Management and outcome of Ebstein's anomaly in children

Abstract Objectives To assess clinical presentation, treatment, and outcome of children with Ebstein's anomaly. Background Data on long-term outcome of children with Ebstein's anomaly are scarce. Methods Retrospective analysis of all children with Ebstein's anomaly treated between February, 1979 and January, 2009 in a single tertiary institution. Primary outcomes included patient survival and need for intervention, either cardiac surgery or catheter intervention. Results A total of 42 patients were diagnosed with Ebstein's anomaly at a median age of 5 days ranging from 1 day to 11.7 years. Symptoms included cyanosis, heart murmur, and/or dyspnoea. Associated cardiac anomalies occurred in 90% of the patients. Average follow-up was 9.5 plus or minus 7.0 years. The overall mortality rate was 14%. Of the six patients, three died postnatally before treatment. Cardiac surgery and/or catheter-guided interventions were required in 33 patients (79%). Cardiac surgery was performed in 21 (50%) patients at a median age of 9.1 years (range 0.1-16.5 years), including biventricular repair in 13 (62%), one-and-a-half chamber repair in seven (33%), and a staged single-ventricle repair in one. Peri-operative mortality was 4%. Catheter-guided interventions consisted of device closure of an atrial septal defect in three cases and radiofrequency ablation of accessory pathways in nine patients. The estimated 10-year survival was 85.3 plus or minus 5.6%. Conclusion In children, Ebstein's anomaly is usually diagnosed in the first year of age. Even though children with Ebstein's anomaly often require an intervention, their peri-operative mortality is low and long-term survival is good. Symptomatic newborns requiring an intervention may have a worse outcom

Sinus node disease and arrhythmias in the long-term follow-up of former professional cyclists

Aims Significant brady- and tachyarrhythmias may occur in active endurance athletes. It is controversial whether these arrhythmias do persist after cessation of competitive endurance training. Methods and results Among all 134 former Swiss professional cyclists [hereafter, former athletes (FAs)] participating at least once in the professional bicycle race Tour de Suisse in 1955-1975, 62 (46%) were recruited for the study. The control group consisted of 62 male golfers matched for age, weight, hypertension, and cardiac medication. All participants were screened with history, clinical and echocardiographic examination, ECG, and 24 h ECG. The time for the last bicycle race of FAs was 38 ± 6 years. The mean age at examination was 66 ± 6 years in controls and 66 ± 7 years in FAs (P = 0.47). The percentage of study participants with >4 h current cardiovascular training per week was identical. QRS duration (102 ± 20 vs. 95 ± 13 ms, P = 0.03) and corrected QTc interval (416 ± 27 vs. 404 ± 18, P = 0.004) were longer in FAs. There was no significant difference in the number of isolated atrial or ventricular premature complexes, or supraventricular tachycardias in the 24 h ECG; however, ventricular tachycardias tended to occur more often in FAs than in controls (15 vs. 3%, P = 0.05). The average heart rate was lower in FAs (66 ± 9 vs. 70 ± 8 b.p.m.) (P = 0.004). Paroxysmal or persistent atrial fibrillation or flutter was reported more often in FAs (P = 0.028). Sinus node disease (SND), defined as bradycardia of 2.5 s (6 vs. 0%), was more common in FA (16%) than in controls (2%, P = 0.006). Observed survival of all FAs was not different from the expected. Conclusions Among FAs, SND occurred significantly more often compared with age-matched controls, and there is trend towards more frequent ventricular tachycardias. Further studies have to evaluate prevention of arrhythmias with extreme endurance training, the necessity of regular follow-up of heart rhythm, and management of arrhythmias in former competitive endurance athlete

The Relevance of Complementary and Integrative Medicine in the COVID-19 Pandemic: A Qualitative Review of the Literature

Background: During the COVID-19 pandemic people are facing risks of adverse health effects due to the restrictions implemented such as quarantine measures, reduced social contact, and self-isolation. In this qualitative review, we collected data on potential preventive and therapeutic health benefits of Complementary and Integrative Medicine (CIM) that might be useful during the COVID-19 pandemic. We have reviewed the scientific literature to summarize CIM practices that could be beneficial for improving physical and mental health and well-being of the population under the current pandemic circumstances. It must be noted that this review is not SARS-CoV-2 specific and we explicitly do not intend to make any SARS-CoV-2 specific health claims in this article. Methods and Findings: A qualitative, non-systematic literature review was conducted in Medline to identify literature describing preventive and therapeutic CIM approaches for strengthening mental and physical health. For a variety of CIM approaches clinical evidence was identified, indicating beneficial effects. CIM approaches include specific dietary measures and selected micronutrients, physical activity, techniques from Mind-Body Medicine, single botanicals or botanical compounds, and spending time in nature among others. The effects of CIM measures on conditions like obesity and hypertension are of special relevance here, as these conditions are considered as risk factors for a severe course of COVID-19. Moreover, a possibly direct effect of CIM approaches on immune functions and clinical parameters in respiratory tract infections, such as influenza, were identified. The findings of this review could be helpful for clinicians, patients, and the general population during the current pandemic when discussing and/or considering CIM options. Conclusions: CIM offers a variety of preventive and therapeutic options for strengthening physical and mental resilience, which could also be useful in the current COVID-19 pandemic. The evidence of CIM approaches with a potential benefit in the COVID-19 pandemic in different areas is worth to be analyzed. While this qualitative review has several obvious limitations, it might serve as useful starting point for further research on this topic

Soluble B-cell maturation antigen in lacrimal fluid as a potential biomarker and mediator of keratopathy in multiple myeloma

Belantamab mafodotin (belantamab) is a first-in-class anti-BCMA antibody-drug conjugate approved for the treatment of triple-class refractory multiple myeloma. It provides a unique therapeutic option for patients ineligible for CAR-T and bispecific antibody therapy, and/or patients progressing on anti-CD38 treatment where CAR-T and bispecifics might be kept in reserve. Wider use of the drug can be challenged by its distinct ocular side effect profile, including corneal microcysts and keratopathy. While dose reduction has been the most effective way to reduce these toxicities, the underlying mechanism of this BCMA off-target effect remains to be characterized. In this study, we provide the first evidence for soluble BCMA (sBCMA) in lacrimal fluid and report on its correlation with tumor burden in myeloma patients. We confirm that corneal cells do not express BCMA, and show that sBCMA-belantamab complexes may rather be internalized by corneal epithelial cells through receptor-ligand independent pinocytosis. Using an hTcEpi corneal cell-line model, we show that the pinocytosis inhibitor EIPA significantly reduces belantamab-specific cell killing. As a proof of concept, we provide detailed patient profiles demonstrating that, after belantamab-induced cell killing, sBCMA is released into circulation, followed by a delayed increase of sBCMA in the tear fluid and subsequent onset of keratopathy. Based on the proposed mechanism, pinocytosis-induced keratopathy can be prevented by lowering the entry of sBCMA into the lacrimal fluid. Future therapeutic concepts may therefore consist of belantamab-free debulking therapy prior to belantamab consolidation and/or concomitant use of gamma-secretase inhibition as currently evaluated for belantamab and nirogacestat in ongoing studies

Membrane-mediated interactions

Interactions mediated by the cell membrane between inclusions, such as membrane proteins or antimicrobial peptides, play important roles in their biological activity. They also constitute a fascinating challenge for physicists, since they test the boundaries of our understanding of self-assembled lipid membranes, which are remarkable examples of two-dimensional complex fluids. Inclusions can couple to various degrees of freedom of the membrane, resulting in different types of interactions. In this chapter, we review the membrane-mediated interactions that arise from direct constraints imposed by inclusions on the shape of the membrane. These effects are generic and do not depend on specific chemical interactions. Hence, they can be studied using coarse-grained soft matter descriptions. We deal with long-range membrane-mediated interactions due to the constraints imposed by inclusions on membrane curvature and on its fluctuations. We also discuss the shorter-range interactions that arise from the constraints on membrane thickness imposed by inclusions presenting a hydrophobic mismatch with the membrane.Comment: 38 pages, 10 figures, pre-submission version. In: Bassereau P., Sens P. (eds) Physics of Biological Membranes. Springer, Cha

Air-sea fluxes of greenhouse gases and oxygen in the northern Benguela Current region during upwelling events

Ground-based atmospheric observations of CO2, delta(O-2/N-2), N2O, and CH4 were used to make estimates of the air-sea fluxes of these species from the Luderitz and Walvis Bay upwelling cells in the northern Benguela region, during upwelling events. Average flux densities (+/- 1 sigma) were 0:65 +/- 0:4 mu mol m(-2) s(-1) for CO2, -5.1 +/- 2:5 mu mol m(-2) s(-1) for O-2 (as APO), 0:61 +/- 0:5 nmol m(-2) s(-1) for N2O, and 4:8 +/- 6:3 nmol m(-2)s(-1) for CH4. A comparison of our top-down (i.e., inferred from atmospheric anomalies) flux estimates with shipboard-based measurements showed that the two approaches agreed within +/- 55% on average, though the degree of agreement varied by species and was best for CO2. Since the top-down method overestimated the flux density relative to the shipboard-based approach for all species, we also present flux density estimates that have been tuned to best match the shipboard fluxes. During the study, upwelling events were sources of CO2, N2O, and CH4 to the atmosphere. N2O fluxes were fairly low, in accordance with previous work suggesting that the evasion of this gas from the Benguela is smaller than for other eastern boundary upwelling systems (EBUS). Conversely, CH4 release was quite high for the marine environment, a result that supports studies that indicated a large sedimentary source of CH4 in the Walvis Bay area. These results demonstrate the suitability of atmospheric time series for characterizing the temporal variability of upwelling events and their influence on the overall marine greenhouse gas (GHG) emissions from the northern Benguela region.Peer reviewe

Long-term follow-up after thoracic radiotherapy: symptomatic heart disease is an ominous digne

Background: Thoracic radiotherapy (RT), especially with past technology, may affect the heart, but rarely leads to symptoms. In patients with symptomatic heart disease after RT, outcome seems to be dismal. Methods: In this observational descriptive study, clinical characteristics, findings of ECG, echocardiography, cardiac interventions and follow-up were analysed in patients with prior RT and symptomatic heart disease. The patients were identified in the echocardiography database during a ten year period. Results: There were 25 patients who had thoracic RT at a median age of 35 years (range: 9–59) for lymphoma (12 patients), breast cancer (9) or other cancer (4). At least likely inclusion of the heart in the target volume of previous RT was present in of 16 of 20 patients with detailed information on RT. Last follow-up was 24 years (range: 5–57) after RT at a median age of 56 years (range: 30–84). Symptoms (≥1 per patient) included: dyspnea (21 patients), angina (12) and/or heart failure (10). Three patients had prior myocardial infarction. The following disease was found: moderate valvular disease in 19 patients (76%), coronary artery disease in 12 (48%), abnormal ECG in 18 (72%), relevant conduction system disease in 9 (36%), restriction / constriction in 7 (28%), and pericardial effusion in 4 (16%). Cardiac surgery was necessary in 12 patients (death in 2 patients), percutaneous coronary interventions in 5 and pacemaker implantation in 3. Endocarditis occurred in 2 patients. During follow-up (21 ± 8 months), death occurred in 6 patients (24%) and was due to heart disease in 5 of them. Conclusions: If symptomatic heart disease develops in the long-term follow-up after RT, complex disease of valves, coronary arteries, conduction system, myocardium and pericardium is frequently observed. Cardiac interventions are often necessary; and heart disdisease may be a common cause of death in these patients. Careful assessment and evaluation of treatment options are needed in this patient group