Longevity is highly variable among animal species, and has coevolved with other of life-history traits, like body size and rates of reproduction. Telomeres, through their erosion over time, are one of the cell mechanisms that produce senescence at the cell level, and might even have an influence on the rate of ageing in whole organisms. However, uneroded telomeres are also risk factors of cell immortalization. The associations of telomere lengths, their rate of change, and life-history traits independent of body size are largely underexplored for birds. To test associations of life-history traits and telomere dynamics, we conducted a phylogenetic meta-analysis using studies of 53 species of birds. We restricted analyses to studies that applied the telomere restriction fragment length (TRF) method, and examined relationships between mean telomere length at the chick (Chick TL) and adult (Adult TL) stages, the mean rate of change in telomere length during life (TROC), and life-history traits. We examined 3 principal components of 12 life-history variables that represented: body size (PC1), the slow-fast continuum of pace-of-life (PC2) and post-fledging parental care (PC3). Phylogeny had at best a small-to-medium influence on Adult and Chick TL (r² = 0.190 and 0.138, respectively), but a substantial influence on TROC (r² = 0.688). Phylogeny strongly influenced life histories: PC1 (r² = 0.828), PC2 (0.838), and PC3 (0.613). Adult TL and Chick TL were poorly associated with the life-history variables. TROC, however, was negatively and moderate-to-strongly associated with PC2 (unadjusted r = -0.340; with phylogenetic correction, r = -0.490). Independent of body size, long-lived species with smaller clutches and slower embryonic rate of growth may exhibited less change in telomere length over their lifetimes. We suggest that telomere lengths may have diverged even among closely avian related species, yet telomere dynamics are strongly linked to the pace of life.
Cytokine Filter Application in COVID-19 Patients; Island of Hope for Crash and Burn Patients or Future Solution for All Septic Acute Respiratory Distress Syndrome (ARDS) PatientsAli Ghodsizad MD, PhD, FACC, FETCS, FACSThe COVID-19 pandemic crisis certainly has challenged the scientific community as well as entire world. While incidence numbers have decreased following expedited vaccination and precautions, still some patients present with COVID 19 related pneumonia and ARDS requiring Veno-Venous Extracorporeal Membrane Oxygenation (VV ECMO) support to survive.In COVID-19 patients a cytokine release syndrome concomitant with ARDS can lead to overwhelming clinical scenario. Geraci and colleagues report on their single center feasibility study looking at application of the CytosorbTM hemadsorption device which was used as a parallel circuit within the VV ECMO circuit.The authors give evidence for safety and feasibility of the CytosorbTM hemadsorption device use in 10 patients with COVID-19 related ARDS in combination with VV ECMO. They show a reduction of inflammatory markers and cytokines following hemadsorption treatment. The cytokine storm can cause a critical clinical picture of septic shock. Only under high vasopressor and inotropic support end organ perfusion can be maintained. The required invasive pressure ventilation with high PEEP and peak pressure can decrease the intrathoracic venous return further and contributes more to the shock physiology (1). We have to look at inspiring results from current single center experience carefully understanding the evolving nature of COVID-19 related ARDS. Other groups have used plasmapheresis and CVVH modifications in COVID-19 cases. Dominik et al have shown a significant benefit only using hemadsorption comparing to other used protocols (2).We have shown successful application of somatic stem cells in COVID-19 patients on VV ECMO at our center. We could observe a reduction of inflammatory markers following somatic stem cell application (3). COVID 19 ARDS patients who required VV ECMO support, underwent a Pulmonary Artery (PA)-catheter placement and allogenic human stem cell injection into the PA using the PA-catheter as part of our expanded access protocol (3,4).Brouwer and colleagues, another group working with hemadsorption, have actually shown reduced survival in patients undergoing hemadsorption therapy (5). Geraci and colleagues describe their overall VV ECMO survival for COVID 19 related respiratory failure to be > 90%. Others including our center have experienced a much lower survival in that patient population. So patient selection clearly is a key point. The results presented by Geraci and colleagues have to be taken as a pioneering step, which can help in ARDS and septic clinical scenarios with different pathology in future.
Aims：This study aimed to investigate the safety, feasibility and availability of perimembranous ventricular septal defect (PmVSD) closure via a left parasternal ultra-minimal trans intercostal incision in children. Methods and results：From January 2015 to January 2019, 131 children with restrictive PmVSDs were enrolled in this study and successfully done in 126 patients (96.18%). PmVSDs were occluded via an ultra-minimal trans intercostal incision (≤1 cm), and the entire occlusive process was guided and monitored by TEE. A pericardium hanging technique was employed without sternal incision. PmVSDs were closed through a short delivery sheath assembled using a concentric occluder device. All patients were followed up for a perid ranging from18 months to 24 months. Thirteen patients with PmVSD had aneurysm of membranous septum (AMS). Multistream (more than or equal to 2) PmVSDs with AMS were found in eleven cases. After the operation, mild residual shunt beside the amplatzer occluder in one patient was found and had self-healing result during the 5-month follow-up period. Five patients transferred to ventricular septal defect repair operation under direct visualization with a cardiopulmonary bypass. One reason was ventricular fibrillation when guide wire passed the PmVSD, another was device dislocation, and others were the guide wire cannot pass through the PmVSD. Conclusions：PmVSDs closure using a concentric occluder via a left parasternal ultra-minimal trans intercostal incision under TEE guidance is feasible, safe, and effective in children. This approach can be considered as an alternative treatment to open-heart surgery for restrictive PmVSDs.
The construction of morphological character matrices is central to paleontological systematic study, which extracts paleontological information from fossils. Although the word information has been repeatedly mentioned in a wide array of paleontological systematic studies, its meaning has rarely been clarified and there has not been a standard to measure paleontological information due to the incompleteness of fossils, difficulty of recognizing homologous and homoplastic structures, etc. Here, based on information theory, we show the deep connections between paleontological systematic study and communication system engineering. It is information, the decrease of uncertainty, in morphological characters that distinguishes operational taxonomic units (OTUs) and reconstructs evolutionary history. We propose that concepts in communication system engineering such as source coding and channel coding correspond in paleontological studies to the construction of diagnostic features and the entire character matrices, which should be distinguished as how typical communication systems are engineered because these two steps serve dual purposes. With character matrices from six different vertebrate groups, we analyzed their information properties including source entropy, mutual information, and channel capacity. Estimation of channel capacity shows upper limits of all matrices in transmitting paleontological information, indicating that, due to the presence of noise, too many characters not only increase the burden in character scoring, but also may decrease quality of matrices. Information entropy, which measure how informative a variable is, of each character is tested as a weighting criterion in parsimony-based systematic studies, the results show high consistence with existing knowledge with both good resolution and interpretability.
Background Randomised trials show high long-term patency for no-touch saphenous vein grafts in coronary artery bypass grafting. The patency rate in off-pump coronary bypass surgery for these grafts has not been investigated. Our centre participated in the CORONARY randomized trial, NCT00463294. This is a sub-study aimed to assess the patency of no-touch saphenous veins in on- versus off-pump coronary bypass surgery at five-year follow-up. Methods Fifty-six patients were included. Forty of 49 patients, alive at five years, participated in this follow-up. There were 21 and 19 patients in the on- and off-pump groups respectively. No-touch saphenous veins were used to bypass all targets and in some cases the left anterior descending artery. Graft patency according to distal anastomosis was evaluated with computed tomography angiography. Results The five-year patency rate was 123/139 (88.5%). The patency for the no-touch vein grafts was 57/64 (89.1%) in the on-pump vs 37/45 (82.2%) in the off-pump group. All left internal thoracic arteries except for one, 29/30 (96.6%), were patent. All vein grafts used to bypass the left anterior descending and the diagonal arteries were patent 32/32. The lowest patency rate for the saphenous veins was to the right coronary territory, particularly in off-pump surgery (80.0% vs 62.5% for the on- respective off-pump groups). Conclusions Comparable five-year patency for the no-touch saphenous veins and the left internal thoracic arteries to the left anterior descending territory in both on- and off-pump coronary artery bypass grafting. Graft patency in off-pump CABG is lower to the right coronary artery.
A retrospective analysis of recurrent pediatric ependymoma reveals extremely poor survival ind ineffectiveness of current treatments across central nervous locations and molecular subgroups. Tryggve Lundar MD, PhD1,2, Bernt Johan Due-Tønnessen MD,PhD1Radec Fric MD,PhD1Department of Neurosurgery, Oslo University Hospital1and University of Oslo2Correponding author:Tryggve LundarDepartment of NeurosurgeryOslo University HospitalPostboks 4950 Nydalen, Oslo, NorwayEmail: firstname.lastname@example.orgTotal word count: 474Short running title: GTR can improve outcome after relapse of pediatric ependymomaKey words: Pediatric ependymoma, relapse, repeat surgical resection (GTR)Number of tables: 0Number of figures: 0Letter to the EditorPediatr Blood CancerDear Editor,RE: Ritzmann TA, Rogers HA, Paine SML, Storer LCD, Jacques TS, Chapman RJ, Ellison D, Donson AM, Foreman NK, Grundy RG.A retrospective analysis of recurrent pediatric ependymoma reveals extremely poor survival ind ineffectiveness of current treatments across central nervous locations and molecular subgroups.Pediatr Blood Cancer 2020;67:e28426https://doi.org/10.1002/pbc.28426Congratulations to the authors with their detailed analysis of further management and outcome in pediatric patients who experience recurrence within a few years after initial treatment for ependymomas.Initial treatment for posterior fossa ependymomas (PFE) is maximal surgical resection (Gross total resection-GTR; if possible) followed by local radiotherapy or chemotherapy in small children. For supratentorial ependymomas (STE) GTR is also recommended (if possible) with or without postoperative radiotherapy.The management at relapses is, however, without consensus. The authors confirm the grave prognosis for these children. In the beginning of the discussion they state: Although primary surgery and irradiation reduced relapse risk variability in different intracranial locations, once a patient recurred these interventions gave, at best, short-term benefits, confirming the need for better therapies.This of course true – better therapies are urgently needed. They point to the lack of consensus regarding treatment at relapse, but recent guidelines have recommended the use of reirradiation and further surgery. In the conclusion they underline that recurrent pediatric ependymoma is highly aggressive with extremely poor outcome.This negative statement, is to some extent, in conflict with the results given under 3.5.2. At relapse: GTR at first relapse was associated with sustained improved EFS (25% vs 0% 10-year survival).This statement is in accord with Vinchon et al1 : Total resection is the only curative treatment for RIE (recurrent intracranial ependymoma) and is often possible, especially when the initial resection was total.How often GTR is within reach at local relapes may be a difficult matter. We have, however, observed several patients who underwent GTR after recurrence, and are tumor-free today after many years of further follow-up(up to 27 years) without any additional treatment2. We recognize that these patients are few compared to the majority of pediatric ependymoma patients who do not grow-up to be well functioning adults. It is, however, important for these small patients and their caretakers to have a hope for cure even after relapse. The role of GTR if possible may be under-communicated.Kind regardsTryggve LundarBernt Johan Due-TønnessenRadek Fric
Background: Data on influenza incidence during pregnancy in China are limited. Methods: From October 2015–September 2018, we conducted active surveillance for acute respiratory illness (ARI) among women during pregnancy. Nurses conducted twice weekly phone and text message follow-up upon enrollment until delivery to identify new episodes of ARI. Nasal and throat swabs were collected ≤10 days from illness onset to detect influenza. Results: In total, we enrolled 18,724 pregnant women median aged 28yo, 37% in first trimester, 48% in second trimester and 15% in third trimester, with 7 self-reported vaccination during pregnancy. In the 18-week epidemic period during October 2015–September 2016, influenza incidence was 0.7/100 person-months (95% CI:0.5–0.9). In the 29-week epidemic during October 2016–September 2017, influenza incidence was 1.0/100 person-months (95% CI:0.8–1.2). In the 11-week epidemic period during October 2017–September 2018, influenza incidence was 2.1/100 person-months (95% CI:1.9–2.4). Influenza incidence was similar by trimester. More than half of the total influenza illnesses had no elevated temperature and cough. Most influenza-associated ARIs were mild, and <5.1% required hospitalization. Conclusions: Influenza illness in all trimesters of pregnancy was common. These data may help inform decisions regarding the use of influenza vaccine to prevent influenza during pregnancy.
Cardiac Transplantation as Surgical Treatment for Cardiac Sarcoidosis Ali Ghodsizad MD, PhD, FACC, FETCS, FACSSarcoidosis is a complex disease with different clinical presentations that can involve multiple organs (1). The lung is typically the most common organ involved, multiple organ involvements with pulmonary and cardiac sarcoidosis account for most of the morbidity and mortality observed with this disease (1). Cardiac sarcoidosis presents as a progressive infiltrative cardiomyopathy that can lead to heart failure, arrhythmia and death (1).Here McGoldrick and colleagues report on their database study with data from Organ Procurement and Transplantation Network (OPTN) involving 289 cardiac sarcoidosis patients with end stage restrictive cardiomyopathy, who needed cardiac transplantation and compared them with all non-sarcoid patients undergoing cardiac transplantation for restrictive cardiomyopathy and end stage heart failure of other causes between Jan 1999 to March 2020 (n=41447).Patients with cardiac sarcoidosis had a comparable survival to non-sarcoid patients at 1 and 5 years and a significantly longer survival at up to 10 years.Patients with cardiac sarcoidosis had an increased chance to die from aspergillus infections at 1 year. Jackson et al showed in their multicenter trial comparable survival, rate of graft failure, and incidence of treated rejection at 1 year when compared to matched non-sarcoid patients. Sarcoid patients after heart transplantation were less likely to be hospitalized for infection in their study at 1 year (2). Liu et al performed a similar UNOS data base study showing that cardiac sarcoidosis heart transplant recipients were an older population with less underlying co-morbidities with a lower overall mortality (3).The diagnosis of cardiac sarcoidosis in patients who undergo left ventricular assist device implantation can be confirmed by histological examination of myocardium at the time of ventricular assist device insertion, but unclear is the predictive value (4,5).McGoldrick and colleagues excluded patients who required multiorgan transplantation in all 3 groups and we have to consider that multiorgan recipients belong to the sickest subpopulation.McGoldrick et al and other groups confirm the role of cardiac transplantation as a viable option for patients with cardiac sarcoidosis. Considering the increasing number of the cardiac transplantation for sarcoidosis in recent years, the 10 years survival data may have to be reevaluated with more follow up time in future.
HIT is a massive thrombotic storm. The incidence of thrombotic complications is up to 50%, and the mortality rate is up to 20% in untreated cases. The patient’s presentation was subtle, with mild thrombocytopenia. The consequences would have been catastrophic if cardioversion was done using the standard guidelines.
SUCCESSFUL USE OF CRUSHED FORMULATION OF DABRAFENIB AND TRAMETINIB IN A PEDIATRIC GLIONEURAL TUMORTania Mamdouhi1, Anshul Vagrecha2, Alan A. Johnson1,3, Carolyn Fein Levy1,2, Mark Atlas 1,2, Julie I. Krystal 1,2 1 Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY2 Department of Pediatrics, Division of Hematology/Oncology and Cellular Therapy, Cohen Children’s Medical Center, New Hyde Park, NY3 Department of Radiology, Division of Neuroradiology, Long Island Jewish Medical Center, New Hyde Park, NYCorresponding Author : Julie Krystal. Cohen Children’s Medical Center, 269- 01 76th Avenue, Suite 255, New Hyde Park, NY 11040. Jkrystal12@northwell.edu. Phone 718-470-3460. Fax 718-343-4642.Tables: 0Figures: 1Supporting Information Files : 0Short running title: Use of crushed formulation of dabrafenib and trametinibKeywords : Dabrafenib, Trametinib, BRAF, crushedData Availability: The data that support the findings of this study are available from the corresponding author upon reasonable request.
Purpose: Extracorporeal membrane oxygenation (ECMO) is a refractory treatment for acute respiratory distress syndrome (ARDS) due to influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also referred to as COVID-19). We conducted this study to compare the outcomes of influenza patients treated with veno-venous-ECMO (VV-ECMO) to COVID-19 patients treated with VV-ECMO, during the first wave of COVID-19. Materials and Methods: Patients in our institution with ARDS due to COVID-19 or influenza who were placed on ECMO between August 1, 2010 and September 15, 2020 were included in this comparative, retrospective study. To improve homogeneity, only VV -ECMO patients were analyzed. The clinical characteristics and outcomes were extracted and analyzed. Results: 28 COVID-19 patients and 17 influenza patients were identified and included. ECMO survival rates were 68% (19/28) in COVID-19 patients and 94% (16/17) in influenza patients (p=0.04). 30-day survival rates after ECMO decannulation were 54% (15/28) in COVID-19 patients and 76% (13/17) in influenza patients (p=0.13). COVID-19 patients spent a longer time on ECMO compared to flu patients (21 days vs. 12 days, p=0.025), and more COVID-19 patients (26/28 vs. 2/17) were on immunomodulatory therapy prior to ECMO initiation (p<0.001). COVID-19 patients had higher rates of new infections during ECMO (50% vs. 18%, p=0.03) and bacterial pneumonia (36% vs 6%, p=0.024). Conclusions: COVID-19 patients who were treated in our institution with VV-ECMO had statistically lower ECMO survival rates than influenza patients. It is possible that COVID-19 immunomodulation therapies may increase the risk of other superimposed infections.
The authors successfully utilize the bidirectional Glenn procedure to palliate late presenting, cyanotic patients with complex congenital heart disease. Additional information regarding preoperative diagnostic testing would be helpful. There is little information regarding patient screening and selection for the procedure. The short term results are satisfactory, however, mid-term and longer follow-up data is lacking. The treatment algorithm suggested by the report might be useful in other settings.
The authors report an exceptionally rare patient with findings of a bicuspid aortic valve in conjunction with a mature cystic teratoma in a middle-aged male presenting for symptomatic chest pain. Surgical resection and valve replacement were performed, confirming the rare cardiac tumor. While certainly interesting, this case highlights the importance of maintaining a broad differential diagnosis and the appropriate work-up, treatment and considerations for such rare pathology.