Mini-commentary on BJOG-20-1459.R1: Caesarean birth and risk of subsequent preterm birth: retrospective cohort studyDeclarative title to be addedBradley de VriesSchool of Public HealthUniversity of SydneySydneyNew South WalesAustraliaWorldwide, preterm birth occurs in 11% of pregnancies and is the leading cause of childhood mortality. Complications from preterm birth are the most common cause of neonatal death in the United Kingdom, yet the incidence of preterm birth is not falling.In this issue of BJOG, Williams et al (BJOG xxxx) report on an observational study which identifies previous second stage caesarean birth as a risk factor for spontaneous preterm birth, confirming the results of other observational cohorts. Among women with one previous term birth, the adjusted odds ratio was 2.1 (95% confidence interval [CI] 1.3 to 3.1) for preterm birth before 37 weeks gestational age and 7.5 (95% CI 3.4 to 15) for preterm birth before 34 weeks, for previous second stage caesarean birth compared with previous vaginal birth. They adjusted for confounders not addressed in other studies including interpregnancy interval and maternal deprivation index, strengthening the existing evidence. The association is plausible because the cervix and lower uterine segment are anatomically merged in the second stage of labour and inadvertent cervical incision might damage the integrity of the cervix. The association was at least as strong as that described for previous excisional surgery for cervical dysplasia. Current National Institute of Clinical Excellence Guidelines recommend considering prophylactic cervical cerclage for an ultrasound-measured cervical length < 25mm if there is a history of cervical trauma. Given the plausibility and emerging epidemiological evidence, it would seem prudent to offer the same screening and treatment when there is a history of second stage caesarean birth.The observed association is relevant in other ways. Counselling about instrumental versus caesarean birth may be influenced by knowledge of future risks. Additionally, surgeons may need to be aware of the potential importance of avoiding inadvertent cervical incision, while still avoiding upper segment incision and its attendant risk of future intrapartum uterine rupture.The study by Williams et al is well designed, yet there remains potential for confounding not adjusted for in the analysis. Further, missing data for body mass index (1.6%) and cigarette smoking (13%) were classified as unknown and not imputed which can also cause bias. As there are only a handful of observational studies, it would be sensible to confirm the association, and explore potential causative mechanisms (e.g., by monitoring cervical length in subsequent pregnancies).Clinical prediction models for spontaneous preterm labour in asymptomatic women have been developed but need improvement before incorporation into clinical practice. Addition of new risk factors such as second stage caesarean birth and better understanding of the causes of preterm birth could improve these models and ultimately improve outcomes through offering prophylaxis with cervical cerclage, vaginal progesterone, or pessary for women at high risk.Given the massive personal, clinical, and economic burden imposed by preterm birth, the plausibility of the association, and the growing evidence from observational studies, I believe cervical surveillance warranted, with a view to offering prophylactic measures when there is a history of second stage caesarean birth.No disclosures: A completed disclosure of interest form is available to view online as supporting information.

Background The impact of physical activity during pregnancy and postpartum on urinary incontinence in women is unclear. Objectives To assess the association of physical activity and urinary incontinence during pregnancy and postpartum in a systematic review of the literature. Search Strategy A search of publications indexed in five major electronic databases (CENTRAL, PubMed, EMBASE, CINAHL and PEDro) was performed from their respective inception dates to the 30 March 2020 with a combination of keywords to identify studies of interest. Google Scholar was used for non-indexed literature. Selection Criteria All studies comparing physical activity with standard care in pregnant and postpartum women were selected. Data collection and Analysis Two reviewers, independently, selected studies, assessed quality and extracted data. Odds ratio with 95% confidence intervals were calculated using fixed effects or random effects meta-analyses (Mantel-Haenszel method), for low and moderate heterogeneity between studies, respectively. Main Results Seven studies (n = 12479) were included. Data of four studies could be pooled for meta-analyses; subgroup and sensitivity analyses were not possible. Physical activity, either during pregnancy or postpartum, is not associated with urinary incontinence, OR 0.90 (95% CI: 0.69–1.18) and OR 1.31 (95% CI: 0.74–2.34), respectively. Conclusions The ‘low’ quality of evidence (GRADE) does not show that physical activity during pregnancy or postpartum has any impact on urinary incontinence. Moderate physical activities should therefore be encouraged for the evidence-based benefits associated on other obstetrical outcomes. Funding None to declare. Keywords Pregnancy; postpartum; urinary incontinence; physical activity; exercise

The apoptotic signaling pathway is obviously disordered in systemic lupus erythematosus (SLE). Concurrent occurrence of induced apoptotic cell death and altered phagocytosis promotes autoantigen production, which leads to the biosynthesis of autoantibodies and autoimmune disorders. Natural IgM (nIgM) is important in clearing apoptotic cells and preventing them from triggering deleterious autoimmunity. B-1- and innate-like B- (ILBs) cells are the main nIgM producers. Human CD27+IgD+B cells (un-switched memory B cells) are considered ILBs. However, their functional properties in SLE remain undefined. Here, individuals with SLE showed markedly reduced CD27+IgD+B cell amounts. Moreover, these cells had altered function in terms of natural antibody-like IgM production. CD27+IgD+B cells also showed negative correlations with clinical and immunological properties in SLE patients. Following effective treatment achieving SLE remission, CD27+IgD+B cell amounts were restored. Jointly, these findings suggest that CD27+IgD+B cell dysfunction potentially contributes to the exacerbation of SLE, and modulating their features may represent a powerful tool for treating this persistent disease.

Both two-dimensional (2D) and three-dimensional (3D) echocardiography can be used in the early diagnosis of myocardial toxicity in patients with anthracycline chemotherapy. However, there are few studies on the detection of early myocardial damage in specific regions. This study compared the role and significance of 2D strain and 3D strain in discovering early segmental dysfunction. We prospectively studied 56 breast cancer patients who received anthracycline therapy. The mean age of patients was 47.6 ± 8.1 years. They all received 4-6 cycles of chemotherapy. Before chemotherapy and after every two cycles, patients underwent standard echo, 2D and 3D speckle-tracking echocardiography (STE) and real-time three-dimensional echocardiography (RT-3DE). Compared with the baseline value (T0), 3D GLS was significantly reduced after two cycles (T2) (P<0.05), after four cycles (T4) 3D GCS was significantly reduced (P<0.05), after six cycles (T6) 2D derived EF, 2D GLS, E/e’ ratio, Fractional shortening (FS), 3D derived EF, 3D GAS, GRS were considerably decreased (P<0.05). The area supplying blood from the anterior descending branch of the left coronary artery was the most susceptible to chemotherapy, and 3D GLS was found earlier than 2D GLS which was decreased considerably after two cycles (P<0.05). In anthracycline chemotherapy patients, some regions of early myocardial dysfunction may be more easily involved, through the evaluation of 2D and 3D echocardiography, 3D speckle tracking echocardiography may be more able to identify the involved segments of myocardium early. Moreover, the apical segments of the left ventricle seem to be more susceptible to cardiotoxicity.

The care of patients with vascular anomalies is quickly becoming a complex field requiring high quality, coordinated multidisciplinary care. In this article, we review the history of multidisciplinary care in this field, discuss the benefits of this model of care, and outline some of the essential components and structure of a successful vascular anomalies team. We provide an overview of two example programs and a roadmap for other centers to develop their own multidisciplinary vascular anomalies teams.

A document by Denise Adams, written on Authorea.

Background: Invasive fungal diseases (IFD) are important causes of mortality in children with cancer. We aimed to determine the extent of survival in patients treated for IFD in the last nine years at our center. Procedure: a retrospective cohort of patients treated from January 1, 2011 to December 31, 2019. Weibull distribution was used to parameterize hazard ratios and accelerated failure time models, for the outcome “death attributed to IFD”. Results: We analyzed 152 patients with IFD (133 proven and 19 probable), with median age of 97 months. The most frequent diagnoses were leukemia (39, 25.7%) and central nervous system tumors (36, 23.7%). Thirty-seven patients received prophylaxis with fluconazole (24.3%). There were 133 fungi isolates, and most frequent were Candida species in blood (84, 55.2%). Forty-three deaths were attributed to IFD (28.3%). Survival probabilities were lower for pulmonary IFD (46.9%, p = 0.0017), leukemia (62.5%, p = 0.004), and neutropenia <500 cells/mm3 (55.4%, p < 0.0001). For Candida fungemia, survival probabilities were 76.6% (p = 0.043). In Weibull models, diagnosis of leukemia shortened survival times by a factor of 0.006, relapse of disease by 0.05, lymphoma by 0.04, pulmonary IFD by 0.04, and neutropenia by 0.015. Hematopoietic stem cell transplantation did not affect the survival times, as well as prophylaxis with fluconazole. Conclusions: Host factors, like neutropenia, relapse of disease and hematologic malignancies, are determinant in the survival times of children with IFD, as well as pulmonary involvement. Fluconazole prophylaxis and HSCT do not affect the hazards of death.

Background Symptom-focused management is one of the cornerstones of optimal atrial fibrillation (AF) therapy. Objectives To evaluate the use of rhythm control and rate control strategy. Second, to identify predictors of the use of amiodarone in patients with rhythm control and of the use of rhythm control strategy in patients with paroxysmal AF in the Balkans. Methods Prospective enrolment of consecutive patients from 7 Balkan countries to the BALKAN-AF survey was performed. Results Of 2,712 enrolled patients, 2,522 (93.0%) with complete data were included: 1,622 (64.3%) patients were assigned to rate control strategy and 900 (35.7%) to rhythm control. Patients with rhythm control were younger, more often hospitalized for AF and with less comorbidities (all p <0.05) than those with rate control. Symptom score [European Heart Rhythm Association (EHRA)] was not an independent predictor of a rhythm control strategy [odds ratio (OR) 0.99, 95% confidence interval (CI) 0.90-1.10, p = 0.945]. The most commonly chosen antiarrhythmic agents were amiodarone (49.7%), followed by propafenone (24.3%). Conclusion More than one third of patients in BALKAN-AF survey received a rhythm control strategy, and these patients tended to be younger with less comorbidities than those managed with rate control. EHRA symptom score is not significantly associated with rhythm control strategy. The most commonly used antiarrhythmic agents were amiodarone, followed by propafenone.

Introduction: The factorial analysis of different variables like length of stay, the overall cost of the treatment, cost of medical supplies and equipment, cost of diagnostic tests, cost of the drug, lipid profile, glycaemic profile, and hypertensive profile investigations on admission is performed. Methods: In a prospective observational study, all the patients who referred to the medicine department of the three different hospitals located in Moga, City Punjab, and those who were hospitalized due to diabetes mellitus (type-I and type-II with co-existing hypertension were asked to participate in the study. Results: The patients’ mean age was found to be M = [53.85], SD = [11.54] years. Out of 1914 patients, 914 were male (47.8%), followed by female 1000 (53.65%). The factorability of the 16 items was examined. It was observed that 14 variables are loaded onto Factor 1. It was found that 14 variables all relate to the length of stay, cost of treatment, and other lab investigations vice versa. Three variables, BPD, FBS, RBS, load onto a second factor related to each other. Discussion: This study explored the positive correlation between blood glucose profile fasting blood sugar, random blood sugar, and HbA1c, with systolic blood pressure, diastolic blood pressure. The patients’ lipid profile includes cholesterol level of the patients, low-density lipoproteins, triglycerides, very-low-density lipoproteins with a length of stay, cost of drugs used, cost of the diagnostic test, and medical supplies of the patients. Conclusion: The factorial analysis revealed that length of hospital stay is positively correlated with overall all cost of the treatment, CMS: Cost of medical supplies and equipment’s (INR), CT: Cost of diagnostic tests (INR), CHO, LDL, TG, VLDL creatinine level, BPS, BPD, FBS, RBS and HbA1c of the patients except CD: Cost of the drug (INR).

In this paper, a new algorithm is considered to find a common element of the solution set of a pseudomonotone equilibrium problem and the fixed point set for a quasi-nonexpansive mapping in a real Hilbert space. The algorithm is based on the subgradient extragradient method, the inertial method and the viscosity method. The adaptive step size ensures that the algorithm does not need to know apriori the Lipschitz constants of the associated bifunction. Under standard assumptions, the strong convergence of the proposed algorithm was studied . Moreover, numerical experiments on several specific problems and comparison with other algorithms show the superiority of the algorithm.

Abstract：In the 1960 of the 20th century, scientists firstly advanced the concept of using gene therapy to cure the human genetic disease, which aimed to carry out precisely site-specific modification on the genome for obtain long-term therapeutic effect in patients. In the next 50 years, scientists have developed many new gene editing technologies including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR), etc. These new technologies have brought milestone breakthroughs in gene therapy era. In this review, we focus on how flexible the CRISPR system used in human genetic disease-focused research, gene therapy strategies, clinical trials and discuss some of the major challenges and significant benefit for its future use in patients.

Background Primary effusion lymphoma (PEL) is a rare disease occurs mostly in immunosuppressed young males. Treatment consists of chemotherapy and prognosis is poor. Case presentation Our case described immunocompetent elderly woman with PEL who survive 30 months without chemotherapy. Conclusion Physicians should be aware of all clinical scenarios of PEL

Treatment of ST represents a challenge. The presence of large amounts of thrombus combined with stent optimization increase the risk of distal embolization. A two-step strategy of stent implantation and deferred stent optimization might be appropriated. We hereby present three clinical cases of ST successfully treated with a two-step approach.

The study was carried out to determine the levels of awareness and knowledge of physicians about rare diseases in Turkey. The study included 390 physicians selected with the convenience sampling method. A questionnaire form, which was prepared by the researchers based on a literature review, was used as the data collection tool. The first section of the questionnaire includes questions about sociodemographic characteristics while the second section includes questions to determine the level of awareness and knowledge about rare diseases. The participants’ mean level of knowledge about rare diseases was 4.78±1.89 in this study. 75.7% of the participants encountered an individual with a rare disease, 69.2% did not know the prevalence used to define the rare diseases in EU countries and 67.6% did not know the prevalence used to define the rare diseases in Turkey. As the sources of information on rare diseases, 28% stated hospital practices, 26% stated extracurricular subjects and 25% stated core curriculum practices in medical education. The participants hold the pharmaceutical companies, government and physicians responsible for the development of drugs that can be used in the treatment of the rare diseases. This study reveals that the awareness and knowledge levels of physicians about rare diseases are low. In order to increase the awareness of doctors about rare diseases, it may be recommended to provide information about rare diseases during medical education.

Connectivity of marine populations is shaped by complex interactions of biological and physical processes across the seascape. The influence of environmental features on the genetic structure of populations has key implications to the dynamics and persistence of populations, and an understanding of spatial scales and patterns of connectivity is crucial for management and conservation. This study employed a seascape genetics approach combining larval dispersal modeling and population genomic analysis based on RADseq to examine environmental factors influencing patterns of genetic structure and connectivity for a highly-dispersive mud crab, Scylla olivacea (Herbst, 1796) in the Sulu Sea. Dispersal simulations reveal widespread but asymmetric larval dispersal influenced by persistent southward and westward surface circulation features in the Sulu Sea. Despite potential for widespread dispersal, significant genetic differentiation was detected among eight Sulu Sea populations based on 1,655 single-nucleotide polymorphism (SNP) markers (FST = 0.0057, p = 0.001) and a subset of 1,643 putatively neutral SNP markers (FST = 0.0042, p = 0.001). Oceanography influences genetic structure, as redundancy analysis (RDA) revealed significant contribution of asymmetric ocean currents to neutral genetic variation (R2adj = 0.133; p = 0.035). Genetic structure may also reflect demographic factors, with divergent populations characterized by low effective population sizes (Ne < 50). Pronounced latitudinal genetic structure was recovered for loci putatively under selection (FST = 0.2390, p = 0.001), significantly correlated with variability in mean sea surface temperatures during peak spawning months of S. olivacea (R2adj = 0.763; p = 0.041), suggesting putative signatures of selection and local adaptation of early life history stages to thermal clines. This study contributes to the growing body of literature documenting population genetic structure and local adaptation for highly-dispersive marine species, and provides information useful for spatial management of the fishery resource.

Introduction: We sought to investigate the net effect of wide area circumferential radiofrequency catheter ablation (WACA) on the atrial (LA) geometry. Methods and results: Seventy-one patients, who underwent a second PVI procedure, after index procedure of point-by-point WACA, for recurrent paroxysmal (n=31) or persistent (n=40) atrial fibrillation (AF) in our center were included. A three-dimension rotational angiography of the left atrium (3D-RA) under rapid ventricular pacing was performed immediately before ablation, at index and repeat ablation in all patients. LA geometry in terms of volume, sphericity and surface were assessed in all patients between first and second PVI. There was a statistical significant reduction of the LA volume (65,6 ± 14 ml/m2 vs 62,2 ± 15 ml/m2, p<0,001) and of the surface of the LA (74,4 ± 11,2 vs 70,4 ± 11,2 cm2/m2, p<0,001), whereas the sphericity of the LA increased significantly (82 ± 2% vs. 83 ± 2%, p=0,004) in all 71 patients. Patients with paroxysmal AF showed significant decrease of the LA volume (121,8 ± 25,7 vs 116 ± 32 ml, p=0,008) and increase of the LA sphericity (82,3 ± 2,1 vs 83,1 ± 2%, p=0,009). Patients with persistent AF showed significant decrease of the LA volume (133,5 ± 32 vs 126 ± 32 ml, p=0,005), but only a trend towards increased sphericity (82,4 ± 2,8 vs 83 ± 2,4%, p=ns). Conlusions: WACA results into significant reduction of the LA volume, LA surface area and into significant increase of the LA sphericity in treated patients with recurrent AF.

EP Rounds

Background The ablation index (AI) has been reported to be useful for a durable pulmonary vein isolation (PVI) to treat atrial fibrillation (AF). No study has reported the optimal AI value for the SVC isolation (SVCI). In this study, we aimed to investigate the optimal AI for the SVCI. Methods Thirty-six AF patients who underwent an initial SVCI were enrolled. Ablation was performed at a total of 549 points. The sites where dormant conduction was induced or additional ablation was needed were defined as touch-up sites (n=36). We compared the energy deliver time, power, CF, Force-Time Integral (FTI), and AI between the touch up sites and control sites (n=513). Results The median RF delivery time, power, CF, and FTI were all significantly lower at the touch up sites (touch up sites vs. control sites; energy delivery time, sec, 20.3[12.3-21.7] vs. 21.6[19.8-25.2], p=0.0003; power, W, 23.5[15-24] vs. 24[20-25], p<0.0001; CF, g, 7[6-10.8] vs. 11[9-15], p<0.0001; FTI, 126.5[99.3-208.8] vs. 244[183.5-340.5], p<0.0001). The AI also was significantly lower at the Touch up sites (touch up sites vs. control sites; AI, 350.1±43.6 vs. 277.2±21.8, p<0.0001). The median value of the AI at the control sites was 350 and no reconnections were seen where the minimum AI value was more than 308. Conclusion The AI value at the touch up sites was significantly lower than that at the control sites. The optimal AI value for the SVCI should be 350, and at least 308 would be needed.

As the largest tributary of the Shiyang River, with the average annual inflow of total runoff accounting for 23%, the Xiying River has representative of mountain runoff of inland rivers in the Northwest of China. Using samples collected in the Xiying River basin from September 2016 to October 2017, the water chemical composition and ion source characteristics of river was studied. The results show that the river is weakly alkaline, the average values of pH is 8.01 and the TDS is 179.29 mg·L-1. With the elevation decreasing along the river, the values of TDS of main stream tend to increase firstly and then decrease, but those of TDS of each tributary decrease, and latter is lower than the former. Affected significantly by the flow, the lowest value of ion concentration in river occurs in summer, and the highest value of it occurs in autumn and winter. The hydrochemical type of river is CaMg-HCO3. In the river, the order of cation mass concentration is NH4+

Catheter ablation using radiofrequency (RF) energy has been widely used to treat patients with atrial fibrillation (AF). The optimal levels of power and duration to increase the success rate while minimizing complications have not been fully established. Different centers continue to use various power protocols for catheter ablation of AF. Herein, we present a comprehensive review of the impact of power output on efficacy and safety of RF ablation for AF. High power short duration (HPSD) ablation can be performed safely with similar procedural efficacy as low power long duration (LPLD) ablation strategy. HPSD ablation has the potential to shorten procedural and RF times and create more durable and localized lesions.

Abstract: A 5-year-old male child with asymptomatic Wolff-Parkinson-White syndrome, cardiac dysfunction and dilated cardiomyopathy was reported. Electrophysiological study revealed a manifest accessory pathway on the right free wall. Heart failure and ventricular remodeling recovered after a successful radiofrequency ablation in the 10-11 o’clock of the tricuspid annulus. Conclusion: The dyssynchronous movement of the ventricular septum and left ventricular caused by right accessary pathway may be the main electrophysiological mechanism and the prognosis is good after blocking the conduction of accessary pathway.

Aims: Intravenous ATP may induce atrial fibrillation (AF). ATP shares similar receptor-effector coupling systems with acetylcholine. However, the association between an ATP injection and the hyperactivity of the intrinsic cardiac autonomic nervous system, known as ganglionated plexi (GPs), are not well-understood. We described a series of patients with non-pulmonary vein (PV) trigger sites provoked by an ATP injection, and assessed the feasibility of a ganglionated plexus (GP) ablation. Methods: Five hundred and ninety-nine consecutive patients (69% men; mean age, 68 ± years, 60% paroxysmal AF) were retrospectively examined. A total of 7 patients (1.2%) that had ATP-induced AF following a PV isolation were enrolled in this analysis. Results: The distribution of the foci overlapped the GP location; the coronary sinus (CS) in six patients, right atrial posterior wall (RAPW) adjacent to the interatrial groove in 2, mitral annulus in 2, ligament of Marshall in 1, right septum below the foramen ovale in 1 and left atrial posterior wall in 1, respectively. Among those trigger foci, we confirmed a vagal response by high frequency stimulation in the CS and RAPW in six and two patients, respectively. After a median RF time of 2.9 minutes (range 2.5 to 11.3) targeting those foci, six patients who received a repeat ATP injection became non-inducible. Conclusion: ATP-induced AF after a PV/Box isolation was associated with hyperactivity of atrial GP. The GP ablation was effective in this rare, but challenging situation.

Underrecognized consequence of three-dimensional mapping tool selection for atrial fibrillation ablation: when the operators’ decision determines the amount of silent micro-embolic burden Thomas Rostock MD, Torsten Konrad MD, Raphael Spittler MDFrom the University Hospital Mainz, Center for Cardiology,Cardiology II / Electrophysiology, Mainz, GermanyWord count: 1460Funding: (None)Disclosures: (None)

We investigated the soil physicochemical property and arbuscular mycorrhizal fungi (AMF) resilience to degradation and deforestation of the Chilimo dry evergreen Afromontane forest. Topsoil (1-10cm) physicochemical property was determined across four land uses, viz. natural forest (NF), shrubland (ShL), cropland (CrL), and grazing land (GrL). AMF spore abundance (SA) and AMF infectivity of these land uses were also determined. One-way ANOVA results indicated that most soil physicochemical variables were significantly affected by land-use change. According to the nonmetric multidiamentiaonal scaling ordination result, soil physicochemical property was found to be resilient to degradation (NF-ShL conversation) but not deforestation (NF-CrL or NF-GrL conversions) of Chilimo forest. Whereas SA was found to be resilient to both the degradation and deforestation, infectivity was resilient only to NF-CrL conversion. Although our results did not show a similar pattern in soil property, SA and AMF infectivity resilience due to Chilimo forest degradation and deforestation, both the soil physicochemical property and AMF infectivity were found to be not resilient to NF conversion to GrL. Hence, based on our results, it can be concluded that AMF inoculation could be more beneficial to NF restoration if the planting sites are in GrL. However, in the future, the AMF community composition of these four land uses should be determined morphologically and molecularly from field soil and trap culture so that AMF resilience to DAF deforestation and degradation is better understood.