SARS-CoV-2 Infection and Anemia-A Focus on RBC Deformability and Membrane Proteomics-Integrated Observational Prospective Study.

INTRODUCTION: The multifaceted impact of COVID-19 extends beyond the respiratory system, encompassing intricate interactions with various physiological systems. This study elucidates the potential association between SARS-CoV-2 infection and anemia, with a particular emphasis on the deformability of red blood cells (RBCs), stability of hemoglobin, enzymatic activities, and proteomic profiles. METHODS: The study encompasses a cohort of 74 individuals, including individuals positive for COVID-19, a control group, and patients with other viral infections to discern the specific effects attributable to COVID-19. The analysis of red blood cells was focused on deformability measured by osmotic gradient ektacytometry, hemoglobin stability, and glycolytic enzyme activity. Furthermore, membrane proteins were examined using advanced proteomics techniques to capture molecular-level changes. RESULTS: Findings from the study suggest a correlation between anemia and exacerbated outcomes in COVID-19 patients, marked by significant elevations in d-dimer, serum procalcitonin, creatinine, and blood urea nitrogen (BUN) levels. These observations suggest that chronic kidney disease (CKD) may play a role in the development of anemia in COVID-19 patients, particularly those of advanced age with comorbidities. Furthermore, the proteomic analyses have highlighted a complex relationship between omics data and RBC parameters, enriching our understanding of the mechanisms underlying the disease. CONCLUSIONS: This research substantiates the complex interrelationship between COVID-19 and anemia, with a specific emphasis on the potential repercussions of SARS-CoV-2 infection on RBCs. The findings contribute to the growing body of evidence supporting the extensive impact of COVID-19 on RBCs.

Left bundle branch pacing versus left ventricular septal pacing as a primary procedural endpoint during left bundle branch area pacing: Evaluation of two different implant strategies.

INTRODUCTION: Implant procedure features and clinical implications of left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) have not been yet fully described. We sought to compare two different left bundle branch area pacing (LBBAP) implant strategies: the first one accepting LVSP as a procedural endpoint and the second one aiming at achieving LBBP in every patient in spite of evidence of previous LVSP criteria. METHODS: LVSP was accepted as a procedural endpoint in 162 consecutive patients (LVSP strategy group). In a second phase, LBBP was attempted in every patient in spite of achieving previous LVSP criteria (n = 161, LBBP strategy group). Baseline patient characteristics, implant procedure, and follow-up data were compared. RESULTS: The final capture pattern was LBBP in 71.4% and LVSP in 24.2% in the LBBP strategy group compared to 42.7% and 50%, respectively, in the LVSP strategy group. One hundred and eighty-four patients (57%) had proven LBB capture criteria with a significantly shorter paced QRS duration than the 120 patients (37%) with LVSP criteria (115 ± 9 vs. 121 ± 13 ms, p < .001). Implant parameters were comparable between the two strategies but the LBBP strategy resulted in a higher rate of acute septal perforation (11.8% vs. 4.9%, p = .026) without any clinical sequelae. Patients with CRT indications significantly improved left ventricular ejection fraction (LVEF) during follow-up irrespective of the capture pattern (from 35 ± 11% to 45 ± 14% in proven LBBP, p = .024; and from 39 ± 13% to 47 ± 12% for LVSP, p = .003). The presence of structural heart disease and baseline LBBB independently predicted unsuccessful LBB capture. CONCLUSION: The LBBP strategy was associated with comparable implant parameters than the LVSP strategy but resulted in higher rates of septal perforation. Proven LBB capture and LVSP showed comparable effects on LVEF during follow-up.

Conduction System Pacing for Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) via biventricular pacing (BiVP-CRT) is considered a mainstay treatment for symptomatic heart failure patients with reduced ejection fraction and wide QRS. However, up to one-third of patients receiving BiVP-CRT are considered non-responders to the therapy. Multiple strategies have been proposed to maximize the percentage of CRT responders including two new physiological pacing modalities that have emerged in recent years: His bundle pacing (HBP) and left bundle branch area pacing (LBBAP). Both pacing techniques aim at restoring the normal electrical activation of the ventricles through the native conduction system in opposition to the cell-to-cell activation of conventional right ventricular myocardial pacing. Conduction system pacing (CSP), including both HBP and LBBAP, appears to be a promising pacing modality for delivering CRT and has proven to be safe and feasible in this particular setting. This article will review the current state of the art of CSP-based CRT, its limitations, and future directions.

A pandemic momentum index to manage the spread of COVID-19.

Quantifying the spreading power of a pandemic like COVID-19 is important for the early implementation of early restrictions on social mobility and other interventions to slow its spread. This work aims to quantify the power of spread, defining a new indicator, the pandemic momentum index. It is based on the analogy between the kinematics of disease spread and the kinematics of a solid in Newtonian mechanics. This index, I PM , is useful for assessing the risk of spread. Based on the evolution of the pandemic in Spain, a decision-making scheme is proposed that allows early responses to the spread and decreases the incidence of the disease. This index has been calculated retrospectively for the pandemic in Spain, and a counterfactual analysis shows that if the decision-making scheme had been used as a guide, the most significant decisions on restrictions would have been advanced: the total number of confirmed cases of COVID-19 would have been much lower during the period studied, with a significant reduction in the total number of cases: 83 % (sd = 2.6). The results of this paper are consistent with the numerous studies on the pandemic that concluded that the early implementation of restrictions is more important than their severity. Early response slows the spread of the pandemic by applying less severe mobility restrictions, reducing the number of cases and deaths, and doing less damage to the economy.

Mechanoresponsive Drug Delivery Systems for Vascular Diseases.

Mechanoresponsive drug delivery systems (DDS) have emerged as promising candidates to improve the current effectiveness and lower the side effects typically associated with direct drug administration in the context of vascular diseases. Despite tremendous research efforts to date, designing drug delivery systems able to respond to mechanical stimuli to potentially treat these diseases is still in its infancy. By understanding relevant biological forces emerging in healthy and pathological vascular endothelium, it is believed that better-informed design strategies can be deduced for the fabrication of simple-to-complex macromolecular assemblies capable of sensing mechanical forces. These responsive systems are discussed through insights into essential parameter design (composition, size, shape, and aggregation state) , as well as their functionalization with (macro)molecules that are intrinsically mechanoresponsive (e.g., mechanosensitive ion channels and mechanophores). Mechanical forces, including the pathological shear stress and exogenous stimuli (e.g., ultrasound, magnetic fields), used for the activation of mechanoresponsive DDS are also introduced, followed by in vitro and in vivo experimental models used to investigate and validate such novel therapies. Overall, this review aims to propose a fresh perspective through identified challenges and proposed solutions that could be of benefit for the further development of this exciting field.

Acute performance of stylet driven leads for left bundle branch area pacing: A comparison with lumenless leads.

Background: Lumenless leads (LLLs) are widely used for left bundle branch area pacing (LBBAP). Recently, stylet-driven leads (SDLs) have also been used for LBBAP. Objective: The purpose of this study was to evaluate the acute performance of SDLs during LBBAP in comparison with LLLs. Methods: Consecutive patients undergoing LBBAP for bradycardia or cardiac resynchronization therapy indications at 2 high-volume, early conduction system pacing adopters, tertiary centers were included from January 2019 to July 2023. Patients received either SDLs or LLLs at the discretion of the implanting physician. Acute performance and follow-up data of both lead types were evaluated. Results: A total of 925 LBBAP implants were included, 655 using LLLs and 270 using SDLs. Overall, LBBAP acute success was significantly higher with LLLs than SDLs (95.3% vs 85.1%, respectively; P <.001) even after the learning curve (97% vs 86%; P = .013). LLLs were implanted in more mid-basal septal positions in comparison with SDLs, which tended to be implanted in more inferior and mid-apical septal positions. Acute lead-related complications were higher with SDLs than LLLs (15.9% vs 6.1%, respectively; P <.001) with 15 cases of lead damage during implant (4.4% vs 0.5%; P <.001) but decreased with acquired experience and were comparable in the last 100 patients included in each group. Lead implant and fluoroscopy times were shorter for SDLs, with lead dislodgment occurring in 0.9% with LLLs and 1.5% with SDLs (P = .489). Conclusion: Acute lead performance proved to be different between LLLs and SDLs. A specific learning curve should be considered for SDLs even for implanters with extensive previous experience with LLLs.

A case of CD138-/CD19+/CD4+ IgD plasma cell leukemia.

BACKGROUND: Plasma cell leukemia (PCL) is an uncommon and aggressive disease caused by the clonal proliferation of atypical plasma cells with phenotypical abnormalities similar to those seen in multiple myeloma (MM), although at different rates. Here, we report a case of IgD PCL with a very unusual CD138-/CD19+/CD4+ phenotype. METHODS: Peripheral blood and bone marrow samples from a 37-year-old patient afflicted by an aggressive plasma cell dyscrasia were examined and analyzed by conventional morphology, flow cytometry, and immunohistochemistry. RESULTS: Analysis of peripheral blood fulfilled criteria for PCL (more than 20% and more than 2 × 10e9 cells/L). However, flow cytometry and immunohistochemistry phenotyping revealed that the cells were CD138-/CD38+/CD19+/CD4+/CD56-/CD117-. CONCLUSIONS: PCL is diagnosed on peripheral blood smear. Immunophenotyping is a tool that can be helpful in diagnosing difficult cases but its atypical findings should not prevent the appropriate PCL diagnosis in clinically and morphologically unquestionable cases. © 2014 International Clinical Cytometry Society.

A case of CD138-/CD19+/CD4+ IgD plasma cell leukemia.

Background: Plasma cell leukemia (PCL) is an uncommon and aggressive disease caused by the clonal proliferation of atypical plasma cells with phenotypical abnormalities similar to those seen in multiple myeloma (MM), although at different rates. Here we report a case of IgD PCL with a very unusual CD138-/CD19+/CD4+ phenotype Methods: Peripheral blood and bone marrow samples from a 37 year old patient afflicted by an aggressive plasma cell dyscrasia were examined and analyzed by conventional morphology, flow cytometry and immunohistochemistry. Results: Analysis of peripheral blood fulfilled criteria for PCL (more than 20% and more than 2x10e9 cells/L). However, flow cytometry and immunohistochemistry phenotyping revealed that the cells were CD138-/CD38+/CD19+/CD4+/CD56-/CD117- Conclusion: PCL is diagnosed on peripheral blood smear. Immunophenotyping is a tool that can be helpful in diagnosing difficult cases but its atypical findings should not prevent the appropriate PCL diagnosis in clinically and morphologically unquestionable cases. © 2014 Clinical Cytometry Society.

Adult T-cell leukemia/lymphoma with an unusual CD1a positive phenotype.

BACKGROUND: Acute T-cell leukemia lymphoma (ATLL) tumor cells generally express CD2/CD3/CD5, but lack CD7. These T cells are usually CD4+CD8- and strongly express CD25, although some variability in this basic pattern may be found. Here we report a case with a very unusual CD1a positive phenotype. METHODS: Samples from peripheral blood, bone marrow aspirate, lymph node, and cerebrospinal fluid obtained from a 45-year-old male patient with a T-cell lymphoproliferative disorder were immunophenotyped by multiparametric flow cytometry. Analysis of HTLV-I genome integration in tumoral cells was performed by PCR. RESULTS: Neoplastic T cells were cCD3, CD2/CD5/CD30/CD25, and CD1a positive, but CD3/CD7/CD4/CD8/CD34/CD10/TdT negative. Serology and integration of HTLV-I were positive. CONCLUSION: To the best of our knowledge, CD1a expression has not been previously described in this entity. Its detection raised the differential diagnosis with acute T lymphoblastic leukemia. The rest of the phenotypic markers, the morphology of the neoplastic cells, and the demonstration of HTLV-I genome integration provided the final diagnosis.

Adult T-cell leukemia/lymphoma with an unusual CD1a positive phenotype.

Background: Acute T-cell leukemia lymphoma (ATLL) tumor cells generally express CD2/CD3/CD5, but lack CD7. These T cells are usually CD4+CD8- and strongly express CD25, although some variability in this basic pattern may be found. Here we report a case with a very unusual CD1a positive phenotype. Methods: Samples from peripheral blood, bone marrow aspirate, lymph node and CSF obtained from a 45 year old male patient with a T-cell lymphoproliferative disorder were immunophenotyped by multiparametric flow cytometry Analysis of HTLV-I genome integration in tumoral cells was performed by PCR. Results: Neoplastic T cells were cCD3, CD2/CD5/CD30/CD25 and CD1a positive, but CD3/CD7/CD4/CD8/CD34/CD10/TdT negative. Serology and integration of HTLV-I were positive. Conclusion: To the best of our knowledge CD1a expression has not been previously described in this entity. Its detection raised the differential diagnosis with acute T lymphoblastic leukemia. The rest of the phenotypic markers, the morphology of the neoplastic cells, and the demonstration of HTLV-I genome integration provided the final diagnosis. © 2013 Clinical Cytometry Society.

Drug-eluting stents for off-label indications in real clinical world: evidence based or 'intuition' based clinical practice?

BACKGROUND: The use of drug-eluting stents (DES) is an example of the disparity between recommendations given by regulatory agencies and the real clinical world. Such disparity might lead cardiologists to adopt different routines in the use of DES. We aimed to assess variability of off-label DES use between hospitals and to what extent it can be explained by differences in patient or hospital characteristics. METHODS: Characteristics of consecutive patients receiving DES in 29 hospitals were recorded. Individual and hospital determinants of receiving DES for off-label indications were assessed by multilevel logistic regression. RESULTS: 1903 patients were recruited and 1188 (62.4%) received DES for off-label indications. Individual variables associated with off-label use were age (OR 1.01 (1-1.02)), previous percutaneous (OR 2.24 (1.68-2.97)) or surgical (2.41 (1.52-3.84)) revascularization, repeated procedure at the same admission (OR 4.66 (2.7-8.05)), receiving two (OR 4.17 (3.24-5.37)) or three or more DES (OR 14.12 (9.08-21.96)) vs one. Adjusting for individual variables, the Odds of receiving DES for off-label indication was higher in public funding hospitals with surgery availability vs private hospitals: 1.49 (0.86-2.6), and in public hospitals without surgery vs public with surgery availability: OR 1.76 (1.02-3.03). Interhospital variability reminded significant after adjustment for individual and contextual variables. CONCLUSION: Off-label DES use is highly variable between centers. Although this variability is partially determined by hospital type of funding and cardiac surgery availability, the substantial interhospital variability after multilevel adjustment suggests heterogeneity in the process of care.

Scoring systems in mantle cell lymphoma: a critical point of view.

A proposal for a scoring system in the diagnosis of chronic lymphoproliferative diseases other than CLL has been recently published in Cytometry Part B. The authors apply this score for deciding whether or not FISH evaluation for the detection of IGH/CCND1 rearrangements must be performed to exclude Mantle Cell Lymphoma (MCL). In their validation series, no MCL scored <3. We have applied their system to our cases of MCL and also to a small series of Marginal Zone lymphomas. In our hands, the scoring system as has been published does not discriminate adequately between both entities. We propose using the negativity of a marker, CD11c, instead of the platelet count to improve the results. However, we believe that given the clinical and prognostic implications of the diagnosis of MCL, scoring systems should be greatly ameliorated prior to their generalized use.

[Arrhythmogenic cardiomyopathy. Patterns of ventricular involvement using cardiac magnetic resonance]. / Resonancia magnética cardiaca en miocardiopatía arritmogénica. Tipos de afección y patrones de realce tardío de gadolinio.

INTRODUCTION AND OBJECTIVES: Biventricular arrhythmogenic cardiomyopathy and left dominant arrhythmogenic cardiomyopathy forms had recently been included in the spectrum of arrhythmogenic cardiomyopathy. The aim of the study was to describe, using cardiovascular magnetic resonance, the patterns of ventricular involvement as well as late gadolinium enhancement in these conditions. METHODS: Medical databases and records from the cardiology units of 3 hospitals were reviewed to obtain data from patients with arrhythmogenic cardiomyopathy. RESULTS: Twenty-six consecutive patients were included (40 [16] years, 16 males). Right ventricle involvement was present in 19 patients (73%). Among them, 13 patients (50%) had volumes over the upper limit of normality, 11 (42%) patients had late gadolinium enhancement in right ventricle and 6 patients (23%) had just mild involvement with wall motion abnormalities or microaneurysms. Left ventricle involvement was present in 24 patients (92%), all of them with late gadolinium enhancement. In 15 patients (57%) left ventricular systolic dysfunction was observed, and dilatation in 3 patients (11%). Late gadolinium enhancement was more frequent in the inferior, lateral, and inferolateral walls (65%, 57%, and 61% of patients, respectively) while septum was seldom affected (26% of cases). The pattern of late gadolinium enhancement was mainly subepicardial (46% of patients) or transmural (19%), and was intramyocardial in only 12% of the cases. CONCLUSIONS: In this sample, left ventricle involvement is very common. The most frequent finding was left ventricular late gadolinium enhancement, while the least frequent was dilatation. The pattern of late gadolinium enhancement was more frequently subepicardial and located in the inferior and inferolateral walls.

Technical reliability and clinical safety of a remote monitoring system for antiarrhythmic cardiac devices.

INTRODUCTION AND OBJECTIVES: In recent years, physicians have experienced a huge increase in workload associated with cardiac devices. Remote monitoring enables these devices to be monitored at a distance and could reduce the number of hospital visits. The aim of this study was to assess the technical reliability and clinical safety of the Home MonitoringTM remote monitoring system (Biotronik GmbH, Germany). METHODS: The study included 162 patients: 115 with pacemakers, 44 with implantable cardioverter-defibrillators (ICDs) and three with ICDs incorporating cardiac resynchronization therapy (CRT). Patients were followed up for a mean of 303+/-244 days. We compared the survival time free of event alerts in patients with pacemakers and in those with ICDs. The remote monitoring system's reliability was evaluated by comparing the data it transmitted with clinical observations made immediately afterwards. RESULTS: The mean percentage of days monitored was 88.2%. The incidence of event alerts was higher in pacemaker than ICD patients (45% vs. 34%; P=.01). Event alerts preceded the following hospital visit by 76+/-47 days. In the ICD group, the data sent by the monitoring system were judged as true-positives in 42% of cases, as true-negatives in 57% and as false-positives in 1%. No false-negative was observed. In the ICD group, the remote monitoring system had a sensitivity of 100% and a specificity of 97% (positive predictive value 96%, negative predictive value 100%). CONCLUSIONS: Remote monitoring was a reliable and safe method for following up patients with cardiac devices. Its routine use could enable the early detection of device malfunctions or arrhythmic events.