Viruses are considered as one of the primary drivers for human evolution. Humans in return have also offered them an ideal habitat for their growth and evaluation. However, both, humans and viruses are diverse, astute, competitive, and avaricious in nature, which engage them in a never-ending battle. Today, the world goes to win the battle against COVID-19 for sure. However, this never ending merciless battle between viruses and humans looks like an arms race for their survival in which neither a virus wins nor a human but each battle provides them an opportunity to bounce back for the next.

A document by Maryam Azimzadeh Irani. Click on the document to view its contents.

The SARS-CoV-2 infection has been considered a global pandemic due to its widespread transmission and high rate of fatality. As of April 11, 2020, globally, there are 1.76 million confirmed cases of COVID-19, of which 108,281 people succumbed to the disease. In the absence of therapeutic intervention and a possible vaccine candidate, the spread of the disease and associated fatalities are on the rise. The epidemiological data indicate age and country-specific bias in the spread and severity of COVID-19. In this review, we discussed the recent update on the pathogenesis of SARS-CoV-2 among men and women, including children. Further, we also discuss the role of the cellular receptors and co-receptors used by the virus to enter host cells in the virus pathogenesis on differential infection among men and women. Further, highlighted the co-morbidity of COVID-19 with cardio-metabolic disease, and the potential treatments to control SARS-CoV-2 infection. Finally, we summarize the prospective treatment options that have been evaluated or are in the pipeline at different stages of clinical trials to fight against COVID-19.

Oxidized low-density lipoproteins (oxLDL) and oxysterols play a key role in the endothelial dysfunction and atherosclerosis development. Loss of vascular endothelium integrity impacts vasomotion, cell growth, adhesiveness and barrier functions. While for some of these disturbances we can give a reasonable explanation from a mechanistic point of view, for many others the involved molecular players are unknown. Caveolae, specific plasma membrane domains, have recently emerged as targets and mediators of oxLDL-induced endothelial cell dysfunction. The current knowledge on oxLDL/caveolae interplay and the associated signal transduction pathways are here reviewed and discussed in light of the possible cross-talk between transducers (from receptors to membrane cholesterol) and/or effectors. A better understanding of how oxLDL interact with endothelial cells (EC) and, in turn, modulate metabolic/signaling pathways in EC is crucial to define their role in atherogenesis and find new targets of intervention.

We read with great interest the recent study by Rogers, et al. describing lesion formation with continuous versus intermittent radiofrequency ablation.1 The authors applied 50 (ex-vivo) or 10 (in-vivo) watts with either intermittent (15-seconds x4, 30-seconds x2, or 60-seconds x1) or continuous (1, 2, 3, or 5 minutes) radiofrequency applications and examined lesion size with each strategy. Continuous lesions resulted in significantly larger lesion size with possibly increased risk of steam pops at high power. In the ex-vivo model, they saw rapid lesion formation in the first minute of ablation with substantial drop-off in expansion of lesion size over time especially after 3 minutes (down to 0.35mm/min at 5 minutes), and suggest that there is only minimal incremental benefit of prolonging ablation lesion duration beyond 3 minutes in normal tissue.They have, however, appropriately recognized the limitation of their model which lacks significant fibrosis, limiting the generalizability of their findings to ablation in patients with scar. It is important to recognize that lesion formation in scar-related ventricular tachycardia (VT) is likely to differ dramatically compared to normal myocardial tissue. Barkargan, et al. have shown in an in-vivo porcine model of anterior myocardial infarction that lesion formation in normal versus scar tissue can be substantially different.2Specifically, ablation lesions in scar tissue were histologically quite heterogeneous, and connective tissue tended to be more resistant to thermal injury than normal myocardium.We have seen many cases where after identifying critical VT circuit components with activation and entrainment mapping, VT slowing and termination could only be achieved very late (4-5 minutes) into radiofrequency application, suggesting continued lesion expansion due to delayed effect of conductive heating in scar tissue can persist well beyond 3 minutes. Historical data from Nath, et al. have demonstrated that tissue temperature of >50°C must be reached in order to achieve nonreversible cellular damage.3 In the setting of dense scar, as in patients with healed myocardial infarction or dense basal septal scar in nonischemic cardiomyopathy, dynamics of tissue heating and lesion formation are likely quite different than in normal tissue. Especially in intramural substrates which are “protected” by dense subendocardial (or subepicardial if ablating from the epicardium) scar, ablation with very long (>3 minute) lesions may have a more pronounced effect than in normal tissue. While in our experience, steam pops seem to occur less frequently when ablating in dense scar- even with long, high power lesions, close monitoring of ablation parameters including catheter tip temperature and impedance remain necessary during ablation to assure continued safety to avoid char formation and steam pops.We enthusiastically applaud the authors for their valuable contribution to the literature. While chronic cardiomyopathy models are technically difficult to create and costly to maintain, additional studies examining lesion formation in dense scar would be extremely helpful to delineate optimal ablation strategies in patient with cardiomyopathy and difficult VT substrates. Our clinical experience with late VT termination and prevention of inducibility after 4-5 minute radiofrequency ablation lesions in areas of marked fibrosis would support such additional study.References:1. Rogers AJ, Borne RT, Ho G, Sauer WH, Wang PJ, Narayan SM, Zheng L, Nguyen DT. Continuous Ablation Improves Lesion Maturation Compared with Intermittent Ablation Strategies. J Cardiovasc Electrophysiol 2020.2. Barkagan M, Leshem E, Shapira-Daniels A, Sroubek J, Buxton AE, Saffitz JE, Anter E. Histopathological Characterization of Radiofrequency Ablation in Ventricular Scar Tissue. JACC Clin Electrophysiol 2019;5:920-931.3. Nath S, DiMarco JP, Gallop RG, McRury ID, Haines DE. Effects of dispersive electrode position and surface area on electrical parameters and temperature during radiofrequency catheter ablation. Am J Cardiol 1996;77:765-767.

ABSTRACT Background: Data regarding the use of high-power short-duration (HPSD) radiofrequency (RF) in combination with half-normal saline irrigation for catheter irrigation is limited. Objectives: This study investigated the safety and efficacy of using HPSD RF ablation in combination with half-normal saline irrigation for the treatment of AF. Methods: One hundred consecutive patients with AF underwent RF ablation using HPSD combined with half-normal saline for catheter irrigation. In addition, the following ablation strategies were used: 1 mm tags for the display of ablation lesions on the mapping system, high-frequency jet ventilation (HFJV), low contact force, pacing after ablation to verify areas of noncapture, atrial/ventricular pacing at 500 to 700 ms to aid in catheter stability, use of two skin electrodes to reduce impedance, and post-ablation adenosine infusion. Power was started at 40-45 W and was modulated manually based on impedance changes. Results: The average age of patients was 65.2 years and 70% were male. Forty-seven percent had paroxysmal AF and the average CHA2DS2-VASc score was 2.1±1.6. The average power and lesion duration were 38.1 ± 3.3 W and 8.1 ± 2.3 seconds, respectively. During a median follow-up period of 321 + 139 days, 89% of the patients remained free from any atrial arrhythmias after a single RF ablation procedure. No procedure-related death, stroke, pericardial effusion, or atrioesophageal fistula occurred during follow-up. Conclusions: Catheter ablation using HPSD RF lesions in combination with half-normal saline irrigation and is safe and effective, and results in high rate of freedom from AF.

Introduction: Brugada syndrome is associated with ventricular arrhythmia leading to sudden cardiac death. Risk stratification is challenging, as major arrhythmic events (MAE) are rare. We assessed the utility of drug challenge testing in Brugada syndrome by a systematic review and meta-analysis. Methods and results: We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2019. Included studies compared the incidence of MAE between spontaneous and drug challenge induced Type-1. Data were combined using the random-effects, generic inverse variance method, to calculate pooled incidence and odds ratio (OR). Mixed-effects Poisson regression was used to calculated incidence rate ratio (IRR). Eighteen studies from 2006 to 2018 were included (4,099 patients, mean follow-up 4.5 years). Pooled annual incidences of MAE in spontaneous, drug challenge induced (regardless of symptoms), asymptomatic drug challenge induced, and symptomatic drug challenge induced Type-1 were 23.8 (95% confidence interval [CI]: 19.8-27.8), 6.5 (95% CI: 3.9-9.1), 2.1 (95% CI: -0.3-4.4), and 19.6 (95% CI: 9.9-29.3) per 1,000 person-years respectively. The incidence of MAE between symptomatic drug challenge induced and asymptomatic spontaneous Type-1 was not statistically different (IRR=1.0, 95%CI: 0.6-1.7). The presence of ventricular tachyarrhythmia during drug challenge testing was a predictor of MAE (OR=3.73, 95% CI: 1.77-7.86, p=0.001). Conclusions: The incidence of MAE in drug challenge induced Type-1 in asymptomatic patients is low. The incidence of MAE between symptomatic drug challenge induced and asymptomatic spontaneous Type-1 was similar. Ventricular tachyarrhythmia during drug challenge testing could be a useful risk marker for MAE in Brugada syndrome.

Leadless pacemakers have an accepted role with demonstrable benefit in adults. In contrast, implant and follow-up experience in pediatric patients is quite limited. We present our implant experience in a 4-year-old for treatment of high-grade AV block. Implant considerations in small patients and follow-up assessment of the vessel used for implantation are discussed.

Despite extreme and undeniable progress in the concept of implantable cardioverter defibrillator (ICD) therapy over the last 40 years, the endocardial lead is still the weakest link of the system. Many efforts have been taken to improve the construction and consequently the durability of the lead. Not all of them were successful and some of the lead models proved to be technically imperfect, resulting in formal recalls. Similarly, patient- and procedure-related factors may strongly affect the lead reliability. The implantation of cardiac electronic devices (CIED) is considered to be a quite common vascular intervention. Also, there are strongly established opinions of best procedural manners, including the most optimal methods of vascular access during the CIED implantations.In this issue of the Journal of Cardiovascular Electrophysiology, Barbhaiya et al. present an interesting retrospective analysis of 660 patients who underwent the ICD implantations in one center from 2011-2017. The goal of the study was to determine the risk factors for premature lead failure. Four implanted leads models were assessed: Biotronik Linox, Sprint Quattro, Durata and Endotak.The main findings include:The ICD lead implantation via cephalic access in multi-lead ICD systems may be a risk factor for premature ICD lead failure (p<0.001).The overall risk of premature ICD lead failure was similar for all the analyzed lead models.Concerns regarding the durability of Biotronik Linox were discussed and the study showed its equal reliability compared to the other leads.Neither age nor gender were the risk factors for premature lead failure.An optimal vascular access for the endocardial lead implantation was investigated in many studies.1-4 So far, cephalic vein cutdown (CVC) was considered to be the method of choice, with the lowest rate of possible complications.2,4,5 Meta-analysis performed by Benz et al. (30 000 patients, more than 50 000 leads) compared CVC and subclavian puncture (SP) and demonstrated lower risk of lead failure when CVC was adopted.2 Axillary vein puncture (AP), especially when ultrasonography-guided, is a feasible technique and significantly reduces the probability of subclavian crush syndrome.6-8 Unfortunately this method is not used by many operators. EHRA survey from 2013 showed that in more than 80% of participating centers, the preferred method for venous access was either CVC or SP.9 What is worth emphasizing, in the study of Barbhaiya et al., axillary access was most often used for lead insertion – 76.8% (61-88%, dependently on the lead model). This fact may potentially explain the main study finding. It is also consistent with the interesting results of the PAIDLESS study presented in the paper of Shaikh et al.3 They showed that experienced operators preferably choose subclavian and/or axillary access (62% of implants), whereas low-volume implanters generally use cephalic vein approach (63%). High-volume operators are also less likely to experience lead failure.An important issue to discuss is the number of leads inserted via cephalic vein. The routine practice, also applied by Barbhaiya and colleagues, includes the placing of atrial and right ventricular leads via cephalic access, if possible. Inserting one or two leads is usually not a problem. There are many inventive ways for doing this, described in literature. Some operators go even further – they use cephalic vein to implant all three leads of cardiac resynchronization therapy (CRT) systems with the success rate of 87.7% - 91.7%.10,11The question of long-term reliability of the leads implanted in such a way is still open. They are tightly packed in one small vessel and possible lead - lead interaction may contribute to their failure. Especially the ICD leads, by definition more complex and sensitive, are prone to damage in these circumstances.Another possible locus minoris resistentiae is the site of cephalic vein ligation after the lead insertion. The line between an adequate and too strong suture tightening is quite narrow. The effort to stop the bleeding from the vein may cause ligation-induced lead insulation damage. Recently, Kajiyama et al. proposed a novel technique for the ligation of the cephalic vein during a two-in-one insertion of the leads.12 It reduces hemorrhaging without decreasing the lead safety.The discussion about the benefits of different vascular access should include the potential disadvantages of future lead extraction, especially in the multi-lead systems. Inserting more than one lead via cephalic vein may determine more problematic transvenous lead extraction procedure (TLE). It may also necessitate the extraction of the functioning lead because of its periprocedural damage during the TLE of the initially targeted lead.The reliability of ICD leads is certainly the most important feature. During the last decades several lead models produced by different manufacturers were recalled because of their serious technical defects. Numerous concerns and divergent literature data regarding the durability of the Linox lead were the premise for the authors to conduct the discussed study. An important observation is that all analyzed lead models, including Linox, were similar in terms of performance (p=0.769).Young and physically active patients were traditionally believed to have a higher risk of lead damage because of the intensive mechanical interaction between the lead and anatomical structures of costoclavicular space. This observation was not confirmed by the authors of the commented paper.The study has several limitations and they are all listed by the authors. The lack of multivariate risk factors analysis is the most important drawback. It could not be performed due to the low overall event rate. All interesting study findings require validation and further investigation.As the ICD lead failure is still a serious problem, the study investigating possible risk factors is always of great importance. With all the limitations, the paper presented by Barbhaiya et al. may be an important guide in dealing with the vascular access during CIED implantations. It sheds new light on the dogma of superiority of cephalic access. What is particularly important in the study outcome and what I personally find a very strong recommendation – is the conclusion that the multiple lead systems should be avoided, if not indicated, especially when combined with cephalic venous access. One possible solution is to use cephalic vein for one lead only. Prospective randomized studies directly comparing axillary and cephalic access would be highly desirable in order to come closer to the idea of the best vascular approach for the endocardial lead implantation.1. Knight BP, Curlett K, Oral H, Pelosi F, Morady F, Strickberger SA. Clinical predictors of successful cephalic vein access for implantation of endocardial leads. J Interv Card Electrophysiol.2002;7(2):177-180.2. Benz AP, Vamos M, Erath JW, Hohnloser SH. Cephalic vs. subclavian lead implantation in cardiac implantable electronic devices: a systematic review and meta-analysis. Europace.2019;21(1):121-129.3. Shaikh ZA, Chung JA, Kersten DJ, et al. Differences in Approaches and Outcomes of Defibrillator Lead Implants Between High-Volume and Low-Volume Operators: Results From the Pacemaker and Implantable Defibrillator Leads Survival Study (”PAIDLESS”). J Invasive Cardiol. 2017;29(12):E184-E189.4. Chan NY, Kwong NP, Cheong AP. Venous access and long-term pacemaker lead failure: comparing contrast-guided axillary vein puncture with subclavian puncture and cephalic cutdown. Europace.2017;19(7):1193-1197.5. Gallik DM, Ben-Zur UM, Gross JN, Furman S. Lead fracture in cephalic versus subclavian approach with transvenous implantable cardioverter defibrillator systems. Pacing Clin Electrophysiol.1996;19(7):1089-1094.6. Belott P. How to access the axillary vein. Heart Rhythm.2006;3(3):366-369.7. Liccardo M, Nocerino P, Gaia S, Ciardiello C. Efficacy of ultrasound-guided axillary/subclavian venous approaches for pacemaker and defibrillator lead implantation: a randomized study. J Interv Card Electrophysiol. 2018;51(2):153-160.8. Squara F, Tomi J, Scarlatti D, Theodore G, Moceri P, Ferrari E. Self-taught axillary vein access without venography for pacemaker implantation: prospective randomized comparison with the cephalic vein access. Europace. 2017;19(12):2001-2006.9. Bongiorni MG, Proclemer A, Dobreanu D, et al. Preferred tools and techniques for implantation of cardiac electronic devices in Europe: results of the European Heart Rhythm Association survey.Europace. 2013;15(11):1664-1668.10. Vogler J, Geisler A, Gosau N, et al. Triple lead cephalic versus subclavian vein approach in cardiac resynchronization therapy device implantation. Sci Rep. 2018;8(1):17709.11. Hadjis A, Proietti R, Essebag V. Implantation of cardiac resynchronization therapy devices using three leads by cephalic vein dissection approach. Europace. 2017;19(9):1514-1520.12. Kajiyama T, Ueda M, Ishimura M, et al. A novel technique for ligation of the cephalic vein reduces hemorrhaging during a two-in-one insertion of dual cardiac device leads. Indian Pacing Electrophysiol J. 2018;18(4):152-154.

Samia ricini, a gigantic saturniid moth, has the potential to be a novel lepidopteran model species. Since S. ricini is much more tough and resistant to diseases than the current model species Bombyx mori, the former can be easily reared compared to the latter. In addition, genetic resources available for S. ricini rival or even exceed those for B. mori: at least 26 eco-races of S. ricini are reported and S. ricini can hybridise with wild Samia species, which are distributed throughout Asian countries, and produce fertile progenies. Physiological traits such as food preference, integument colour, larval spot pattern, etc. are different between S. ricini and wild Samia species so that those traits can be the target for forward genetic analysis. In order to facilitate genetic research in S. ricini, we determined the whole genome sequence of S. ricini. The assembled genome of S. ricini was 458 Mb with 155 scaffolds, and the N50 length of the assembly was approximately 21 Mb. 16,702 protein coding genes were predicted in the assembly. Although the gene repertoire of S. ricini was not so different from that of B. mori, some genes, such as chorion genes and fibroin genes, seemed to have specifically evolved in S. ricini.

Background The covid 19 positive patient who is subject to a hyperinflammatory condition associated with lung injury with the development of pneumonia is hospitalized in the intensive care unit. Before resolving and overcoming the “cytokine storm”, with overexpression of pro-inflammatory interleukins (IL-, Il-6), this patient will be intubated for more than 48 hours and therefore needs adequate nutrition. Experimental approach Malnutrition can lead to sarcopenia with a decrease in lean body mass and worsening of the inflammatory state underway. In addition, severe debilitation, if not corrected with adequate nutrition, can greatly lengthen rehabilitation times with prolonged hospitalization, increased costs and reduced turn over already in crisis due to the health emergency caused by coronavirus. Key Results The aim of this study is to focus attention on the nutritional importance that must be provided in case of covid 19 together with pharmacological treatments to lower the number of circulating proinflammatory cytokines. Conclusions Oral, enteral and parenteral nutrition should always be carried out according to the patient’s condition and, in the case of a hyperinflammatory patient, such as the one affected by covid 19, it has been shown that the supplementation of amino acids helps to lower the inflammatory state and promotes normal recovery physiological. Keywords: amino acids, nutrition, covid, glutamine, hyperinflammatory, sarcopenia, cytokine.

Pulmonary artery (PA) band is done in a variety of congenital heart diseases (CHDs) with the primary goal of reducing pulmonary overcirculation. Its use has declined during the last two decades, however, its role still exists in classic univentricular heart with unrestricted pulmonary blood flow. PA banding in univentricular morphology with transposition of great arteries (TGA) can be extremely morbid. Our patient had ST segment elevation in inferior leads after banding, indicating acute ischemia in right coronary artery territory. We hypothesize that, the cause for this was sudden shift of volume to the rudimentary camber through the bulboventricular foramen after PA banding, causing subendocardial ischemia. Interpretation of electrocardiogram (ECG) and subsequent management is not straightforward in this scenario .We hereby describe successful management of sudden ST segment changes observed in immediate post-operative period after PA banding for univentricular, TGA heart in an 8 month old infant.

Mediastinitis is a serious complication after cardiac surgery. While bacteria are the more common pathogens, fungal infections are rare. Post-operative Aspergillus mediastinitis is considered to be a catastrophic infection, affecting patients with specific predisposing factors undergoing cardiothoracic surgery. The patient outcome after aspergillus mediastinitis is extremely poor despite antifungal therapy and surgery. The diagnosis is usually delayed and relies on direct visualization and culture. Clinical features of post-operative Aspergillus mediastinitis could be minimal, underlining the necessity for a low index of suspicion in cases of culture-negative mediastinitis. Antifungal therapy including amphotericin B or voriconazole along with surgical debridement forms the mainstay of treatment.

Reduction of pulmonary fibrotic status and reduction of hyperinflammation is essential to combat SARS-CoV-2 and avoid death. Many authors have divided the SARS-CoV-2 infection into three stages, the second and third of which are purely inflammatory and fibrotic. Waiting for the development of antiviral drugs and vaccines to give good results, the best pharmacological goal is the reduction of proinflammatory molecules. This leads to less formation of fibrotic tissue and to the resolution of the patient’s respiratory problems. In fact, in phase 3, the most serious, there is a state of overexpression of the immune system with consequent assault on all tissues and damage to the lungs. Sars cov 2 pneumonia is characterized by “cytokine storm” and can lead to death. Acting early and with pirfenidone combination therapy can be effective. The IL-6 or IL-1 inhibitors, chloroquine / hydroxychloroquine and colchicine, which are demonstrating their anti-inflammatory efficacy, when combined with an anti-inflammatory and antifibrotic agent, such as pirfenidone, can have a winning result. The effective combined terepia allows to use non-lethal dosages and affects all the pathological steps induced by the virus. Pirfenidone has been used for years in lung diseases and has been shown to have good clinical success and good safety and tolerability.The purpose of this study is to explain the pharmacological logic behind the use of a combination therapy as an effective and safe remedy to reduce pneumonia and the consequent death from Sars CoV 2. Keywords: pirfenidone, fibrotic, inflammation, cythokine, interleukin, Sars-CoV-2.

The effects of forest conversion from natural forest to agricultural system on soil microbial composition still need further study. Especially, impact on soil function after forest conversion is not yet known. In this study, by using metagenomic sequencing as well as 16S and ITS sequencing technology, we evaluated the soil microbial composition, diversity and functions based on a large number of soil samples of tropical rainforest and rubber plantation across the whole island of Hainan, south China. The results showed that (1) forest conversion changed microbial composition from bacterial groups of Proteobacteria to Chloroflexi, and fungal groups from Basidiomycota to Ascomycota. (2) The bacterial alpha diversity, beta diversity as well as the total diversity did not decrease after forest conversion. However, beta diversity of fungal community reduced resulting a net loss of total OTU richness. (3) There was no difference in soil functional compositions and diversity between rubber plantations and rainforest, however, the relative gene abundance of most COG functions, KEGG functions, CAZy functions as well as Antibiotic gene were significantly different between rubber plantation and tropical rainforest. (4) Soil pH and environmental heterogeneity were the main driver for microbial taxonomic composition and gene functional composition. Land use did not result in changes of functional gene composition, but the relative abundance of functional gene. The changed relative abundance gene would alter the ecosystem processes. In conclusion, our results confirmed that land use changes alter the soil microbial community structure and can have profound effects on ecosystem functions and processes.

Peripartum use of Extracorporeal Membrane Oxygenation (ECMO) in a Patient Suffering from COVID-19 Severe Acute Respiratory Distress Syndrome (ARDS): A Case ReportJay Conhaim, MD1, Braxton Forde, MD2, Beth Weishaupt ACNP-BC1, Kara Markham, MD2, William Hurford, MD1, C Jesse Pickard-Gabriel, MD11: Department of Anesthesia and Critical Care Medicine, University of Cincinnati Medical Center, Cincinnati, OH USA 452672: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Cincinnati Medical Center, Cincinnati, OH USA 45267Short title – The Role of VV ECMO in Severe Peripartum COVID-19Corresponding Author: C Jesse Pickard-GabrielAddress: Department of Anesthesia and Critical Care, Medical Sciences Building Room 3502, 231 Albert Sabin Way, PO Box 670531, Cincinnati, OH, USA, 45267-0531.Phone: 513-558-2402Email: PickardCJ@ucmail.uc.eduKeywords: ECMO, Pregnant, COVID-19, ARDSAbstractWe present a 27 year old G2P1001 woman at 29 weeks and 0 days with coronavirus disease 2019 (COVID-19) and subsequent developed of severe ARDS. Following tracheal intubation and hospitalization, the patient and fetus were monitored for seven days. Secondary to worsening oxygenation that was refractory to ventilator and positioning changes, a cesarean was performed at 30 weeks and 0 days with immediate veno-venous (VV) extracorporeal membrane oxygenation (ECMO) cannulation. The patient was transferred to an ECMO referral center and was able to be successfully decannulated and extubated. This discussion focuses on COVID-19 and ARDS in pregnancy with the treatment therein.Tweetable abstract:Successful use of VV ECMO to treat severe peripartum COVID-19 PNA in a 27 year old G2P1001 at 29 weeks gestation.Glossary of TermsARDS – Acute Respiratory Distress SyndromeAFE – Amniotic Fluid EmbolismCOVID-19 – Corona Virus Disease 2019ECMO – Extracorporeal Membrane OxygenationFdO2 – Fraction of Delivered Oxygen (via ECMO)FiO2 – Fraction of Inspired Oxygen (via ventilator)PEEP – Positive End Expiratory PressureSARS-CoV-2 – Severe Acute Respiratory Syndrome Coronavirus 2SpO2 – Oxygen SaturationVV – Veno VenousIntroductionThe utilization of extracorporeal membrane oxygenation (ECMO) in the setting of severe acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) infection has been reported in limited numbers. As of this writing the Extracorporeal Life Support Organization has registered 364 confirmed COVID-19 cases on ECMO with 36% survival to discharge1 and there have been no reports of ECMO use in the peripartum setting for severe COVID-19 pneumonia. This case discussion focuses on the peri-partum considerations of veno-venous (VV) ECMO for a patient who developed respiratory failure due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and subsequent development of COVID-19. Heath Insurance Portability and Accountability Act authorization has been obtained from the patient.CaseA 27 year-old G2P1001 woman who tested positive for SARS-CoV-2 subsequently developed COVID-19 and was admitted to the hospital three days later. She was 28 weeks and 3 days pregnant by 8-week ultrasound at time of diagnosis and was initially being monitored at home. On the day of admission, she had developed acute shortness of breath and mild tachycardia, but remained afebrile. Despite 15 l/min oxygen via a non-rebreather mask, she was unable to maintain oxygen saturations (SpO2) above 92%. Her trachea was intubated, and she was transferred to the intensive care unit. She was thrombocytopenic (73,000/µl), lymphopenic (500/mL, 12%), and mildly anemic (hemoglobin of 11.1 g/dl). C-reactive protein was slightly elevated (5.3 mg/l) as was interleukin-6 (11.48 pg/ml). A chest radiograph demonstrated bilateral mild atelectasis and mild opacification of the right lung base. The obstetric service diagnosed pre-eclampsia without severe features on the basis of mild hypertension and a protein to creatinine ratio that was elevated to 0.35. Magnesium therapy was deferred given her respiratory status. Continuous tocometry and fetal heart rate monitoring demonstrated a normal fetal heart rate without regular contractions.Despite transient improvement and extubation on Day 2, she worsened and required re-intubation on Day 3 for recurrent hypoxemic respiratory failure. There was concern for developing fetal hypoxemia, although three times daily fetal nonstress tests were reassuring. Hydroxychloroquine was administered on Days 3-4, and remdesivir was initiated on Day 5. Her hypoxemia continued to worsen despite fraction of inspired oxygen (FiO2) 1.0, positive end-expiratory pressure (PEEP) of 12 cm H2O, chemical paralysis, and prone positioning.Due to significantly worsening respiratory status, a cesarean delivery was performed on Day 7 (30 weeks gestation) prior to completion of a full course of betamethasone therapy for fetal lung maturity. Immediately following an uneventful delivery, the patient received a heparin loading dose. A 25-French right femoral drainage cannula and a 19-French right internal jugular return cannula were placed. Initiation of veno-venous (VV) ECMO improved the SpO2 to 100%. The uterus was closed, however given immediate initiation of anticoagulation, the abdomen was temporarily closed with a vacuum-assisted dressing to better monitor hemodynamics and intraabdominal bleeding. The patient received a dose of human convalescent serum and was transferred to an ECMO referral center for further care.At the referral center, the patient was supported with VV ECMO flows of 4.19 l/min (cardiac index of 2.08 l/min/m2), Fraction of Delivered Oxygen (FdO2) of 100% and a sweep flow of 2 l/min, titrating the FdO2 to keep SpO2> 85% and PaCO2 +/- 5 mmHg of 40 mmHg. She did not require ongoing neuromuscular blockade. Pressure-controlled ventilation was continued with a plateau pressure of 24 cm H2O, PEEP of 10 cm H2O, and a respiratory rate of 14 breaths/min. Tidal volumes were approximately 350mL (5.4mL/kg ideal body weight.) A repeat SARS-CoV-2 test was sent, which confirmed the diagnosis. Vancomycin and cefepime were begun for empiric coverage of likely bacterial superinfection. Low dose norepinephrine and vasopressin infusions were required to maintain mean arterial blood pressures above 65mmHg while using a furosemide infusion for diuresis. There was no evidence of ongoing bleeding, and her abdominal wall was closed two days after her cesarean delivery.On Day 8, FiO2 was decreased to 0.3, and PEEP was decreased to 10 cm H2O. ECMO flows remained unchanged and FdO2 was decreased to 90% with a sweep flow of 2 l/min. On Day 9, ECMO flows remained unchanged, FdO2 was decreased to 35%, and the sweep flow was capped. Ventilator settings remained unchanged while tidal volumes increased to 400mL. Pan-sensitiveStaphalococcus aureus was cultured from a sputum culture collected on Day 1, and antibiotics were changed to cefazolin monotherapy.On Day 10, with continued improvement, the patient was successfully decannulated at the bedside after capping the ECMO circuit for > 12 hrs. Remdesivir therapy, which was discontinued at the time of transfer for administrative reasons, was re-initiated to complete a 10-day course. Vasoactive infusions were discontinued on Day 12, and the patient was extubated on Day 13, and weaned off oxygen therapy on Day 15.CommentAt the time of this report there have been almost 2,000,000 confirmed COVID-19 cases worldwide with 126,140 confirmed deaths in 213 countries2. The natural history, pathophysiology, epidemiology and associated facets of COVID-19 are still being characterized as the pandemic is ongoing. However, it is understood that COVID-19 is known to prey on patients with existing medical co-morbidities3,4. COVID-19 is seemingly less symptomatic in the parturient as compared to the general public5, which is in stark contrast to the effects of SARS-CoV-1 and MERS-CoV on pregnant women6. The physiologic changes of pregnancy would seemingly engender an increased risk from a SARS-CoV-2 infection. The decrease in functional residual capacity during pregnancy, as well as decreased chest wall and lung compliance in the third trimester7, might limit the ability of pregnant women to compensate in the setting of SARS-CoV-2 associated lung disease. Early reports, however, suggest a decreased mortality risk in the parturient5. It is hypothesized that a hormone-mediated shift towards T-helper 2 cell-mediated immunity during pregnancy may result in an anti-inflammatory response which could ultimately have protective effects against SARS-CoV-28.Elevated SpO2 targets to preserve placental oxygenation and avoid placental vasoconstriction necessitate greater levels of oxygen support in pregnant women with ARDS9. The absence of fetal distress and ability to maintain adequate maternal oxygenation initially informed the patient’s trajectory of care, however, worsening maternal hypoxemia resulted in fetal delivery as her ability to maintain adequate oxygenation waned despite appropriate positioning maneuvers10,11.The decision to delay delivery of the fetus until the mother wasin extremis directly led to the decision to initiate ECMO at the time of delivery. The mother clearly met criteria for VV ECMO initiation in the hours leading up to delivery, but she improved in short order following delivery and met criteria for decannulation within 24hrs. This raises the obvious question of whether VV ECMO was necessary. Could ECMO have been avoided if the patient had been delivered sooner? Should the medical team have waited to see if delivery improved pulmonary status enough to obviate the need for VV ECMO?It seems logical that delivery of the fetus generally improves the respiratory status of a mechanically ventilated mother, however, this effect may only be seen in severe respiratory disease,11 and there may be limited benefit if tracheal intubation has occurred due to non-respiratory pathology12,13. The highest benefit is seen in instances of mechanical ventilation for obstetric reasons14. Additionally, fluid shifts at the time of delivery, often worse in mothers with cardio-pulmonary problems and/or preeclampsia, can lead to poor outcomes. Other uncommon but acute peri-partum complications such as hemorrhage and amniotic fluid embolism (AFE) can be life-threatening in the absence of existing pathology. This patient had no pre-existing cardiac problems, but the additional pulmonary burden of fluid shifts could have proven catastrophic given her pre-delivery PaO2. The mother’s inability to compensate for additional complications such as severe hemorrhage or AFE, justifies planning to cannulate as a safe and reasonable approach. Furthermore, given her high risk of postpartum hemorrhage with necessary initiation of anticoagulation, leaving the abdomen open afterwards, while beneficial for close monitoring and bleeding management, could have likely been avoided if delivery had occurred sooner in the hospital course. Regarding neonatal benefits of delivery, prolonged ventilator support has been associated with increased rates of perinatal asphyxia and while that scenario was unlikely in this case due to the reassuring fetal tracing, expedited delivery is always a consideration15.The timing of delivery and initiation of ECMO in such a critically ill parturient with COVID-19 obviously is not well established. Had the mother been delivered prior to meeting criteria for VV ECMO cannulation, she may have avoided the need for cannulation. However, it is not easy to balance the needs of the mother with the fetus in the setting of a novel and often deadly disease. While this neonate has done well postnatal, consideration for earlier administration of antenatal corticosteroids is important to achieve maximal benefit, as this patient did not receive her first dose of antenatal steroids until the morning of delivery. Regarding the mother, the decision to plan for VV ECMO cannulation following delivery was likely the safest option for the patient by the time that she delivered. While it is possible that the patient would have improved over the two to four hours following delivery, the decision to cannulate immediately was well tolerated and ultimately may have been life-saving for this patient. VV ECMO seems to be a reasonable and feasible option as a life-saving therapy in the setting of severe ARDS and peripartum COVID-19 PNA.Special Thanks To – Dr. Alex Kobzik, for providing care to this patient prior to transfer and help in gathering data about her course.Disclosure of Interests:The authors report no financial disclosures or conflicts of interest related to this project.Contribution to authorship:Jay Conhaim: This author prepared the initial manuscript and compiled references.Beth Weishaupt: This author gathered data and lab results from the both hospitals and helped to build the timeline leading up to cannulation.Braxton Forde: This author edited the manuscript, contributing to the evaluation and discussion of the peripartum management of the mother and baby.William Hurford: This author edited the manuscript and provided specific critical-care related insight.Kara Markham: This author edited the manuscript and comment with specific regards to the peripartum considerations of mother and baby.C Jesse Pickard-Gabriel (corresponding author): This author edited the manuscript and wrote the comment.Details of Consent:We affirm that written consent from the patient was obtained for permission to write and submit this case report.Funding:No funding was received by any of the authors for the work provided related to this project.ReferencesExtracorporeal Life Support Organization [internet]. https://www.elso.org/Home.aspx. accessed 2020 Apr 16.World Health Organization [internet]. https://www.who.int/emergencies/diseases/novel-coronavirus-2019. accessed 2020 Apr 16.Ruan Q, Yang K, Wang W , Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020; published online Mar 3. DOI:10.1007/s00134-020-06028-zGuan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020; published online Feb 28. DOI: 10.1056/NEJMoa2002032Schwartz D. An analysis of 38 pregnant women with COVID-19, their newborn infants, and maternal fetal transmission of SARS-CoV-2: maternal coronavirus infections and pregnancy outcomes. Arch Pathol Lab Med. 2020; published online Mar 17. DOI: 10.5858/arpa.2020-0901-SAWong SF, Chow KM, Leung TN, et al. Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome. Am J Obstet Gynecol. 2004; 191(1):292-7.Gardner MO, Doyle NM. Asthma in pregnancy. Obstet Gynecol Clin North Am. 2004; 31(2):385-413.Dashraath P, Jing Lin Jeslyn W, Mei Xian Karen L, Li Min L, Sarah L, Biswas A, Arjandas Choolani M, Mattar C, Lin SL. Coronavirus disease 2019 (COVID-19) pandemic and pregnancy. Am J Obstet Gynecol.2020; published online Mar 23. DOI: 10.1016/j.ajog.2020.03.021.Dharani K, Narendra DM, Kalpalatha KG. Acute respiratory distress syndrome in pregnancy. In: Jeffrey P, Phelan LDP, Michael R. Foley, George R. Saade, Gary A Dildy, and Michael A. Belfort, eds.Critical Care Obstetrics. Wiley- Blackwell; 2019:403-418.Schwaiberger D, Karcz M, Menk M, Papadakos P, Dantoni S. Respiratory Failure and Mechanical Ventilation in the Pregnant Patient. Crit Care Clin. 2016; 32(1):85-95Lapinsky SE, Rojas-Suarez JA, Crozier TM, Vasquez DN, Barrett N, Austin K, Plotnikow GA, Orellano K, Bourjeily G. Mechanical ventilation in critically-ill pregnant women: a case searies.Int J Obstet Anesth. 2015; 24(4):323-8Tomlinson MW, Caruthers TJ, Whitty JE, Gonik B. Does delivery improve maternal condition in the respiratory-compromised gravida?Obstet Gynecol. 1998; 91(1):108–11.Daily WH, Katz AR, Tonnesen A, Allen SJ. Beneficial effect of delivery in a patient with adult respiratory distress syndrome.Anesthesiology . 1990; 72(2):383–6.Hung CY, Hu HC, Chiu LC, Chang CH, Li LF, Huang CC, Kao CC, Chen PJ, Kao KC. Maternal and neonatal outcomes of respiratory failure during pregnancy. Journal of the Fomosan Medical Association. 2018; 118:413-420.Catanzarite V, Wilms D, Wong D, Landers C, Cousins L, Schrimmer D. Acute Respiratory Distress Syndrome in Pregnancy and the Puerperium: Causes, Courses, and Outcomes. Obstet Gynecol. 2001; 97(5):760-764.

Objective: Assess efficacy and safety of labour induction in women with one or more previous caesarean deliveries during second and third trimester pregnancy termination or intrauterine fetal death. Design: Retrospective single-centre study between 2007 and 2018. Setting: Lille, France Population: 136 women with history of previous caesarean deliveries (CD) (study group) and 272 controls undergoing labour induction for pregnancy termination or intrauterine fetal death. Methods: Before 32 weeks, misoprostol 400 μg was given orally every 3 hours up to a maximum of five doses in 24 hours. Study group received half doses. After 32 weeks, oxytocin infusion, misoprostol (PGE1) or PGE2 (dinoprostone) were used according to the Bishop score. Main outcome measures: Vaginal delivery within the 24 hours after induction without uterine rupture or severe post-partum haemorrhage defined as blood loss > 1 litre (PPH). Results: Vaginal delivery within the 24 hours after induction without uterine rupture or PPH was 83.5% in the study group versus 92.6% in the control group (p=0.005). 5 (3.7%) uterine ruptures occurred in the study group, 1.7% in case of one previous CD and 15.8% in case of 2 or more previous CD. There were more severe PPH in the study group (6.7% versus 2.2% p=0.03), but no difference was found between women with one or more previous CD. Conclusions: Women with 2 or more prior CD should be informed that they are at higher risk of complications such as uterine rupture and severe post-partum haemorrhage.

Background: Primary cardiac neoplasms are rare and occur less commonly than metastatic disease of the heart which sarcomas are the largest group of them and have a mesenchymal origin. metastases to or direct invasion of the heart are far more common, and many tumor types are reported in the literature such as breast cancer, lung cancer, melanoma and various sarcomas. The prognosis after surgery is usually excellent in the case of benign tumors, but the prognosis of malignant tumors remains dismal. Patients and methods: We are about to report through 5 cases of malignant cardiac tumors hospitalized in our department and treated later with cardiac surgery, the subtypes of cardiac masses and their diagnosis and prognosis (follow-up) features with literature review. Results: Five cases of cardiac neoplasms had been reported in this work; that can be classified in one case of primary cardiac origin and 4 cases as secondary to metastases (breast cancer, lung cancer, osteosarcoma and mediastinal thymoma). Echocardiogram was the main exploration technique to be performed and thoracic CT was performed in all cases. Cardiac surgery was the main treatment in only one case, but the others palliative treatment was the case. Conclusion: Malignant cardiac masses are infrequent and often asymptomatic, most of the time they are secondary to extra cardiac tumor. Early diagnosis of cardiac tumors necessitates a high level of suspicion. Therefore, surgery remains the cornerstone in the therapy of cardiac sarcomas and it should be attempted once it is technically feasible.

Plant interactions play key roles in coexistence, where intraspecific neighbors must compete more intensely than interspecific neighbors to promote species coexistence. But because plastic responses can alter traits and interactions, including intraspecific interactions, plasticity can hinder or promote species coexistence. Whether plasticity induced by different types of competitors can impact mechanisms of coexistence remains unknown. To address this, I used a transplant experiment to induce plastic responses with intraspecific or interspecific interactions. Then, I investigated the effects of the induced phenotype on new intraspecific interactions. The interspecific interaction treatment induced plastic responses, producing facilitative outcomes. In the subsequent intraspecific interactions, interspecific-induced individuals exhibited more competitive intraspecific interactions than intraspecific-induced individuals, even though the initial induced effect was positive. This study demonstrates that interspecific interactions may play an indirect role in stabilizing niche mechanisms via induced plasticity, furthering our understanding of how plastic responses impact interactions and species coexistence.

In district Haripur, KPk, Pakistan Treepie Dendrocitta vagabunda parvula (Latham, 1790) (Passeriformes: Corvidae), is a widespread resident bird commonly found. Feeding and Food habits of Treepie were studied by direct focal observation method analysis of gut content and faecal matter. Treepie prefers tree and cultivation areas insects for foraging activities, feeding on animal and plant is an omnivore items ranging from vertebrate species to invertebrate. Feeding upon like red palm weevil, grasshopper, cockroaches, banana stem weevil, nestlings of squirrel and house rat, it feeds up on many pests of agricultural crops Treepie is an important biocontrol agent in the agro ecosystem of the region

Background: In this study, we evaluated the difference in the tumor mutational burden (TMB) score between primary and metastatic lesions in pan-cancer and the different cut-offs for guiding immune checkpoint inhibitors (ICIs) prognosis. Methods: We screened 1661 pan-cancer cases from the cBioPortal database. The Kaplan-Meier method was applied to obtain survival curves that were compared using the log-rank test. The X-tile model was used to determine the optimal cut-off values of TMB. Results: Our results showed that the tissues obtained from the metastatic lesions had more co-occurring gene mutations than the primary lesions (P<0.05, Q<0.05). Moreover, tissues from patients with metastatic lesions had a higher TMB score than those from patients with primary lesions (P = 0.024). According to the median cut-off values of TMB from the primary and metastatic lesions, we analyzed the overall survival (OS) in the low TMB and high TMB groups, respectively. The results showed different OS for the two TMB groups in primary and metastatic lesions. Subsequently, we analyzed the optimal cut-off values of TMB score to predict survival in primary and metastatic lesions based on the X-tile model. The optimal cut-off value for the test tissue from primary lesions was 20.19 (P<0.001). Importantly, the optimal cut-off value for test tissue from metastatic lesions was 10.18 (P < 0.001). Conclusion: TMB detection from primary and metastatic lesions should be considered separately to predict survival for ICIs treatment.

Road networks cause land degradation by mean of disturbances that can alter the biodiversity and the functioning of the Caatinga ecosystems. We tested the hypotheses that (i) Caatinga vegetation near roads is less taxonomically, functionally and phylogenetically diverse, (ii) phylogenetically and functionally more clustered than vegetation further from roads, (iii) plant traits associated with herbivory deterrence are conserved within the phylogenetic lineages, and (iv) Caatinga vegetation near roads selects for disturbance-related traits. We sampled herbaceous and woody component of vegetation in four plots near roads and four plots further from roads to test these hypotheses. Sampled species were classified according to their resprouting capacity, nitrogen fixation, succulence/spines, urticancy/toxicity, lifeform, endozoochory, maximum height and maximum diameter, before we calculated the taxonomic, functional and phylogenetic diversity of plant communities. Species richness, taxonomic, functional and phylogenetic diversities were lower in plots close to the roads, confirming roads as sources of disturbances. The phylogenetic structure of the Caatinga vegetation near roads was clustered, indicating environmental filtering by herbivory as the main pervasive disturbance in Caatinga ecosystems, since traits related to herbivory deterrence were conserved within phylogenetic lineages and were filtered in near roads. Thus, roads should be considered conduits of land degradation causing taxonomic, phylogenetic and functional impoverishment of Caatinga vegetation.

Ultrasound-detected structural anomalies have an impact on fetal mortality and morbidity. Prenatal Exome Sequencing is incorporated into clinical care pathways for paediatric populations but maybe used to delineate the prognosis of fetal structural anomalies. This paper reviews the literature defining the clinical utility of prenatal ES and discusses the potential promise and challenges for implementation of this technology into clinical practice. Prospective case selection with accurate and informative pre-test counselling by multidisciplinary, clinical genetic-led teams is imperative. Robust, regulated laboratory sequencing, informative bioinformatic pathways with variant identification and conservative matching with the phenotype (within clinical review panels) is also important.

The aim of this multicenter retrospective study was to evaluate the incidence of hyperprogressive disease after treatment with pembrolizumab as a second-line treatment in patients (n=167) with non-small-cell lung cancer (NSCLC) with metastatic disease whose tumors expressed programmed death-ligand-1 in ≥1% and to search for factors associated with its development. All patients received platinum-containing chemotherapy as a first-line treatment. The neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and their derivations were retrospectively analyzed. The psoas major muscle area (PMMA) was calculated at the L3 position on computed tomography before chemotherapy and immunotherapy. Patients with ∆PMMA≥10% were considered to have sarcopenia (low muscle mass). We also performed multinomial logistic regression to estimate the effects of hematological biomarkers and ∆PMMA on the response to immunotherapy. Hyperprogressors (HPs) had significantly higher NLRs, PLRs and ∆PMMA levels than the other patients. Moreover, in multivariate regression analysis, higher levels of ∆PMMA were associated with a decreased likelihood of being a progressor (P) (OR, 0.81; 95% CI, 0.65-0.99; p=0.047) or a nonprogressor (NP) (OR, 0.76; 95% CI, 0.62-0.94; p=0.012) vs an HP. In multivariate analysis, higher NLRs tended to decrease the likelihood of being a P vs an HP (OR, 0.66; 95% CI, 0.42-1.06; p=0.09) and significantly decrease the likelihood of being an NP vs an HP (OR, 0.44; 95% CI, 0.28-0.69; p<0.0001). Our data suggest that a high pre-immunotherapy NLR and the presence of sarcopenia are potential risk factors for the development of hyperprogressive disease.