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Anisah Yahya

and 3 more

Objective: The use of antenatal corticosteroids beyond 34 weeks of gestation remains a debate. This study sought to determine the effect of use of antenatal corticosteroids in late preterm delivery on neonatal morbidity. Design: It was a randomized double-blind placebo and active controlled multi arm trial. There were two study groups and one control group. Setting: It was conducted at the department of Obstetrics and Gynaecology and the Department of Paediatrics of Ahmadu Bello University Teaching Hospital Zaria. Population: Pregnant women at 34 weeks 0 days to 36 weeks 6 days of gestation scheduled for elective/emergency delivery were recruited for the study. Methods: The study groups had dexamethasone and betamethasone respectively while the control group had a placebo. Main outcome: The primary outcome was incidence of respiratory distress syndrome. Results: A total of 138 mothers and 146 preterm neonates were included in the study with 48 exposed to placebo, 49 exposed to betamethasone and 49 exposed to dexamethasone. A pairwise analysis was done to test for difference between the groups. There was no statistically significant difference in the incidence of respiratory distress syndrome between the dexamethasone vs placebo (p= 0.98, RR 1, CI 0.06-16.89), betamethasone vs placebo (p= 0.98 RR 1, CI 0.09-11.55) and dexamethasone vs betamethasone (p=0.32, RR 0.5, CI 0.09-2.42) Conclusion: Antenatal corticosteroids may decrease the need for neonatal resuscitation at birth in late preterm neonates.

Alessia Guerrieri

and 17 more

Ice-free areas are increasing worldwide due to the dramatic glacier shrinkage and are undergoing rapid colonization by multiple lifeforms, thus representing key environments to study ecosystem development. Soils have a complex vertical structure. However, we know little about how microbial and animal communities differ across soil depths and development stages during the colonization of deglaciated terrains, how these differences evolve through time, and whether patterns are consistent among different taxonomic groups. Here, we used environmental DNA metabarcoding to describe how community diversity and composition of six groups (Eukaryota, Bacteria, Mycota, Collembola, Insecta, Oligochaeta) differ between surface (0-5 cm) and relatively deep (7.5-20 cm) soils at different stages of development across five Alpine glaciers. Taxonomic diversity increased with time since glacier retreat and with soil evolution; the pattern was consistent across different groups and soil depths. For Eukaryota, and particularly Mycota, alpha-diversity was generally the highest in soils close to the surface. Time since glacier retreat was a more important driver of community composition compared to soil depth; for nearly all the taxa, differences in community composition between surface and deep soils decreased with time since glacier retreat, suggesting that the development of soil and/or of vegetation tends to homogenize the first 20 cm of soil through time. Within both Bacteria and Mycota, several molecular operational taxonomic units were significant indicators of specific depths and/or soil development stages, confirming the strong functional variation of microbial communities through time and depth. The complexity of community patterns highlights the importance of integrating information from multiple taxonomic groups to unravel community variation in response to ongoing global changes.

Rebecca Furze

and 16 more

AIM: To improve the tolerability and therapeutic application of histone deacetylase inhibitors (HDACi), by application of an esterase-sensitive motif (ESM), to target pharmacological activity directly to mononuclear myeloid cells expressing the processing enzyme carboxylesterase-1 (CES1). METHODS. This first-in-human study comprised of single and multiple ascending dose cohorts to determine safety and tolerability. Pharmacodynamic parameters included acetylation, cytokine inhibition and intracellular concentrations of processed acid metabolite in isolated monocytes. Mechanistic work was conducted in vitro and in a CES1/Es1elo mouse strain. RESULTS. ESM-HDAC391 was well tolerated whilst showing robust targeted mechanistic engagement, as demonstrated by selective retention of compound and increased acetylation in monocytes plus inhibition of ex vivo stimulated cytokine production. Importantly, common clinical HDACi toxicities were not observed. ESM-HDAC391 treatment was accompanied by the novel finding of a dose-dependent monocyte depletion that was transient and reversible. In-depth characterisation of monocyte depletion in a transgenic mouse model (CES1/Es1elo) suggested that CSF1R loss on circulating cells contributes to ESM-HDAC-mediated depletion. Further mechanistic investigations using human monocytes in vitro demonstrated HDACi-mediated change in myeloid fate through modulation of CSF1R and downstream effects on cell differentiation. CONCLUSION. These findings demonstrate selective targeting of monocytes in humans using the ESM approach and identify monocytopaenia as a novel outcome of ESM-HDACi treatment, with implications for the potential benefit of these molecules in myeloid-driven diseases.

Tilde Østborg

and 5 more

Objective: To explore the duration of the active phase of the second stage of labour in relation to maternal prepregnant body mass index (BMI). Design: Retrospective cohort study. Setting: Labour wards of three Norwegian university hospitals, 2012-2019. Population: Nulliparous and parous women without previous caesarean section with a live singleton foetus in cephalic presentation and spontaneous onset of labour, corresponding to the Ten Group Classification System (TGCS) group 1 and 3. Methods: Women were stratified to BMI groups according to WHO classification, and estimated median duration of the active phase of the second stage of labour was calculated using Kaplan-Meier analyses. We performed stratified analyses in women with and without epidural analgesia and oxytocin augmentation. Finally, we calculated the Hazard Ratio (HR) of delivery using Cox regression analyses. Caesarean sections and operative vaginal deliveries during the active phase were censored. Main Outcome Measures: Estimated median duration of the active phase of second stage of labour. Results: The final study population comprised 23516 women in TGCS group 1 and 27255 in group 3. Increasing BMI was associated with shorter estimated median duration of the active phase in both TGCS groups. The pattern remained when performing stratified analyses for epidural and oxytocin analgesia. The HR for delivery increased significantly with increasing BMI analysed as a continuous variable; HR 1,019 (95%CI 1.016-1.023) in TGCS group 1 and HR 1,017 (95%CI 1.014-1.020) in TGCS group 3. Conclusion: Increasing BMI was associated with shorter estimated median duration of the active second stage Funding: None.

Sarah Walker

and 6 more

Objective: Procalcitonin (PCT) is an established biomarker for bacterial sepsis in the non-pregnant population. We aimed to evaluate PCT levels in women and their neonates managed with suspected intrapartum bacterial sepsis, to determine if PCT could be utilised to optimise diagnosis and management. Design: Prospective observational cohort study. Setting: University Hospitals of Bristol and Weston NHS Foundation trust. Population: 117 women and their neonates managed for suspected intrapartum sepsis from June-October 2020. Methods: PCT levels were measured in addition to routine biomarkers white cell count and c-reactive protein, in women and their neonates during initial septic screen and follow up blood samples. Placentas underwent detailed histopathology. Main Outcome Measures: Maternal and neonatal parameters were used to categorise cases into: ‘high-suspicion bacterial sepsis (BS),’ ‘equivocal BS’ and ‘low-suspicion BS.’ Kruskal-Wallis test was performed comparing categories with biomarker values and placental histology scores. Results: PCT was raised in 6 women in the initial septic screen sample, compared to 100 with a raised CRP. There was a significant difference in maternal postnatal PCT results between ‘high-suspicion BS’ and ‘low-suspicion BS’ categories. 71.2% of placentas showed varying degrees of chorioamnionitis. Conclusions: In our cohort of women, 94.6% had normal PCT levels whilst in labour at the time of the septic screen, consistent with the low number of confirmed bacteraemia. This provides a basis that PCT may complement clinical judgement and interpretation of already utilised prognostic and diagnostic tests, in order to improve patient care in the management of intrapartum sepsis.

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Pre-eclampsia screening studies - overcoming intervention biasHS CuckleFaculty of Medicine, Tel Aviv University, Ramat Aviv, IsraelThe ASPRE trial established beyond doubt the efficacy of aspirin prophylaxis in women with positive multi-marker first trimester preeclampsia (PE) screening test results (Rolnik et al. N Eng J Med 2017;50:613-22). Screening combined maternal characteristics, blood pressure, uterine artery Doppler, maternal serum pregnancy associated plasma protein (PAPP)-A and placental growth factor (PlGF). Screen-positive women were randomised to aspirin or placebo and there was a 62% reduction of pre-term PE in the aspirin arm.Subsequently, a practical question has arisen regarding the maternal serum markers: which is superior, PlGF or PAPP-A? This is best answered by non-intervention studies of PE screening when all markers are measured prospectively. There are four such studies and all show that the detection rate for a fixed 10% false-positive rate was higher when PlGF was included compared with PAPP-A; the increase ranged from 5% to 7% (Cuckle. Ultrasound Obstet Gynecol 2022;??:??-??).However, a non-intervention study, despite not revealing the PE screening test report to clinicians and patients, does not preclude the use of aspirin in some women; for example, those with high risk characteristics are likely to be recommended treatment. Moreover, these occasional interventions might bias the PlGF versus PAPP-A comparison. This would occur as a consequence of simultaneous Down syndrome screening using the Combined Test, since that test report includes the PAPP-A level. If this marker was low, treatment might be recommended, leading to the prevention of some pre-term PE cases, a proportion of which are screen-positive. In the absence of intervention these screen-positive cases would be true-positive but actually become false-positive, hence reducing the detection-rate and slightly increasing the false-positive rate. These effects will be stronger for PAPP-A combinations. The standard Combined Test does not include PlGF yielding a bias towards superior PE screening performance for PlGF combinations.In the current analysis, data from two of the four non-intervention studies are reanalysed to adjust for this potential bias (Wright et al. BJOG 2022;??:??-??). In both combined 4.2% (1066/25,226) had taken aspirin, although for nearly all the treatment was sub-optimal compared with the ASPRE regimen of 150mg/night at <16-36 weeks. The reanalysis was by statistical modeling using the original ‘competing risks’ method. But additionally superimposed were simulations from an ‘imputation’ model, which re-assigned false-positives among the 1066 treated women to true- or false-positive according to the probability of reduction in pre-term PE found in ASPRE.The model predicted that the increase in detection rate for a 10% false-positive rate when PlGF was included compared with PAPP-A was 7.0% and this reduced to 6.4% following imputation. Hence, even adopting the extreme assumption that intervention was at an optimal level, the bias in favour of PlGF was small. The authors also modeled combinations without blood pressure or uterine artery Doppler and the bias was proportionally similar or smaller.Clinical studies are often marred by subtle bias, and once discovered it is vital to assess whether the results were materially affected. The current publication is exemplary in using imputation modeling to confirm the superiority of PlGF over PAPP-A.(500 words)

Berhane Worku

and 2 more

Bilateral lung transplant for pulmonary hypertension with pulmonary artery aneurysmBerhane Worku MD1,2, Charles Mack MD1,3, Ivancarmine Gambardella MD1,2New York Presbyterian Weill Cornell Medical Center, New York NY 10021New York Presbyterian Brooklyn Methodist Hospital, Brooklyn NY 11215New York Presbyterian Queens Hospital, Queens NY 11335Corresponding AuthorBerhane Worku MD Brooklyn Methodist HospitalDepartment of Cardiothoracic Surgery506 6th StreetBrooklyn, NY 11215718-780-7700Bmw2002@med.cornell.eduPulmonary artery aneurysms (PAA) may be secondary to congenital cardiac defects such as a patent ductus arteriousus (PDA), atrial septal defect, or ventricular septal defect. They may also occur secondary to infection or connective tissue disease or they may be idiopathic in nature. Repair is undertaken to prevent the sequelae of rupture or dissection, although the specific size criteria at which repair is recommended remains controversial. Pulmonary hypertension (PH) may also lead to PAA, in which case isolated repair is not recommended. Heart-lung transplant has classically been the treatment of choice for PH with PAA, especially when associated with congenital heart defects, right ventricular dysfunction, and pulmonic valve regurgitation.In the setting of PH with PAA and correctable cardiac defects, bilateral lung transplant (BLT) has been described. Concurrent PAA repair is required, and several techniques exist to allow for this. In the current issue of the Journal of Cardiac Surgery, Doi et. al. offer a review of PH with PAA, with a focus on strategies to allow for BLT and PAA repair, hence avoiding the need for HLT. They describe a case of a patient with PH secondary to a PDA and a 9cm PAA who underwent BLT and PAA repair. The donor descending aorta and a bovine pericardial tube was used to reconstruct the recipient main and right PA, respectively. The patient suffered from persistently elevated PA pressures postoperatively due to a kink in the anastomosis between the neo-main PA (donor descending aorta) and the neo-right PA (bovine pericardial tube) requiring surgical revision, but the patient otherwise made an excellent recovery1.The benefit with BLT (rather than HLT) stems from limitations in donor supply which may result in unacceptably long wait times and reduced waitlist survival in patients awaiting HLT. As right ventricular function typically improves after BLT for PH, the donor heart from a HLT bloc may be better served to another patient with terminal cardiac failure. A variety of techniques have been described to allow for repair of massive PAAs at the time of BLT. Harvesting of the entire donor PA to allow replacement of the PAA has been described and is feasible when the donor heart is unsuitable for transplantation2,3. When the donor main PA is unavailable for harvesting, pulmonary arterioplasty and replacement with donor descending aorta have been described at the time of BLT4-7. After resection of the PAA, the proximal donor aorta is anastamosed to the proximal PA with the distal aorta oriented towards the right lung. The distal donor aorta is anastamosed to the donor right PA. The innominate and left carotid orifices can be used for anastomoses to the donor left PA5,6. Extension of a short donor left PA with an autologous pericardial tube has been described5. Similarly, extension of a short donor right PA with a bovine pericardial tube is described in the current report1.Pulmonary valve (PV) regurgitation may occur secondary to annular dilation from the PAA. PV replacement has been described, including sutureless valve implantation with valves intended for percutaneous deployment4. Durability remains a concern, and valve sparing repair techniques (commisuroplasty) have also been described3. When the donor heart is not being harvested, BLT with procurement of the donor right ventricular outflow graft has been described8. HLT always remains a reasonable option in the setting of extremely massive PAA associated with severe PV regurgitation and right ventricular dysfunction, assuming adequate donor availability and ability of the recipient to tolerate the longer wait time9.Recovery of right ventricular function and tricuspid regurgitation after BLT for PH has been documented, supporting the shift from HLT to BLT for this entity. In the setting of left ventricular diastolic dysfunction, severe pulmonary edema and hypoxia can be seen after BLT for PH as the LV is suddenly loaded, and in such a scenario ECMO has been utilized to allow time for LV remodeling. Various centers may prefer HLT over BLT for these cardiac consequences of prolonged PH10. In the absence of these complicating factors, BLT should be considered for PH in otherwise appropriate candidates. BLT for PH with PAA is likely best managed with harvesting the donor main PA when the donor heart is not being considered for harvest. When the donor PA is not available, the decision to attempt the abovementioned strategies for PAA repair such as neo-PA creation with donor aorta and the associated prolongation of donor ischemic time must be weighed against exposing the patient to elevated waitlist mortality while waiting for an acceptable heart-lung bloc to become available. Transplant center expertise and regional differences in heart and lung donor utilization rates will likely a relevant factor to consider when selecting the optimal strategy for each patient.REFERENCESDoi A, Gajera J, Niewodowski D, Gangahanumaiah S, Whitford H, Snell G, Kaye D, Joseph T, McGriffin D. Surgical management of giant pulmonary artery aneurysms in patients with severe pulmonary arterial hypertension. J Card Surg; in press]Schwarz S, Benazzo A, Prosch H, Jaksch P, Klepetko W, Hoetzenecker K. Lung transplantation for pulmonary hypertension with giant pulmonary artery aneurysm. J Thorac Cardiovasc Surg 2020;159:2543-50Shayan H, Sareyyupoglu B, Shigemura N, Thacker J, Bermudez C, Toyoda Y. Lung transplant, double valve repair, and pulmonary artery aneurysm resection. Ann Thorac Surg 2012;93:e3-5Pelenghi S, Primiceri C, Belliato M, Ghio S, Scelsi L, Totaro P. Is it time for a paradigm shift: Should double-lung transplant be considered the treatment of choice for idiopathic pulmonary arterial hypertension and giant pulmonary aneurysm? J Card Surg 2021;36:2996-2999Noda M, Okada Y, Saiki Y, Sado T, Hoshikawa Y, Endo C, Sakurada A, Maeda S, Oishi H, Kondo T. Reconstruction of pulmonary artery with donor aorta and autopericardium in lung transplantation. Ann Thorac Surg 2013;96:e17-9Force SD, Lau CL, Moazami N, Trulock EP, Patterson GA. Bilateral lung transplantation and pulmonary artery reconstruction in a patient with chronic obstructive pulmonary disease and a giant pulmonary artery aneurysm. J Thorac Cardiovasc Surg 2003;126:864-6.Oda H, Hamaji M, Motoyama H, Ikeda T, Minatoya K, Nakajima D, Chen-Yoshikawa TF, Date H. Use of a three-dimensional model in lung transplantation for a patient with giant pulmonary aneurysm. Ann Thorac Surg 2020;109:e183-5Zanotti G, Hartwig MG, Davis RD. A simplified technique for pulmonary artery aneurysm repair in a lung transplant recipient with right ventricular outflow tract obstruction. J Thorac Cardiovasc Surg 2013;145: 295-6Eadington T, Santhanakrishnan K, Venkateswaran. Heart-lung transplantation for idiopathic pulmonary arterial hypertension and giant pulmonary artery aneurysm – case report. J Cardiothorac Surg 2020;15:169Budev MM, Yun JJ. Advanced circulatory support and lung transplantation in pulmonary hypertension.
What is Different About Pulsed Field Ablation … Everything?David E. Haines, MDBeaumont Health System, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, USAFunding: NoneDisclosures: Dr. Haines is a consultant for Ablacon, Inc., Affera, Inc., Biosense Webster, Inc., Boston Scientific Corporation, Inc., Medtronic, Inc., and Philips Healthcare, Inc. He has equity interest in Ablacon, Inc. and Affera, Inc.Corresponding author:David E. Haines, MD Director, Heart Rhythm Center Professor, Cardiovascular Medicine Oakland University William Beaumont School of Medicine 3601 West 13 Mile Road Royal Oak, MI 48073 248-898-4176 dhaines@beaumont.eduFrom the time of early preclinical reports of the efficacy, speed and safety of pulsed field ablation (PFA), the interventional electrophysiology community has been waiting in anxious anticipation for its clinical approval and release. As most people actively engaged in interventional electrophysiology know, PFA is the technology that creates myocardial lesions with trains of very high voltage pulses that are nanoseconds or microseconds in duration.1 This form of ablation is nonthermal, and cell injury/death is created by electroporation of the organelles and sarcolemmal membrane, with cell death occurring via apoptosis as well as other mechanisms.2 Because myocardial ablation is the result of an electrical field effect, electrode-tissue proximity is important but contact force is not. The physiological effect of acute PFA is striking in that there is immediate loss of electrical signal so that acute pulmonary vein isolation is achieved from a single shot catheter in under one second (figure 1). Preclinical animal studies have demonstrated effective chronic lesions that have been reliably transmural for atrial ablations.3 But the most compelling aspect of PFA is the apparent tissue selectivity of this energy form. At doses sufficient to create reliable transmural lesions in animals, there is little or no discernable injury to the esophagus, phrenic nerves, coronary arteries or distal pulmonary veins, in contrast to ablation with thermal techniques such as radiofrequency or cryoballoon ablation, where thermal collateral injury to contiguous structures can lead to substantial morbidity and death.4,5So, what is the catch? Is there any downside to PFA compared to other ablation technologies? The answer is that we do not know. Despite a substantial body of preclinical experience published to date, clinical outcomes with PFA are just starting to be reported. In this issue of theJournal , Neven et al describe the acute pathological effects of PFA in a swine model over the first 60 minutes and compare them to findings from chronic animals at 3 weeks and 3 months.6 For their study, they mostly employed a suction electrode for epicardial delivery (some lesions created with a circular catheter under blood) and delivered a single unipolar cathodal pulse of mostly 200 J (some dose ranging performed with chronic lesions between 30 – 200 J) at various sites on the right and left ventricles. Pathology on acute specimens was examined 0 to 60 minutes post ablation, and chronic specimens were examined after 3 weeks and 3 months. They reported that acute lesions showed contraction band necrosis and interstitial edema, and at >/= 3 weeks, there was sharply demarcated connective tissue that evolved into scar.What new insights have we gained from the present study that we can now apply to the burgeoning field of clinical PFA? Unfortunately, despite considerable effort put forth by these investigators, their results are not generalizable to the wider field of PFA. No study reporting outcomes using one proprietary PFA system will be necessarily applicable to results from a competing proprietary system. The field of catheter ablation has become accustomed to interchangeability of one RF generator or catheter for another. That is because the thermodynamics of electrical resistive heating of tissue is predictable, and there are limited operator parameters (power, time, contact force) and design parameters (electrode size, convective cooling) that affect tissue heating. The biological effects of hyperthermia are straightforward and reproducible; thus, it is possible for scientists and clinicians to compare experiences from one proprietary RFA system to another and draw some generalizable conclusions. 7 Not so with PFA. To paraphrase an old saying, “When you’ve seen one PFA system, you’ve seenone PFA system.” The operator-controlled parameters are familiar (energy level, catheter-tissue position), but the design parameter variations are dizzying and most importantly unknown to us . A precedent was set early in the development of this field that the PFA waveform was proprietary, and that the commercialized product was a “black box”. A few of the parameters that can be modulated by the manufacturer include pulse amplitude, pulse duration, unipolar/bipolar, monophasic/biphasic, interpulse delay, interphase delay, pulse train number, pulse train duration and more. For example, the waveform used by Neven et al. was a milliseconds duration, monophasic damped sine wave generated by an external defibrillator (Lifepak 9, Physio-Control, Inc; Redmond, WA) and delivered in a unipolar cathodal fashion to an indifferent dispersive skin electrode. In contrast, most PFA systems deliver pulses are nanoseconds to microseconds in duration with a range of variation of the other parameters listed above (figure 2). Thus, the outcomes from ablation with a proprietary PFA system cannot and should not be extrapolated to different proprietary systems that may have dramatically different waveforms that result in different procedural outcomes.One of the major unanswered questions in the field of PFA is what is the time course of clinical effect after energy delivery? The hope and anticipation has been that lesions created by PFA will be more durable than those created with thermal ablation techniques (RFA or cryoablation). A dramatic features of catheter ablation with PFA is that disappearance of the local electrograms is seen immediately after pulse delivery (figure 1). Unfortunately, this does not necessarily indicate that a permanent lesion has been created. Beyond the border of irreversible electroporation there is a penumbra of reversible electroporation manifested by loss of the electrical signal but maintenance of viability. In the heart, this has been described pathologically as a rim of tissue with enhanced with hematoxylin and eosin staining, and maintenance of mitochondrial activity as delineated by cytochrome C oxidase staining.8 Thus, the acute end point of conduction block and loss of local electrogram signal employed in RF ablation does not indicate that a permanent lesion has been made with PFA. With myocardial ablation, the extent of reversible electroporation beyond the border of permanent injury has not been fully characterized, nor has the time course of recovery of normal function. There are many anecdotal reports of pulmonary vein reconnection after acute PVI with PFA in patients with atrial fibrillation. Unfortunately, the present study did not report mapping data and compare the extent of acute physiological effect to the acute pathological lesions.Therefore, a challenge for operators performing PFA is that acute electrogram voltage mapping cannot be used as a metric to assess therapeutic effect. The strategy adopted for PVI with PFA is to deliver a very large ablation dose, since injury to collateral structures is rare.9 The larger the energy delivery, the more likely it will be that permanent block is achieved. One experienced operator concluded “Go big or go home”. Once again, the pulse wave morphology, pulse width and pulse train number are proprietary features of the system that are preselected. The operator can choose different pulse amplitudes, but in almost all cases the maximum setting is selected. Is there such a thing as too much energy delivery with PFA? In preclinical studies, very high energy delivery has been associated with large volume microbubble production and evidence of thermal effects (charring) at the electrode-tissue interface. Creating a large uncontrolled lesion may be appropriate for a narrowly defined anatomical target like the pulmonary vein antrum but may not be appropriate for targeting other arrhythmogenic substrates because of concern about excessive injury to the surrounding myocardium. The consequences of very high PFA energy delivery in the clinical setting are unknown but most experts believe that there should be an upper safe limit established for each unique PFA system. So, the manufacturers will decide the dosing that the clinician will use. Will the recommended dose be safe and effective for all patients going forward? Time will tell. Ideally, we should have a method to assess myocardial viability after PFA prior to removing catheters from the heart, so that touch up ablations with improved catheter-tissue proximity can be performed. With RFA, promising technologies like real time magnetic resonance imaging,10 near field ultrasound imaging11 and NADH fluorescence12 have been explored, but their utility in assessing acute PFA lesions is unknown.The era of PFA is exciting and full of promise, but there are many unanswered questions that remain. As we gain more clinical experience with PFA, the benefits and limitations of the various commercial systems will become more obvious. Because of its speed and safety, PFA is likely to become the dominant mode of ablation for PVI, but we need to move forward in this field cautiously with recognition that all of the consequences of this ablation mode are still unknown.References:Verma A, Asivatham SJ, Deneke T, Castellvi Q, Neal RE. Primer on pulsed electrical field ablation: understanding the benefits and limitations. Circulation Arrhythm Electrophysiol. 2021; 14: e010086. TB, Polajzer T, Miklavcic D. Cell death due to electroporation – A review. Bioielectrochemistry. 2021; 141:107871.Stewart MT, Haines DE, Verma A, Kirchhof N, Barka N, Grassl E, Howard B. Intracardiac pulsed field ablation: Proof of feasibility in a chronic porcine model. Heart Rhythm. 2019; 16:754-764. doi: 10.1016/j.hrthm.2018.10.030.Bradley CJ, Haines DE. Pulsed field ablation for pulmonary vein isolation in the treatment of atrial fibrillation. J Cardiovasc Electrophysiol. 2020 Aug;31(8):2136-2147. doi: 10.1111/jce.14414.Koruth J.S., Kuroki K., Kawamura I., et. al.: Pulsed field ablation vs radiofrequency ablation: esophageal injury in a novel porcine model. Circ Arrhythm Electrophysiol 2020; 13:Neven K, van Driel VJHM, Vink A, du Pre BC, van Wessel H, Futing A, Doevendans PA, Wittkampf FHM, van Es R. Characteristics and time course of acute and chronic myocardial lesion formation after electroporation ablation in the porcine model. J Cardiovasc Electrophysiol. 2022 (in press).Haines DE. Biophysics and Pathophysiology of Radiofrequency Lesion Formation. In: Catheter Ablation of Cardiac Arrhythmias, 4th Edition. Huang SKS, Miller JM, editors. Philadelphia, PA: Elsevier Saunders Publishing, 2020.Nakagawa H, Castellvi, Neal R, Girouard S, Kuroda S, Hussein AA, Saliba WI, Wazni OM. Histological characterization of reversible and irreversible ventricular lesion boundaries produced by pulsed field ablation. Heart Rhythm 2021; 18: S151-S152. doi: 0.1016/j.hrthm.2021.06.386Reddy VY, Neuzil P, Koruth JS, Petru J, Funosako M, Cochet H, Sediva L, Chovanec M, Dukkipati SR, Jais P. Pulsed field ablation for pulmonary vein isolation in atrial fibrillation. J Am Coll Cardiol 2019; 74: pp. 315-326. doi: 10.1016/j.jacc.2019.04.021.Mukherjee RK, Roujol S, Chubb H, Harrison J, Williams S, Whitaker J, O’Neill L, Silberbauer J, Neji R, Schneider R, Pohl T, Lloyd T, O’Neill M, Razavi R. Epicardial electroanatomical mapping, radiofrequency ablation, and lesion imaging in the porcine left ventricle under real-time magnetic resonance imaging guidance-an in vivo feasibility study. Europace. 2018 Sep 1;20(FI2):f254-f262. doi: 10.1093/europace/eux341.Haines DE, Wright M, Harks E, Deladi S, Fokkenrood S, Brink R, Belt H, Kolen AF, Mihajlovic N, Zuo F, Rankin D, Stoffregen W, Cockayne D, Cefalu J. Near-Field Ultrasound Imaging During Radiofrequency Catheter Ablation: Tissue Thickness and Epicardial Wall Visualization and Assessment of Radiofrequency Ablation Lesion Formation and Depth. Circ Arrhythm Electrophysiol. 2017 Dec;10(12):e005295. doi: 10.1161/CIRCEP.117.005295.Swift L, Gil DA, Jaimes R 3rd, Kay M, Mercader M, Sarvazyan N. Visualization of epicardial cryoablation lesions using endogenous tissue fluorescence. Circ Arrhythm Electrophysiol. 2014 Oct;7(5):929-37. doi: 10.1161/CIRCEP.114.001750.Figures:Figure 1 – A circular ablation catheter is positioned in the right superior pulmonary vein antrum (PV 1 thorugh 9) and high frequency near field pulmonary vein potentials were recorded. Immediately after delivery of a PFA pulse, the pulmonary vein potentials are eliminated.Figure 2 – A. Irreversible electroporation waveform similar to that employed by Neven et al. from a Lifepak 9 defibrillator (Physio-control Service Manual No. 803763-06, Physio-control, Redmond, WA). B. Representative waveform from a pulsed field ablation generator using a train of biphasic microsecond duration pulses.

Michele Di Mauro

and 3 more

The meta-analysis by He and collaborators [has the worth to cover, as much as possible, a gap of scientific evidence where conducting a randomized trial appears very complex for ethical and logistical reasons. The authors concluded that mitral valve repair (MVP) provide better pooled results, both early and late, with respect to mitral valve replacement (MVR). However, the superiority of MVP is driven by some single large cohort-studies where surgeons had wide experience in the field of MVP for IE. This finding is also confirmed by other studies. But if mitral repair produces such a better short- and long-term survival than replacement, why are there no clear indications from consensus and guidelines pushing surgeons toward the pursuit of a reconstructive procedure at almost any cost? We wonder but to repair or not to repair, is that really the question? The AATS consensus suggests to repair “whenever possible” but without providing more specific indications. If the two primary goals of surgery are total removal of infected tissues and reconstruction of cardiac morphology, including repair or replacement of the affected valve(s), probably MVP as to perform in case of less extensive tissue detriment by the infection. In more wide valve involvement, MVP may be the choice but only in very expert hands and in Centers with very large volume of valve repairing. This decision cannot therefore be the result of the choice of an individual but must derive from a careful multidisciplinary discussion to be held in an EndoTeam.

Magali Lemaitre

and 9 more

Background: In France, each year, influenza viruses are responsible for seasonal epidemics leading to 2-6 million cases. Influenza can cause severe disease that may lead to hospitalization or death. As severe disease may be due to the virus itself or to disease complications, estimating the burden of severe influenza is complex. The present study aimed at estimating the epidemiological and economic burden of severe influenza in France during eight consecutive influenza seasons (2010-2018). Methods: Influenza-related hospitalization and mortality data and patient characteristics were taken from the French hospital information database, PMSI. An ecological approach using cyclic regression models integrating the incidence of influenza syndrome from the Sentinelles Network supplemented the PMSI data analysis in estimating excess hospitalization and mortality (CépiDc – 2010-2015) and medical costs. Results: Each season, the average number of influenza-related hospitalizations was 18,979 (range: 8,627-44,024), with an average length of stay of 8 days. The average number of respiratory hospitalizations indirectly related with influenza (i.e., influenza-associated) was 31,490 (95% CI: 24,542-39,012), with an average cost of \euro141 million (range: 54-217); 70% of these hospitalizations and 77% of their costs concerned individuals ≥ 65 years of age (65+). More than 90% of excess mortality was in 65+ subjects. Conclusions: The combination of two complementary approaches allowed estimation of both influenza-related and associated hospitalizations and deaths and their burden in France, showing the substantial impact of complications. The present study highlighted the major public health burden of influenza and its severe complications, especially in 65+ subjects.

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