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Tanya Djanogly

and 3 more

Objective To explore how women undergoing episiotomy experience and perceive the consent process. Design Qualitative interview study. Setting A postnatal ward in a London teaching hospital. Sample 15 women who had recently undergone episiotomy. Methods Semi-structured, audio-recorded interviews were analysed using thematic analysis. Main outcome measures Themes derived from analysis of interview transcripts. Results Three themes emerged in relation to women’s experiences of the episiotomy consent process: 1) realities of episiotomy practice, 2) information provision and 3) voluntariness of consent. Practical realities such as time pressure, concern for the baby’s health and women’s state of exhaustion, constrained consent discussions. Minimal information on episiotomy was shared with participants, particularly concerning risks and alternatives. Participants consequently inferred that there was no other choice to episiotomy. Whilst some women were still happy to agree, others perceived the consent process to be illusory and disempowering, and subsequently experienced episiotomy as a distressing event. Conclusions Consent to episiotomy is not consistently informed and voluntary and more often takes the form of compliance. Information must be provided to women in a timelier fashion in order to fulfil legal requirements, and to facilitate a sense of genuine choice. Funding The study has not received grant funding. The research team are funded by the Higher Education Funding Council for England (HEFCE). Keywords Episiotomy, consent, women’s experiences, qualitative

Wenwen Hu

and 5 more

Background: The use of extracorporeal membrane oxygenation (ECMO) to support critically ill patients with cardiorespiratory dysfunction is increasing over the last decades. However, hemorrhagic complications remain occurring frequently during ECMO support, which have a significant impact on morbidity and mortality. Methods: A retrospective study was performed on the 60 patients, who were admitted to the Taihe hospital in Shiyan City, Hubei Province from February 2017 to October 2020. All those were rescued with ECMO. Including 18 patients developed hemorrhage complications and 42 patients did not. Demographic, laboratory tests, clinical manifestations prior to ECMO were collected to analysis the clinical features. Univariable and multivariable logistic analysis methods were used in our study to explore the risk factors for hemorrhage in adults on ECMO. Results: There were significant differences between the hemorrhage group and no-hemorrhage group in duration of ECMO support, mode of ECMO, red blood cell count, hemoglobin, platelet count, serum creatinine. Particularly, multivariate logistic analysis showed that the longer duration of ECMO support and the higher activated partial thromboplastin time (APTT) prior to ECMO were independent factors for hemorrhage in adults on ECMO. In addition, we found that the mortality of hemorrhagic patients was higher than no-hemorrhagic patients. Cannula site was the most common bleeding site. Most bleeding events occurred within the first three days of ECMO therapy. Conclusions: Clinicians should evaluate the risk of hemorrhage based on patients’ coagulation function, underlying disease as well as the duration of ECMO support. Especially in the first three days during ECMO support. Attempting to wean from ECMO early whenever feasible is also effective to reduce the occurrence of hemorrhage. Special attention should be given on cannula site, mucosal, dermal and digestive tract to alert hemorrhage.

Jessica Yun

and 5 more

Background and Purpose Hepatocellular carcinoma (HCC) is the second most common cancer worldwide, demonstrating aggressiveness and mortality more frequently in men than in women. Despite reports regarding the inhibitory ability of estrogen receptor alpha (ERα, ESR1) in certain cancer progression, targets and the basis of underlying gender disparity in HCC worsening remain elusive. Experimental Approach Human HCC samples were used for immunoblottings and immunohistochemistry. Estradiol (E2) was treated to HCC cell lines and were evaluated by immunoblottings, polymerase chain reaction, immunofluorescence, and live imaging. Key Results Here, we report the ability of ERα to transcriptionally inhibit G protein subunit alpha 12 (Gα12). First, using human samples and public database, the expression of ERα and Gα12 in HCC was examined. Then, quantitative real-time PCR, chromatin immunoprecipitation-assay, luciferase assay, and immunoblottings confirmed the inhibitory ability of ERα on Gα12 and EMT. Additionally, we found microRNA-141 and -200a as downstream targets of the Gα12 signaling axis for cancer malignancy regulation under the control of ERα. As for in-depth mechanism, PTP4A1 was found to be directly inhibited by microRNA-141 and -200a. Gα12 and PTP4A1 promoted epithelial-mesenchymal transition, as well as mesenchymal to amoeboidal transition, antagonized by ERα modulations. Conclusion and Implications The identified targets and ESR1 levels inversely correlated in human specimens, as well as with sex-biased survival rates of HCC patients. Collectively, ERα-dependent repression of Gα12 and consequent changes in the Gα12 signaling may explain the gender disparity in HCC, providing pharmacological clues for the control of metastatic HCC.

Su Il Kim

and 6 more

Objectives: This study evaluated the characteristics of reflux in patients with laryngopharyngeal reflux (LPR) refractory to proton pump inhibitor (PPI) therapy using the 24-h multichannel intraluminal impedance (MII)-pH monitoring. Design: Prospective cohort study. Setting: A tertiary care otolaryngology clinic. Participants: Patients with suspected LPR underwent 24-hour MII-pH monitoring and were prescribed high-dose PPI twice daily. One-hundred and eight patients followed up for at least 2 months were enrolled. Main outcome measures: Patients with suspected LPR showing more than one proximal reflux episode were considered to have LPR. Patients with LPR showing ≥50% decrease in the follow-up reflux symptom index (RSI) score compared to the pre-treatment RSI score during treatment periods were defined as responders; others were defined as non-responders. Various parameters in the 24-h MII-pH monitoring between non-responders and responders with LPR were compared using Student’s t-test. Results: Of 108 patients with suspected LPR, 80 were diagnosed with LPR. Patients with LPR were categorized as non-responders (n = 19) and responders (n = 61). Proximal all reflux time and proximal longest reflux time in MII parameters were significantly higher in responders than in non-responders (p = 0.0040 and 0.0216, respectively). The proximal all reflux time >0.000517% was a better cut-off value to predict responders with LPR compared to the proximal longest reflux time >0.61 min (sensitivity + specificity: 1.317 vs. 1.291). Conclusions: The proximal all reflux time can be helpful to predict the response to PPI therapy and establish a personalized therapeutic scheme in patients with LPR.

Mohamed Fouda

and 1 more

Background and purpose. Cardiovascular anomalies are predisposing factors for diabetes-induced morbidity and mortality. Recently, we showed that high glucose induces changes in the biophysical properties of Nav1.5 that could be strongly correlated to diabetes-induced arrhythmia. However, the mechanisms underlying hyperglycemia-induced inflammation, and how inflammation provokes cardiac arrhythmia, are not well understood. We hypothesized that inflammation could mediate the high glucose-induced biophyscial changes on Nav1.5 through protein phosphorylation by protein kinases A and C. We also hypothesized that this signaling pathway is, at least partly, involved in the cardiprotective effects of CBD and E2. Experimental approach. To test these ideas, we used Chinese hamster ovarian (CHO) cells transiently co-transfected with cDNA encoding human Nav1.5 α-subunit under control, a cocktail of inflammatory mediators or 100 mM glucose conditions (for 24 hours). We used electrophysiological experiments and action potential modelling. Key Results. Inflammatory mediators, similar to 100 mM glucose, right shifted the voltage dependence of conductance and steady state fast inactivation and increased persistent current leading to computational prolongation of action potential (hyperexcitability) which could result in long QT3 arrhythmia. In addition, activators of PK-A or PK-C replicated the inflammation-induced gating changes of Nav1.5. Inhibitors of PK-A or PK-C, CBD or E2 mitigated all the potentially deleterious effects provoked by high glucose/inflammation. Conclusions and implications. These findings suggest that PK-A and PK-C may mediate the anti-inflammatory effects of CBD and E2 against high glucose-induced arrhythmia. CBD, via Nav1.5, may be a cardioprotective therapeutic approach in diabetic postmenopausal population.

Rassim Khelifa

and 3 more

Ashish Srivastava

and 10 more

Peiguo Yuan

and 2 more

Eryi Wang

and 10 more

Background: We have previously demonstrated that benzo(a)pyrene (BaP) co-exposure with dermatophagoides group 1 allergen (Der f 1) can potentiate Der f 1-induced airway inflammation. We sought to investigate the molecular mechanisms underlying the potentiation of BaP exposure on Der f 1-induced airway inflammation. Methods: BaP co-exposure with Der f 1-induced activation of TGFβ1 signaling was analyzed in airway epithelial cells (HBECs) and in asthma mouse model. The role of aryl hydrocarbon receptor (AhR) and RhoA in BaP co-exposure-induced TGFβ1 signaling was investigated. AhR binding sites in RhoA were predicted and experimentally confirmed by luciferase reporter assays. The role of RhoA in BaP co-exposure-induced airway hyper-responsiveness (AHR) and allergic inflammation was examined. Results: BaP co-exposure potentiates Der f 1-induced TGFβ1 signaling activation in HBECs and in the airways of asthma mouse model. The BaP co-exposure-induced the activation of TGFβ1 signaling was attenuated by either AhR antagonist CH223191 or AhR knockdown in HBECs. Furthermore, AhR knockdown led to the reduction of BaP co-exposure-induced active RhoA. Inhibition of RhoA signaling with fasudil, a RhoA/ROCK inhibitor, suppressed BaP co-exposure-induced TGFβ1 signaling activation. This was further confirmed in HBECs expressing constitutively active RhoA (RhoA-L63) or dominant negative RhoA (RhoA-N19). Luciferase reporter assays showed prominently increased promoter activities for the AhR binding sites in the promoter region of RhoA. Inhibition of RhoA suppressed co-exposure-induced AHR, Th2-associated airway inflammation and TGFβ1 signaling activation in asthma. Conclusions: Our studies identified a functional axis of AhR-RhoA that regulates TGFβ1 signaling activation, leading to allergic airway inflammation and asthma.

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The sinoatrial node in medication-resistant inappropriate sinus tachycardia: to modify or to ablate?Khalil El Gharib1*1Hôtel-Dieu de France, Beirut, Lebanon*Author for correspondence: khalil.gharib@outlook.comKEYWORDS: IST, sinus node modification, sinus node ablation, radiofrequency ablation, surgical ablationNo conflict of interest to discloseFunding: noneInappropriate sinus tachycardia (IST) is defined as a resting heart rate >100 beats per minute (with a mean heart rate >90 beats per minute over 24 hours) associated with highly symptomatic palpitations(1). The syndrome is associated neither with structural heart disease nor with any secondary cause of sinus tachycardia(2) and evidence suggests that enhanced intrinsic automaticity of the sinoatrial node, which can be due to anti-β-adrenergic antibodies, is behind its genesis(3). However, it is benign in terms of clinical outcomes and echocardiographic evidence of ventricular dysfunction(4), being rarely associated with tachycardia-induced cardiomyopathy(3).Patients with IST are essentially treated with ß-blockers to alleviate their symptoms(5). Ivabradine, a drug that inhibits funny calcium channels, particularly abundant in the SA node, showed modest benefit, receiving class IIa recommen­dation in the treatment of IST(4). But, the duration of medical therapy might be indefinite, and, a considerable number of patients would respond inadequately, or have no response, even after prolonged therapy(5). Historically, such patients would have subtotal right atrial excision, atrioventricular junctional ablation with permanent pacemaker implantation, or chemical occlusion of the sinus node artery(6). These options are considered today unacceptable in this setting, and other therapeutic approaches should be unveiled when resistance to medical treatment appears.Electrophysiological study was initially purely diagnostic, but recent advances in technology have allowed us to intervene(7); patients with ventricular and supraventricular tachyarrhythmias are successfully treated with percutaneous catheter procedures. Of these, SA node ablation/ modification has been proposed as alternative approaches in IST that is not responding to medical treatment; trials reported auspicious results, highlighted here.Electrophysiologic mapping to the site of the earliest endocardial activation during either spontaneous sinus tachycardia or isoproterenol-induced sinus tachycardia has rendered these procedures feasible(8). Additionally, combination with intracardiac echocardiography permitted a more accurate electrophysiologic and anatomic localization of the sinoatrial node(9).Sinus node modification is not a focal ablation, but requires complete abolition of the cranial portion of the SA node complex, the one that exhibits the most of the autonomic activity(9). It is defined as successful when the heart rate decreases by 30 beats per minute (bpm) during isoproterenol infusion(8). Short-term success was also defined by other investigators when there was a reduction of the baseline sinus rate to less than 90 bpm and the sinus rate during isoproterenol infusion by more than 20% or by 25%(8). The acute success rate for modification has been varying between 76 and 100 % across trials, while long-term clinical outcomes are modest at best, with reported freedom from IST ranging from 23 to 85%(10).Complications specific to SA node modification include superior vena cava (SVC) syndrome, diaphragmatic paralysis, and sinus node dysfunction(10). And while modification with conventional methods has its setbacks, modification using laser energy can be considered in the setting of IST. This modality creates clear-cut homogenous transmural lesions of the myocardium that comprises the scattered “functional” SA node(11). The burnt myocardium will then heal into a dense fibrous scar, decreasing potential amplitudes. And when adapting laser energy settings to the thickness of the myocardial wall, collateral dam­ages such as esophageal fistulae, lung burns, and phrenic nerve palsy will be avoided(11); thus, this technique may prove itself as a new intriguing alternative for the safe and effective treatment of IST.SA node modification is apt in achieving acute reductions in postprocedural heart rate. However, and as aforementioned, success rates are suboptimal in terms of symptomatic control with a significant recurrence rate(12). Catheter ablation aiming at either total exclusion and obliteration of the SA node has been described and performed, success being defined as a slowing of >50% from the baseline rate of tachycardia along with a junctional escape rhythm(12). With radiofrequency (RF) applications, the earliest local atrial activation time would shift from a cranial location to a more caudal one, usually at the mid-lateral right atrium(5). Reviews have reported that acute success rates were consistently to be as high as 88.9%, with an overall frequency of recurrence of 19.6%, the latter occurring within a wide range of post-ablation intervals, anywhere from a few weeks to several months after the procedure(12). Additionally, Takemoto and colleagues documented a significant drop in B-type natriuretic peptide levels, 6 to 12 months after ablation, suggesting fewer stretching shears on cardiac muscle.Two types of response of the sinus tachycardia to RFA were observed across studies, whether a step-wise reduction in sinus rate accompanying migration of the site of earliest atrial activation in a cranial-caudal direction along the lateral right atrial wall, or an abrupt drop in heart rate in response to RFA at a focal site of earliest atrial activation(13).However, RFA of inappropriate sinus tachycardia requires a large number of applications of radiofrequency energy and is, as in SA node modification, associated with a high recurrence rate(13). Complete remission is achieved only in approximately 50% of patients in some studies(14); longer history of IST and those reporting near syncope/syncope having a higher probability of recurrence(15).While other studies have shown that RF ablation of the SA node can achieve even longer-term reductions in the sinus rate and relief of symptoms in two-thirds of patients with drug-refractory, inappropriate sinus tachycardia(13), aiming specific sites related to the SA node should be elaborated, for better and optimal outcomes Killu and colleagues created a lesion in the arcuate ridge resulting in complete abolition of the tachycardia, since arrhythmias arising in this region may exhibit both electrocardiographic and clinical similarities to IST(16). This has led to consider ablation of the arcuate ridge as a treatment of refractory IST, necessitating larger trials to confirm its potential role.Phrenic nerve injury is a severe and dreaded complication of SN ablation(12). Pericarditis, right diaphragmatic paralysis, and SVC syndrome are other undesirable side effects of the procedures, variously reported in studies. but a common complication was observed in them all, atrial tachyarrhythmias(12). It has been hypothesized that myocardial pathology, such as inflammation and fibrosis, considered iatrogenic due to the ablation procedures, may be promoting arrhythmias both in the region of the SA node, as well as in remote locations(12). Through multivariable analysis, higher resting heart rates post-ablation and smaller cranial-to-caudal shifts have been defined as predictors of atrial arrhythmias(15). In conclusion, catheter ablation could be considered an effective treatment for highly symptomatic, drug-refractory patients, even for those who did not respond to SA node modification(5).The sinus node is located close to the epicardial surface and catheter-based ablations do not always make full-thickness lesions across the atrial muscle, leading to failure of the ablation(17), besides the numerous trabeculae and the widely variable anatomy.Surgical ablation is not a first-line or routine management strategy for IST, but it has been proposed when IST resists or recurs after SN modification/ endocardial ablation(17). Effectively, in several studies, epicardial lesions, through a single small incision in one of the intercostal spaces, successfully slowed heart rate and shifted activation to a more caudal location, and surprisingly, subsequent endocardial lesions led to an even greater drop in heart rate and more caudal site of earliest activation(18). These outcomes were again replicated when using minimally invasive thoracoscopic ablation of the epicardial site of the SA node, concluding of the promising efficacy and the safety of this approach, since it preserves the phrenic nerve(17), although continued follow-up after surgery is required.Medication-resistant IST remains a medical challenge for physicians and cardiologists; and in the era of great advances in interventional cardiology, its treatment remains debatable. Sinus node modification/ ablation is not recommended as first-line therapy in IST, this procedure should be considered only in drug-refractory patients who have severe symptoms(13). Although the number of patients in the available studies is generally small, both procedures have documented an encouraging success rate in the short-term, while being less impressive in the long-term. It has been hypothesized that this discrepancy is due to the relatively large potential area of atrial pacemaker cells(18); modification or ablation may fail to ablate or isolate all the pathways that comprise the functional SA node because they often target the anatomic part and the area of earliest atrial activation(19). Others have explained that the long-term slowing in rhythm fails because these procedures inconsistently produce transmural lesions in the right atrium. Surgical treatment of IST has proposed a solution to the latter conflict when isolating the SA node with a wide cuff of surrounding atrial muscle(19). And with the advent of bipolar RF clamps and minimally invasive cardiac surgical techniques with thoracoscopic guidance, this approach appears more appealing than before, especially when combined with endocardial ablation(19). But again, current data specifies employing these techniques in highly selected cases.

Jerome FERRARA

and 10 more

Background: There is insufficient evidence regarding the comparison of Rapid Deployment aortic valve replacement(RDAVR) to TAVR in intermediate-risk patients with severe symptomatic aortic stenosis(AS) Aims: We compare the 2-years outcomes between RDAVR with INTUITY and TAVR with SAPIEN 3 in intermediate-risk patients with AS. Methods: Inclusion criteria: severe AS implanted with RDAVR or TAVR; EUROSCORE II ≥ 4% and clinical evaluation by Heart Team. Regression adjustment for the propensity score was used to compare RDAVR with TAVR(1:1). Primary endpoint: composite criterion of death, disabling stroke or rehospitalization. Secondary endpoints: occurrence of major bleeding post-operative complications, paravalvular regurgitation (PVR)≥2 and patient-prosthesis mismatch(PPM) at 1 month and pacemaker implantation at 2 years. Results: A total of 152 patients were included from 2012 to 2018: 48 in the RDAVR group and 104 in the TAVR group. Mean age was 82.7±6, 51.3% were female, mean Euroscore II was 6.03±1.6% and mean baseline LVEF was 56±13%,mean indexed iEOA was 0.41±0.1cm/m2, mean gradient was 51.7±14.7mmHg. Patients with RDAVR were younger(79.5±6vs82.6±6,p=0.01), at higher risk (EUROSCORE2 6,61±1,8%vs5,63±1,5%, p=0.005), combined surgery was performed in 28 patients(58.3%). Twenty-two patients(45.99%) met the primary outcome in the RDAVR group and 32 patients(66.67%) in the TAVR group. By 1:1propensity score matching analysis, there was a significant difference between both groups in favor of RDAVR(HR=0.58[95%CI:0.34;1.00],p=0.04). No difference were observed in PPM occurrence(0.83;[0.35-1.94];p=0.67),major bleeding events(1.33;[0.47-3.93];p=0.59),PVR≥2(0.33[0-6.28],p=0.46), and pacemaker implantation (0.84[0.25-2.84],p=0.77).Conclusion: RDAVR is associated with better 2-years outcomes than TAVR in intermediate-risk patients with severe symptomatic AS.

Francesca Mori

and 10 more

Hakan Celikhisar

and 2 more

Abstract Objective: To evaluate whether smoking cessation has an effect on female sexual function and quality of life. Methodology: After approval by the local ethics committee, smoking and non-smoking female participants were included in the study and all participants filled the female sexual function index (FSFI) and the short form 36 (SF-36). The same questionnaires were filled again at the 9th month control after smoking cessation. The scores of these questionnaires were compared between the groups. In addition, the FSFI and SF-36 scores of the participants in the smoking group were also compared with the scores at the 9th month after smoking cessation. Results: The rate of FSD was significantly higher in the smoking group when compared with control group (86.0% vs 32.5%; p<0,001). The FSFI total and sub domains score was significantly lower in the smoking group when compared control group [21.5 (min:14.4-max:28.69) and 28.9 (min:17.7-max:32.8); p<0.001 respectively]. The rate of FSD was significantly decreased after nine months smoking cessation (86% to 35.1%; p<0.001). After smoking cessation significant improvements on FSFI total and sub-domain scores and SF-36 sub-domain scores were determined. Conclusion: In this study, it was shown that smoking negatively affected FSD and QOL when compared to healthy non-smoking women, and smoking cessation caused significant improvements in FSFI and SF-36 scores in these women after 9 months. Keywords: female sexual dysfunction, female sexual function index, smoking cessation, the Short Form 36, quality of life.

Carola Sauter-Louis

and 20 more

African swine fever (ASF) has spread across many countries in Europe since the introduction into Georgia in 2007. We report here on the first cases of ASF in wild boar detected in Germany close to the border with Poland. In addition to the constant risk of ASF virus (ASFV) spread through human activities, movements of infected wild boar also represent a route of introduction. Since ASF emerged in Western Poland in November 2019, surveillance efforts, in particular examination of wild boar found dead, were intensified in the regions of Germany bordering with Poland. The first case of ASF in wild boar in Germany was therefore detected by passive surveillance and confirmed on 10th September 2020. By 24th September 2020, 32 cases were recorded. Testing of samples from tissues of carcasses in different stages of decomposition yielded cycle threshold values from 18 to 36 in the OIE-recommended PCR which were comparable between the regional and national reference laboratory. Blood swabs yielded reliable results, indicating that the method is suitable also under outbreak conditions. Phylogenetic analysis of the ASFV whole-genome sequence generated from material of the first carcass detected in Germany, revealed that it groups with ASFV genotype II including all sequences from Eastern Europe, Asia and Belgium. However, some genetic markers including a 14 bp tandem repeat duplication in the O174L gene were confirmed that have so far been detected only in sequences from Poland (including Western Poland). Epidemiological investigations that include estimated postmortem intervals of wild boar carcasses of infected animals suggest that ASFV had been introduced into Germany in the first half of July 2020 or even earlier.

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