scholarly journals When Manual Analysis of 12-Lead ECG Holter Plays a Critical Role in Discovering Unknown Patterns of Increased Arrhythmogenic Risk: A Case Report of a Patient Treated with Tamoxifen and Subsequent Pneumonia in COVID-19

2021 ◽  
Author(s):  
Donatella Brisinda ◽  
Barbara Merico ◽  
Peter Fenici ◽  
Riccardo Fenici
Keyword(s):  
Ventricular Myocytes ◽  
Therapeutic Option ◽  
Critical Role ◽  
Holter Monitoring ◽  
Ventricular Repolarization ◽  
Cancer Therapies ◽  
Qtc Interval ◽  
Increased Risk ◽  
Repolarization Reserve ◽  
Life Threatening

AbstractSeveral medicines, including cancer therapies, are known to alter the electrophysiological function of ventricular myocytes resulting in abnormal prolongation and dispersion of ventricular repolarization (quantified by multi-lead QTc measurement). This effect could be amplified by other concomitant factors (e.g., combination with other drugs affecting the QT, and/or electrolyte abnormalities, such as especially hypokalemia, hypomagnesaemia, and hypocalcemia). Usually, this condition results in higher risk of torsade de point and other life-threatening arrhythmias, related to unrecognized unpaired cardiac ventricular repolarization reserve (VRR). Being VRR a dynamic phenomenon, QT prolongation might often not be identified during the 10-s standard 12-lead ECG recording at rest, leaving the patient at increased risk for life-threatening event. We report the case of a 49-year woman, undergoing tamoxifen therapy for breast cancer, which alteration of ventricular repolarization reserve, persisting also after correction of concomitant recurrent hypokalemia, was evidenced only after manual measurements of the corrected QT (QTc) interval from selected intervals of the 12-lead ECG Holter monitoring. This otherwise missed finding was fundamental to drive the discontinuation of tamoxifen, shifting to another “safer” therapeutic option, and to avoid the use of potentially arrhythmogenic antibiotics when treating a bilateral pneumonia in recent COVID-19.

Abstract P230: Metabolically Healthy Obesity and QT interval. The Polish Norwegian Study

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Georgeta Vaidean ◽  
Marta Manczuk ◽  
Jared W Magnani
Keyword(s):  
Qt Interval ◽  
Large Population ◽  
Ventricular Repolarization ◽  
Qtc Interval ◽  
Benign Condition ◽  
Metabolically Healthy Obese ◽  
Increased Risk ◽  
Healthy Obese ◽  
Metabolically Healthy ◽  
Age And Sex

Introduction: Obesity has been linked to increased risk of sudden cardiac death and ventricular arrhythmia. Whether the metabolically healthy obese phenotype is a benign condition, is debatable and few studies examined its ventricular repolarization profile. Purpose: To examine the association of metabolically healthy/unhealthy obesity phenotypes with prolonged corrected QT (QTc) interval in a large population-based study. Methods: Cross-sectional data from an ongoing cohort study in Poland. Data was collected using a standardized protocol. The QT intervals were obtained from digital standard 12-lead resting ECG and were corrected for heart rate by Bazett’s formula. Plasma lipids and glucose were measured in a fasting state. After excluding drugs known to affect the QT interval (antiarrhythmics, digoxin, antipsychotics), the analytic sample size was 11068 participants, ages 45 to 64 years. Based on the presence of obesity (BMI ge 30 kg/ m 2 ) and metabolic syndrome (per the AHA/NHLBI harmonized definition), we defined four phenotypes: metabolically healthy non-obese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Multivariable linear and logistic regression models were used for analyses. Results: The prevalence of the 4 phenotypes was: MHNO: 51.34%, MUNO: 18.07%, MHO: 10.07%, MUO: 20.52%. The prevalence of an increased QTc interval (greater than >430ms in men/450ms in women) was 14.28%, and the prevalence of a highly prolonged QTc interval (greater than 450ms in men/470ms in women) was 5.2%. The age- and sex-adjusted mean QTc across the 4 phenotypes was: MHNO: 417.05ms (416.39- 417.71; MUNO: 418.82 ms (417.71-419.92); MHO: 420.46 ms (418.99 -421.93); MUO: 422.45 ms (421.41-423.49). The age- and sex adjusted odds (OR, 95% CI) of an increased QTc interval (greater than 430/450ms in men/women) were increased in MUNO (1.11, 0.96-1.29), MHO (1.44, 1.20-1.72) and MUO (1.47, 1.28-1.69), compared to MHNO phenotype. These estimates were minimally attenuated after additional adjustment for prevalent CVD, LVH on ECG, smoking, alcohol intake, physical activity and education: MUNO (1.10, 0.94-1.28), MHO (1.45, 1.21-1.73) and MUO (1.44, 1.26-1.66). We did not detect effect modification by sex. We obtained similar results in subgroup analyses restricted to those without diabetes and after excluding those with third degree atrioventricular blocks or conduction abnormalities with QRS>120ms. Conclusion: Both metabolically healthy- and non-healthy obese phenotypes had a higher likelihood of an increased/borderline QTc interval compared to the MHNO phenotype. Our study furthered our understanding of ventricular repolarization as reflected in the QTc interval, in the setting of different obesity phenotypes.

scholarly journals Coagulation abnormalities in SARS-CoV-2 infection: overexpression tissue factor

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Zahra Eslamifar ◽  
Mahin Behzadifard ◽  
Masoud Soleimani ◽  
Saba Behzadifard
Keyword(s):  
Tissue Factor ◽  
Proinflammatory Cytokines ◽  
Viral Infections ◽  
Multiorgan Failure ◽  
Critical Role ◽  
Coagulation Cascade ◽  
Coagulation System ◽  
Alveolar Cells ◽  
Increased Risk ◽  
Life Threatening

AbstractAmong the pathways and mediators that may be dysregulated in COVID-19 infection, there are proinflammatory cytokines, lymphocyte apoptosis, and the coagulation cascade. Venous and arterial thromboembolisms also are frequent in COVID-19 patients with the increased risk of some life-threatening complications such as pulmonary embolism, myocardial infarction, and ischemic stroke. In this regard, overproduction of proinflammatory cytokines such as IL-6, IL-1β, and TNF-α induce cytokine storms, increase the risk of clot formation, platelet activation, and multiorgan failure that may eventually lead to death among these patients. Surface S protein of SARS-CoV-2 binds to its target transmembrane receptor, named as angiotensin converting enzyme 2 (ACE2(, on various cells such as lymphocyte, alveolar cells, monocytes/macrophages, and platelets. Notably, the activation of the coagulation cascade occurs through tissue factor (TF)/FVIIa-initiated hemostasis. Accordingly, TF plays the major role in the activation of coagulation system during viral infection. In viral infections, the related coagulopathy multiple factors such as inflammatory cytokines and viral specific TLRs are involved, which consequently induce TF expression aberrantly. SARS-COV-2 may directly infect monocytes/ macrophages. In addition, TF expression/release from these cells may play a critical role in the development of COVID-19 coagulopathy. In this regard, the use of TF- VIIa complex inhibitor may reduce the cytokine storm and mortality among COVID-19 patients.

scholarly journals Structure, Function, and Regulation of the Essential Virulence Factor Capsular Polysaccharide of Vibrio vulnificus

2020 ◽  
Vol 21 (9) ◽  
pp. 3259 ◽  
Author(s):  
Gregg S. Pettis ◽  
Aheli S. Mukerji
Keyword(s):  
Coastal Waters ◽  
Capsular Polysaccharide ◽  
Vibrio Vulnificus ◽  
Critical Role ◽  
Phase Variation ◽  
Innate Immune ◽  
Repeat Sequences ◽  
Life Threatening ◽  
Inflammatory Cytokine Response ◽  
Group 1

Vibrio vulnificus populates coastal waters around the world, where it exists freely or becomes concentrated in filter feeding mollusks. It also causes rapid and life-threatening sepsis and wound infections in humans. Of its many virulence factors, it is the V. vulnificus capsule, composed of capsular polysaccharide (CPS), that plays a critical role in evasion of the host innate immune system by conferring antiphagocytic ability and resistance to complement-mediated killing. CPS may also provoke a portion of the host inflammatory cytokine response to this bacterium. CPS production is biochemically and genetically diverse among strains of V. vulnificus, and the carbohydrate diversity of CPS is likely affected by horizontal gene transfer events that result in new combinations of biosynthetic genes. Phase variation between virulent encapsulated opaque colonial variants and attenuated translucent colonial variants, which have little or no CPS, is a common phenotype among strains of this species. One mechanism for generating acapsular variants likely involves homologous recombination between repeat sequences flanking the wzb phosphatase gene within the Group 1 CPS biosynthetic and transport operon. A considerable number of environmental, genetic, and regulatory factors have now been identified that affect CPS gene expression and CPS production in this pathogen.

scholarly journals DNA methylome signatures of prenatal exposure to synthetic glucocorticoids in hippocampus and peripheral whole blood of female guinea pigs in early life

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aya Sasaki ◽  
Margaret E. Eng ◽  
Abigail H. Lee ◽  
Alisa Kostaki ◽  
Stephen G. Matthews
Keyword(s):  
Dna Methylation ◽  
Whole Blood ◽  
Guinea Pigs ◽  
Critical Role ◽  
Methylation Status ◽  
Peripheral Tissues ◽  
Epigenetic Biomarkers ◽  
Differentially Methylated Genes ◽  
Increased Risk ◽  
Synthetic Glucocorticoids

AbstractSynthetic glucocorticoids (sGC) are administered to women at risk of preterm delivery, approximately 10% of all pregnancies. In animal models, offspring exposed to elevated glucocorticoids, either by administration of sGC or endogenous glucocorticoids as a result of maternal stress, show increased risk of developing behavioral, endocrine, and metabolic dysregulation. DNA methylation may play a critical role in long-lasting programming of gene regulation underlying these phenotypes. However, peripheral tissues such as blood are often the only accessible source of DNA for epigenetic analyses in humans. Here, we examined the hypothesis that prenatal sGC administration alters DNA methylation signatures in guinea pig offspring hippocampus and whole blood. We compared these signatures across the two tissue types to assess epigenetic biomarkers of common molecular pathways affected by sGC exposure. Guinea pigs were treated with sGC or saline in late gestation. Genome-wide modifications of DNA methylation were analyzed at single nucleotide resolution using reduced representation bisulfite sequencing in juvenile female offspring. Results indicate that there are tissue-specific as well as common methylation signatures of prenatal sGC exposure. Over 90% of the common methylation signatures associated with sGC exposure showed the same directionality of change in methylation. Among differentially methylated genes, 134 were modified in both hippocampus and blood, of which 61 showed methylation changes at identical CpG sites. Gene pathway analyses indicated that prenatal sGC exposure alters the methylation status of gene clusters involved in brain development. These data indicate concordance across tissues of epigenetic programming in response to alterations in glucocorticoid signaling.

scholarly journals Feasibility of Proton Beam Therapy as a Rescue Therapy in Heavily Pre-Treated Retinoblastoma Eyes

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1862
Author(s):  
Eva Biewald ◽  
Tobias Kiefer ◽  
Dirk Geismar ◽  
Sabrina Schlüter ◽  
Anke Manthey ◽  
...  
Keyword(s):  
Proton Beam ◽  
Rescue Therapy ◽  
Therapeutic Option ◽  
Proton Beam Therapy ◽  
External Beam Radiation ◽  
Time Interval ◽  
Beam Radiation ◽  
Primary Tumors ◽  
Increased Risk

Despite the increased risk of subsequent primary tumors (SPTs) external beam radiation (EBRT) may be the only therapeutic option to preserve a retinoblastoma eye. Due to their physical properties, proton beam therapy (PBT) offers the possibility to use the effectiveness of EBRT in tumor treatment and to decisively reduce the treatment-related morbidity. We report our experiences of PBT as rescue therapy in a retrospectively studied cohort of 15 advanced retinoblastoma eyes as final option for eye-preserving therapy. The average age at the initiation of PBT was 35 (14–97) months, mean follow-up was 22 (2–46) months. Prior to PBT, all eyes were treated with systemic chemotherapy and a mean number of 7.1 additional treatments. Indication for PBT was non-feasibility of intra-arterial chemotherapy (IAC) in 10 eyes, tumor recurrence after IAC in another 3 eyes and diffuse infiltrating retinoblastoma in 2 eyes. Six eyes (40%) were enucleated after a mean time interval of 4.8 (1–8) months. Cataract formation was the most common complication affecting 44.4% of the preserved eyes, yet 77.8% achieved a visual acuity of >20/200. Two of the 15 children treated developed metastatic disease during follow-up, resulting in a 13.3% metastasis rate. PBT is a useful treatment modality as a rescue therapy in retinoblastoma eyes with an eye-preserving rate of 60%. As patients are at lifetime risk of SPTs consistent monitoring is mandatory.

Association between digoxin use and sudden cardiac death in individuals with the rs10494366 variant of the NOS1AP gene

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Soroush ◽  
A Aarnoudse ◽  
F Shokri ◽  
M Van Den Berg ◽  
F Ahmadizar ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Smoking Status ◽  
Adaptor Protein ◽  
Therapeutic Window ◽  
P Value ◽  
Qtc Interval ◽  
Total Study Population ◽  
Increased Risk

Abstract Background Digoxin is one of the oldest cardiovascular medications still used to treat heart failure and atrial fibrillation. Due to its narrow therapeutic window, it is associated with life threatening intoxication and arrhythmias, and with QTc-shortening. Common genetic variation in the nitric oxide synthase-1 adaptor protein (NOS1AP) has been associated with QTc interval prolongation. Purpose We investigated whether the rs10494366 variant of the NOS1AP gene modified the risk of SCD in patients using digoxin. Methods In a prospective population-based cohort study, we included data of the three cohorts, started as of January 1st, 1991 until January 1st 2014. Digoxin current use on the date of cardiac death in cases and the same day of follow-up in the remainder of the cohort was a time-dependent exposure. The main outcome was SCD defined as sudden and unexpected death as a result of cardiac causes, according to international criteria. Identification and adjudication of SCD was performed independently, before the start of this study. We used Cox proportional hazard regression analysis to investigate the associations between NOS1AP rs10494366 variant and incident SCD among digoxin users compared to non-users. Associations were adjusted for age, sex (model 1) in addition to BMI, prevalent diabetes, myocardial infarction, baseline hypertension and smoking status (past, current, never) (model 2). Results We included 14,594 individuals, with a mean age of 65.3 (SD 10.3) years. Almost 59% were female. The cumulative incidence of SCD was 9.5% (609 cases) by the end of follow up. Among them, 98 (16%) individuals were exposed to digoxin at the time of death. In model 1, NOS1AP rs10494366 variant was not associated with SCD in the total study population. However, an interaction term of the gene with the daily dose of digoxin was significantly associated with increased risk of SCD (p-value 0.0001). In model 2, the risk of SCD in current users of digoxin was 4.2 [95% CI 1.3–13.8] for the GG genotype; 2.1 [95% CI 1.1–4.2] for the GT genotype, and 1.5 [95% CI 0.7–3.2] for the TT genotype. Conclusion NOS1AP rs10494366 variant modified the risk of sudden cardiac death in users of digoxin. Our study suggests that individuals with the homozygous minor GG allele have a fourfold increased risk of sudden cardiac death. Funding Acknowledgement Type of funding source: None

scholarly journals Continuous renal replacement therapy rescued life-threatening capillary leak syndrome in an extremely-low-birth-weight premature: a case report

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Li-Fen Yang ◽  
Jia-Chang Ding ◽  
Ling-Ping Zhu ◽  
Li-Xia Li ◽  
Meng-Qi Duan ◽  
...  
Keyword(s):  
Birth Weight ◽  
Renal Replacement Therapy ◽  
Low Birth Weight ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Therapeutic Option ◽  
Capillary Leak Syndrome ◽  
Extremely Low Birth Weight ◽  
Capillary Leak ◽  
Life Threatening

Abstract Background Capillary leak syndrome (CLS) is a rare disease characterized by profound vascular leakage and presents as a classic triad of hypotension, hypoalbuminemia and hemoconcentration. Severe CLS is mostly induced by sepsis and generally life-threatening in newborns, especially in premature infants. Continuous renal replacement therapy (CRRT) plays an important role of supportive treatment for severe CLS. Unfortunately, CRRT in preterm infants has rarely been well defined. Case presentation We report the case of a 11-day-old girl with CLS caused by sepsis, who was delivered by spontaneous vaginal delivery (SVD) at gestational age of 25 weeks and 4 days, and a birth weight of 0.89 Kilograms(kg). The infant received powerful management consisting of united antibiotics, mechanical ventilation, intravenous albumin and hydroxyethyl starch infusion, vasoactive agents, small doses of glucocorticoids and other supportive treatments. However, the condition rapidly worsened with systemic edema, hypotension, pulmonary exudation, hypoxemia and anuria in about 40 h. Finally, we made great efforts to perform CRRT for her. Fortunately, the condition improved after 82 h’ CRRT, and the newborn was rescued and gradually recovered. Conclusion CRRT is an effective rescue therapeutic option for severe CLS and can be successfully applied even in extremely-low-birth-weight premature.

scholarly journals Prevalence and Determinants of Vaccine Hesitancy and Vaccines Recommendation Discrepancies among General Practitioners in French-Speaking Parts of Belgium

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 771
Author(s):  
Cathy Gobert ◽  
Pascal Semaille ◽  
Thierry Van der Schueren ◽  
Pierre Verger ◽  
Nicolas Dauby
Keyword(s):  
General Practitioners ◽  
Online Survey ◽  
Critical Role ◽  
Personal Characteristics ◽  
Vaccine Hesitancy ◽  
Patient Acceptance ◽  
Recent Experience ◽  
Average Percentage ◽  
Vaccine Recommendations ◽  
Increased Risk

General practitioners (GPs) play a critical role in patient acceptance of vaccination. Vaccine hesitancy (VH) is a growing phenomenon in the general population but also affects GPs. Few data exist on VH among GPs. The objectives of this analysis of a population of GPs in the Belgian Wallonia-Brussels Federation (WBF) were to: (1) determine the prevalence and the features of VH, (2) identify the correlates, and (3) estimate the discrepancy in vaccination’s behaviors between the GPs’ children and the recommendations made to their patients. An online survey was carried out among the population of general practitioners practicing in the WBF between 7 January and 18 March 2020. A hierarchical cluster analysis was carried out based on various dimensions of vaccine hesitancy: perception of the risks and the usefulness of vaccines as well as vaccine recommendations for their patients. A total of 251 GPs answered the survey. The average percentage of moderate to high vaccine hesitancy was 50.6%. Three factors were independently associated with increased risk of vaccine hesitancy: an age <50 years old, having no children, and having no contact with selected vaccine-preventable disease (measles, complicated influenza, chronic hepatitis B (HBV), bacterial meningitis, or cervical cancer) in the past 5 years. VH was associated with controversies on vaccines’ safety. GPs who had vaccinated their children against six diseases (MMR, meningococcus C (MenC), HBV, and HPV) tended not to recommend the same vaccines to their patients. Among GPs with all children vaccinated against HBV, only 37.5% recommended catch-up HBV immunization to their patients. In this small cohort of GP, moderate to high VH was associated with controversies on vaccines’ safety and with specific personal characteristics (age <50, no children, and no recent experience with a serious VPD). As previously reported, GPs have different vaccine prescription attitude toward their patients and children. These findings should be confirmed in larger cohorts.

scholarly journals Cardiac small-conductance calcium-activated potassium channels in health and disease

2021 ◽  
Vol 473 (3) ◽  
pp. 477-489 ◽  
Author(s):  
Xiao-Dong Zhang ◽  
Phung N. Thai ◽  
Deborah K. Lieu ◽  
Nipavan Chiamvimonvat
Keyword(s):  
Ventricular Myocytes ◽  
Pulmonary Veins ◽  
Differential Sensitivity ◽  
Sk Channels ◽  
Sk Channel ◽  
Ventricular Cells ◽  
Intracellular Ca ◽  
Life Threatening ◽  
Health And Disease ◽  
Small Conductance

AbstractSmall-conductance Ca2+-activated K+ (SK, KCa2) channels are encoded by KCNN genes, including KCNN1, 2, and 3. The channels play critical roles in the regulation of cardiac excitability and are gated solely by beat-to-beat changes in intracellular Ca2+. The family of SK channels consists of three members with differential sensitivity to apamin. All three isoforms are expressed in human hearts. Studies over the past two decades have provided evidence to substantiate the pivotal roles of SK channels, not only in healthy heart but also with diseases including atrial fibrillation (AF), ventricular arrhythmia, and heart failure (HF). SK channels are prominently expressed in atrial myocytes and pacemaking cells, compared to ventricular cells. However, the channels are significantly upregulated in ventricular myocytes in HF and pulmonary veins in AF models. Interests in cardiac SK channels are further fueled by recent studies suggesting the possible roles of SK channels in human AF. Therefore, SK channel may represent a novel therapeutic target for atrial arrhythmias. Furthermore, SK channel function is significantly altered by human calmodulin (CaM) mutations, linked to life-threatening arrhythmia syndromes. The current review will summarize recent progress in our understanding of cardiac SK channels and the roles of SK channels in the heart in health and disease.

Safety and Efficacy of Argatroban in the Management of Heparin-Induced Thrombocytopenia

2011 ◽  
Vol 4 ◽  
pp. CMBD.S5118 ◽  
Author(s):  
Bernd Saugel ◽  
Roland M. Schmid ◽  
Wolfgang Huber
Keyword(s):  
Arterial Thrombosis ◽  
Pharmacokinetic Profile ◽  
The United States ◽  
Heparin Therapy ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Heparin Induced Thrombocytopenia ◽  
Safety And Efficacy ◽  
Increased Risk ◽  
Life Threatening

Heparin-induced thrombocytopenia (HIT) is a life-threatening adverse reaction to heparin therapy that is characterized by thrombocytopenia and an increased risk of venous and arterial thrombosis. According to guidelines, in patients with strongly suspected or confirmed HIT all sources of heparin have to be discontinued and an alternative, nonheparin anticoagulant for HIT treatment must immediately be started. For both the prophylaxis of thrombembolic events in HIT and the treatment of HIT with thrombosis the direct thrombin inhibitor argatroban is approved in the United States. The objective of this review is to describe the mechanism of action and the pharmacokinetic profile of argatroban, to characterize argatroban regarding its safety and therapeutic efficacy and to discuss its place in therapy in HIT.

Sign in / Sign up

Export Citation Format

Share Document