confidence interval {CI}, 1.05-1.14]; P < .001), TAF therapy (AOR, 1.59 [95% CI, 1.07-2.35]; P = .021), plasma triglycerides (AOR, 1.01 [95% CI, 1-1.01]; P < .001), and fasting blood glucose (AOR, 1.01 [95% CI, 1-1.02]; P = .027) were associated with HS at the end of follow-up. Conclusions: The frequency of HS increased during the COVID-19 pandemic among PWH. TAF is associated with HS development, regardless of metabolic factors.

SARS-CoV-2 viral RNA detection using the novel CoVradar device associated with the CoVreader smartphone app.

The COVID-19 pandemic has highlighted the need for innovative approaches to its diagnosis. Here we present CoVradar, a novel and simple colorimetric method that combines nucleic acid analysis with dynamic chemical labeling (DCL) technology and the Spin-Tube device to detect SARS-CoV-2 RNA in saliva samples. The assay includes a fragmentation step to increase the number of RNA templates for analysis, using abasic peptide nucleic acid probes (DGL probes) immobilized to nylon membranes in a specific dot pattern to capture RNA fragments. Duplexes are formed by labeling complementary RNA fragments with biotinylated SMART bases, which act as templates for DCL. Signals are generated by recognizing biotin with streptavidin alkaline phosphatase and incubating with a chromogenic substrate to produce a blue precipitate. CoVradar results are analysed by CoVreader, a smartphone-based image processing system that can display and interpret the blotch pattern. CoVradar and CoVreader provide a unique molecular assay capable of detecting SARS-CoV-2 viral RNA without the need for extraction, preamplification, or pre-labeling steps, offering advantages in terms of time (∼3 h/test), cost (∼€1/test manufacturing cost) and simplicity (does not require large equipment). This solution is also promising for developing assays for other infectious diseases.

The role of resilience: Physical activity continuation after falling in adults with multiple sclerosis.

BACKGROUND: As activity curtailment is common after a fall, the ability to harness resiliency is particularly salient for those with multiple sclerosis (MS) who fall frequently and who significantly benefit from remaining physically active. OBJECTIVE: The purpose of the study was to identify resilience factors, coping processes, and benefit finding underscoring the continuation of physical activity after experiencing a fall in individuals with MS. METHODS: Twelve individuals with MS (seven females and five males) participated in this qualitative study. Participants were asked general questions regarding their physical activity engagement and experiences around falling. Specific questions focused on health perceptions, personal characteristics, strategies and behaviors employed after a fall that related to remaining physically active, and any positives they perceived from falling. Transcribed interviews were analyzed and semantic themes identified. RESULTS: From the data, specific protective factors, resilience processes, and benefit finding emerged to explain participant capability to bounce back and continue with physical activity after falling. These personal factors included Locus of Control, Perseverance, Positive Attitude and Optimism, and Flexibility. Resilience processes included Utilizing Support, Problem Based Coping, and Perspective Taking. Finally, the theme of Looking Beyond Oneself was identified as a benefit. CONCLUSIONS: Understanding existing resilience factors that allow an individual to remain physically active after falling can potentially inform resilience-building interventions that broaden and build resilience resources and improve psychological and physical health in those with MS.

A regular wide QRS complex tachycardia with fusion beats?

A case of wide complex tachycardia with isolated QRS complexes of different amplitude suggesting that this was ventricular tachycardia.

Isolated palpitations and ventricular pre-excitation.

A 27-year-old male was referred for further assessment after being evaluated by his general practitioner for isolated palpitations. A twelve-lead electrocardiogram was performed in which sinus rhythm with ventricular pre-excitation were observed. Electrophysiologic study demonstrated the presence of a fasciculoventricular accessory pathway.

Elevated soluble TNFα levels and upregulated TNFα mRNA expression in purified peripheral blood monocyte subsets associated with high-grade hepatocellular carcinoma.

BACKGROUND: Chronic inflammation is involved in the initiation and progression of various cancers, including liver cancer. The current study focuses on the characterization of the peripheral immune response in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) patients, before and after surgical procedure, in order to assess the effect of tumor resection in the immune system homeostasis and to determine possible prognostic factors associated with high-grade tumors. We developed a whole-blood assay to monitor immune alterations and functional competence of peripheral monocytes in a group of 10 healthy individuals (HG), in 20 HCC patients and 8 CCA patients, by multi-color flow cytometry, qRT-PCR, and ELISA techniques. RESULTS: The qRT-PCR analysis showed an upregulation of TNFα expression by classical and intermediate monocytes purified from HCC patients presenting tumors in grade G3-G4 as compared to G1-G2 HCC patients. Moreover, ELISA assay confirmed elevated serum levels of TNFα in G3-G4 compared to G1-G2 HCC patients. A significant decrease of circulating non-classical monocytes was detected in both CCA and HCC patients before and after surgical procedure. In addition, a functional defect in circulating classical and intermediate monocytes was observed in both groups of cancer patients when compared to the HG, with partial recovery after the surgical intervention. CONCLUSIONS: This integrated analysis permitted the identification of altered functional competence of monocyte subsets in CCA and HCC patients. In addition, our results point to a potential role of TNFα as a prognostic peripheral biomarker in HCC patients, indicating the presence of high-grade tumors that should be further validated.

Respuesta al ECG de marzo de 2020 / Response to ECG, March 2020

No disponible

ECG de marzo de 2020 / ECG, March 2020

No disponible

Tumor Resection Induces Alterations on Serum Phospholipidome of Liver Cancer Patients.

Hepatocellular carcinoma and cholangiocarcinoma are the most common primary malignant liver tumors. Since the liver plays a key role in lipid metabolism, the study of serum phospholipid (PL) profiles may provide a better understanding of alterations in hepatic lipid metabolism. In this study, we used a high-resolution HILIC-LC-MS lipidomic approach to establish the serum phospholipidome profile of patients with liver cancer before (T0) and after tumor resection (T1) and a control group (CT) of healthy individuals. After the analysis of PL profiles, we observed that the phospholipidome of patients with liver cancer was significantly modified after the tumor resection procedure. We observed an upregulation of some phosphatidylcholine (PtdCho) species, namely, PtdCho(36:6), PtdCho(42:6), PtdCho(38:5), PtdCho(36:5), PtdCho(38:6) and choline plasmalogens (PlsCho), and/or 1-O-alkyl-2-acyl-glycerophosphocholine (PakCho) in patients with liver cancer at T0 compared to the CT group, and a downregulation after tumor resection (T1) when compared to T0. These results show that LC-MS can detect different serum PL profiles in patients with liver cancer, before and after tumor resection, by defining a specific PL fingerprint that was used to determine the effect of tumor and tumor resection on lipid metabolism.

Impact of routine right parasternal electrocardiographic screening in assessing eligibility for subcutaneous implantable cardioverter-defibrillator.

INTRODUCTION: Between 7% and 15% of patients with an indication for an implantable cardioverter-defibrillator (ICD) are not eligible for implantation of a subcutaneous implantable cardioverter-defibrillator (S-ICD) on the basis of the result of the conventional left parasternal electrocardiographic screening (LPES). Our objective was to determine the impact of systematically performing right parasternal electrocardiographic screening (RPES) in addition to conventional LPES, in terms of increasing both the total percentage of potentially eligible patients for S-ICD implantation and the number of suitable vectors per patient. METHODS AND RESULTS: Consecutive patients from the outpatient device clinic who already had an implanted ICD, and no requirement for pacing were enrolled. Conventional left parasternal electrode position and right parasternal electrode positions were used. The automatic screening tool was used to analyze the recordings. Screenings were performed in the supine and standing positions. Overall, 209 patients were included. The mean age was 63.4 ± 13 years, 59.8% had ischemic heart disease, mean QRS duration was 100 ± 31 ms, and 69.9% had a primary prevention ICD indication. Based on conventional isolated LPES, 12.9% of patients were not eligible for S-ICD compared with 11.5% based on RPES alone (P = .664). Considering LPES and RPES together, only 7.2% of patients were not eligible for S-ICD (P < .001). Moreover, the number of patients with more than one suitable vector increased from 66.5% with isolated LPES to 82.3% (23.7% absolute increase [P < .001]). CONCLUSION: Adding an automated RPES to the conventional automated LPES increased patient eligibility for the S-ICD significantly. Moreover, combined screening increased the number of suitable vectors per eligible patient.

Functional and Phenotypic Characterization of Tumor-Infiltrating Leukocyte Subsets and Their Contribution to the Pathogenesis of Hepatocellular Carcinoma and Cholangiocarcinoma.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) represent the most common primary liver malignancies whose outcome is influenced by the immune response. In the present study, we evaluated the tumor-infiltrating leukocyte (TIL) populations in 21 HCC patients and 8 CCA patients by flow cytometry immediately after the surgical procedure. Moreover, CD4+ T cells, CD8+ T cells, monocytes, and macrophages were purified by cell sorting for further analysis of gene expression by quantitative reverse-transcription polymerase chain reaction. Regarding tumor-infiltrating macrophages, we observed a significantly higher expression of markers associated with M2 phenotype and a higher expression of PD-L1 in patients with HCC in comparison to CCA. In addition, for HCC patients, we found a significant increase in the expression of CD200R in macrophages from tumors that were in grade G3-G4 as compared to tumors in grade G1-G2. Besides, a significantly higher frequency of tumor-infiltrating lymphocytes, CD8+CD56+ T cells, and natural killer cells was detected in HCC biopsies in comparison to CCA. In summary, this study has revealed functional and phenotypic differences in TIL cell subpopulations between CCA and HCC, as well as among different histopathological grades and tumor aggressiveness degrees, and it has provided evidence to better understand the tumor immune microenvironment of CCA and HCC.

Functional Impairment of Circulating FcεRI+ Monocytes and Myeloid Dendritic Cells in Hepatocellular Carcinoma and Cholangiocarcinoma Patients.

BACKGROUND: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) represent the most common primary liver malignancies whose outcome is influenced by the immune response. METHODS: In this study, we have functionally characterized, by flow cytometry, circulating myeloid dendritic cells (mDCs) and FcεRI+ monocytes in a group of healthy individuals (n = 10) and in a group of patients with HCC (n = 19) and CCA (n = 8), at the time point of the surgical resection (T0) and once the patient had recovered from surgery (T1). Moreover, we proceeded to a more in depth phenotypic characterization of the FcεRI+ monocyte subpopulation. RESULTS: A significant decrease in the frequency of TNFα producing FcεRI+ monocytes and mDCs in HCC and CCA patients when compared to the group of healthy individuals was observed, and a close association between FcεRI+ monocytes and mDCs dysfunction was identified. In addition, the phenotypic characteristics of FcεRI+ monocytes from healthy individuals strongly suggest that this population drives to mDCs, which matches with the fact that both populations are functionally affected. CONCLUSIONS: The frequency and the function of circulating mDCs and FcεRI+ monocytes are affected in both HCC and CCA patients, and FcεRI+ monocytes could represent those fated to become mDCs. © 2019 International Clinical Cytometry Society.

A scoring algorithm for the accurate differential diagnosis of regular wide QRS complex tachycardia.

BACKGROUND: The differential diagnosis of regular wide QRS complex tachycardia (RWQRST) remains the subject of numerous publications, all of which aim at diagnosis during the acute phase. Although an accurate diagnosis is necessary to make long-term decisions, it often leads to invasive testing. METHODS: Criteria with high positive predictive values (PPVs) for diagnosis can be obtained by analyzing the electrocardiogram (ECG) data during RWQRST and comparing them with these data at baseline. By assigning points to these criteria, a scoring algorithm to accurately diagnose numerous patients can be obtained. A total of 352 consecutive patients with RWQRST were included. Two electrophysiologists blind to patient condition analyzed the 16 criteria considered as having high PPVs. RESULTS: A total of 149 (42.3%) cases were supraventricular tachycardia (SVT), and 203 (57.7%) cases were ventricular tachycardia (VT). A higher percentage of patients with VT had structural heart disease (86.7% vs 16.1%). Seven of the 16 criteria analyzed had PPVs > 95%, and each criterion was assigned a score. A final score of -1 was indicative of SVT (PPV 98%); a score of 1 was indicative of VT (PPV 98%); and a score of ≥2 was indicative of VT (PPV 100%). A score of ≠0 was obtained for 51.7% of all cases of tachycardia, making it possible to reach a highly accurate diagnosis in approximately half of all cases. No cases of VT scored -1, and no cases of SVT scored ≥2. CONCLUSIONS: The current scoring system stands out for its high PPV (98%) and specificity (98%), enabling an accurate diagnosis for more than half of the patients.