Termination Rate Research Articles

Real-world performance of a fully automatic antitachycardia pacing algorithm

Abstract Background Antitachycardia pacing (ATP) found in most implantable cardioverter defibrillators (ICDs) is an important therapy for painless termination of ventricular tachycardias (VT). In ICDs programmed to guideline-recommended detection and therapy settings typical ATP success rates are 50-70%.[1-3] The first closed-loop, automated ATP (AATP) algorithm, introduced in 2021, applies an S1 train derived from the detected VT, followed by an S2 derived initially from a refractory period estimator and then adjusted using analysis of the post-pacing interval if ATP fails. The termination efficacy of AATP in the real-world population is unknown. Purpose To assess the effectiveness AATP in a large real-world population. Methods A database of de-identified ICD transmissions from subjects in the United States, Australia, Canada, and New Zealand was queried for AATP treated episodes. ICDs were randomly sampled, biased toward ICDs with multiple treated VT episodes. For rhythms classified as monomorphic ventricular tachycardia, each AATP pulse train was reviewed for: rhythm at delivery, effect of ATP, and any non-capturing pulses. Acceleration was defined as a post-ATP decrease in MVT cycle length (VTCL) of at least 10% and at least 30ms. Acceleration to polymorphic VT or ventricular fibrillation (PVT/VF) was assessed. Rates of termination and acceleration were calculated for all MVT and dichotomized using a 320ms VTCL cutoff. The method of generalized estimating equations (GEE) was used to correct event rates for multiple episodes from a single patient. Results There were 2281 episodes of MVT in 340 patients; 63% of patients had 2 or more episodes. There were 724 episodes with initial VTCL <320ms and 1557 episodes with VTCL ≥320ms. The rate of termination of MVT by AATP was 78% for all VTCL [95% CI: 74%-81%]. In 300 patients (88%) AATP terminated at least one MVT. For MVT with VTCL ≥320ms the termination rate was 80% [95% CI: 75%-83%] and for VTCL <320ms the termination rate was 75% [95% CI: 69%-80%]. The rate of acceleration was 3.6% [95% CI: 2.7%-4.9%], with a 0.8% rate of acceleration to PVT/VF [95% CI: 0.4%-1.8%]. Acceleration led to shock therapy in 63% of accelerated episodes. All MVT accelerated to PVT/VF either spontaneously terminated (4/14) or were successfully converted by a single shock therapy (10/14). All accelerations that remained MVT were successfully treated by the device with either subsequent ATP (35%) or shock therapy (61%), or spontaneously terminated (4%). Conclusion In this large, real-world cohort analysis, automated ATP’s termination rate exceeded the typical success rate of burst ATP, particularly for MVT <320ms. Acceleration to PVT/VF was low and effective first-shock defibrillation was consistent. Subsequent ATP for accelerated MVT had incremental benefit, leading to successful termination one-third of the time. Additional data are currently being prospectively collected in a separate post-approval study.

Abstract 14702: Roles of Atrial Mass Reduction and Gaps on the Anti-Atrial Fibrillatory Effects of Pulmonary Vein Isolation: A Computational Modeling Study

Background: Although pulmonary vein isolation (PVI) is the basis of atrial fibrillation (AF) catheter ablation (AFCA), the conditional changes of an anti-AF effect and the wave-dynamic mechanism are poorly understood. Therefore, we compared the effects of PVI based on the ablation circumference, width, and number or locations of gaps with or without amiodarone at the same condition in realistic computational modeling of human AF. Hypothesis: An anatomical level of PVI and characteristics of the PVI gap would affect the anti-AF effects of the AFCA. Methods: We included 50 patients (76.0% persistent AF) who underwent AFCA. Realistic AF modeling reflecting the computed tomography (CT) and the electroanatomical map was performed on each patient. We compared the AF defragmentation rate (DeFR; change to atrial tachycardia (AT) or termination), termination rate (TnR), and changes in the dominant frequency (DF) and the number of phase singularities (PSs) based on the PVI level (antral vs. ostial), PVI width (single vs. 3х width), number and location of 2-mm PVI gaps with or without amiodarone (10mM). We randomly assigned the number and location of the PVI gaps to the AF models. Results: The antral PVI had a significantly higher DeFR (p for trend <0.001) and TnR (p for trend <0.001) than the ostial PVI, PVI gaps, or baseline AF. However, there was no difference depending on PVI width. Among the PVI gaps, the DeFR (p for trend<0.001) decreased as the gap number increased. Additional amiodarone increased DeFR (p=0.003) and TnR (p=0.034) and reduced DF (p<0.001) and the number of PSs (p<0.001) with PVI-gap, especially with a single PVI-gap. Conclusions: In this realistic computational modeling study with integrated patients’ atrial anatomy and electrophysiology, the atrial mass reduction depending on the anatomical PVI level, number of PVI gaps, and additional antiarrhythmic drug significantly affected the AF maintenance mechanisms.

Abstract 420: The Association Between Ventricular Fibrillation Duration and Successful Termination After the First Shock in Witnessed Out-of-Hospital Cardiac Arrest Patients

Introduction: In OHCA patients with an initial shockable rhythm, a longer time interval between onset of VF and the first shock decreases the likelihood of survival. The exact mechanism to explain this decrease is not clear. We investigated the time interval between delay to the first shock and outcomes VF termination, return of organized rhythm (ROOR), ROSC and survival. Methods: We studied witnessed OHCA patients with VF as an initial rhythm using the prospective ARREST registry. Patient- and resuscitation data, including time-synchronized AED and manual defibrillator data, were analysed to determine VF termination at 5 seconds after the first shock. Shock delay was defined as the time from initial emergency call till first shock by any defibrillator. Outcomes were rates of termination of VF, ROOR 5 seconds after the first shock, ROSC before transport, and survival to discharge, all in relation to the delay to the first shock. A logistic regression corrected for age, sex and basic life support before EMS arrival was used to analyse the association between VF duration and outcomes. Results: A total of 3676 cases were analysed. VF termination rates declined from 95% when the first shock was delivered <2 minutes after the call to 75% when delivered after >16 minutes (Figure 1). Rates of ROOR (49% to 23%), ROSC before transport (86% to 33%), and survival to discharge (79% to 23%) all declined significantly. Every additional minute in VF was associated with a 9% increased odds of failure to terminate VF (OR 1.09 [95% CI 1.07-1.12]), a 7% reduced odds of ROOR (OR 0.93 [95% CI 0.91-0.95]), a 12% reduced odds of acquiring ROSC before transport (OR 0.88 [95% CI 0.86-0.90]), and a 15% reduced odds of surviving to discharge (OR 0.85 [95% CI 0.83-0.87]). Conclusions: Every additional minute of delay to the first shock was associated with significant decreases in rates of VF termination, ROOR, and ROSC during transportation. This may explain the worse outcomes in patients with a long delay to defibrillation.

Abstract 16302: Beyond the Veins: A Critical Right Atrial Termination Site in High Burden Paroxysmal Atrial Fibrillation Identified Using Spatiotemporal Dispersion After Failure of High Quality Pulmonary Vein Isolation

Case Presentation: A 55 year-old female with two-year history of persistent atrial fibrillation (AF) presented for elective catheter ablation. Her smart watch recorded frequent prolonged episodes of AF, and event monitoring confirmed 71% AF burden. Metoprolol improved her symptoms only slightly. At the beginning of the procedure, patient’s rhythm was on sinus (NSR). During the completion of pulmonary vein isolation (PVI), the patient developed typical flutter, which degenerated into AF during ablation. Biatrial dispersion mapping in the right atrium (RA) revealed a single highly dispersed area in the posterior RA. Ablation at this site immediately terminated AF to NSR. The patient was non-inducible and remains free of AF. Discussion: Maintenance of NSR in AF is associated with improved clinical outcomes and quality of life. Catheter ablation has the highest efficacy for minimizing AF burden. PVI has a success rate of 67-89% in treating patients with paroxysmal AF and PVI alone is typically employed. A dispersion area is characterized by local clusters of electrograms which may or may not be fractionated, and display interelectrode time and space dispersion such that activation is spread over the entire AF cycle length. Identification and ablation of dispersion regions in persistent AF has demonstrated a high acute termination rate and improved outcomes in early follow-up, but is difficult to reproduce (Seitz et al. 2017). Here, we present a case of a patient with high burden paroxysmal AF who underwent PVI but remained in AF. Using visual dispersion mapping, we were able to identify a critical RA dispersion area, which rendered patient non-inducible (Figure 1).

Pathological Findings in Fetuses Terminated for Suspected Lower Urinary Tract Obstruction: Experience From a High-Risk Fetal Center in Canada.

Pregnancies complicated by prenatally suspected lower urinary tract obstruction (LUTO) can be associated with high rates of terminations due to potentially poor outcomes. Herein, we assessed autopsy findings of fetuses terminated for suspected LUTO to evaluate the prenatal diagnostic accuracy and spectrum of underlying pathologies. We performed a retrospective review of all pregnancies referred to a high-risk fetal center in a universal access to care health care system for suspected LUTO that opted for termination of pregnancy between 2009 and 2022. Ultrasound features, genetic investigations, placental findings, and distribution of postmortem diagnoses were assessed. Of a total of 190 pregnancies with suspected LUTO evaluated during the study period, 79 (42%) were terminated. We excluded 35 fetuses with incomplete data, resulting in 44 available for analysis. Pregnancies were terminated at a mean gestation of 22 ± 5 weeks. A LUTO diagnosis was confirmed in 37 (84.1%) fetuses (35 males, 2 females), and the remaining 7 showed other pathologies. Pulmonary hypoplasia was found in 62.2% (n = 23) and placental pathologies in 56.8% of confirmed LUTO compared to 33.4% and 71.4% in non-LUTO cases, respectively. Overall, a total of 31 fetuses underwent additional prenatal investigations with genetic anomalies detected only in fetuses with a confirmed LUTO diagnosis (13.6%). In our health care system, almost half of prenatally suspected LUTO pregnancies are terminated. The sonographic diagnostic accuracy for LUTO is reasonable at 84%. However, the remaining 16% still had significant pathologies. Genetic abnormalities are uncommon and rarely the trigger for pregnancy terminations.

Kinetic Study of <i>para</i>-<i>tert</i>-Butylcumene Oxidation in the Presence of <i>N</i>-Hydroxyphthalimide

The kinetics of the oxidation of para-tert-butylcumene to hydroperoxide by molecular oxygen in the presence of N-hydroxyphthalimide has been studied. Based on the study of the regularities in the formation of hydroperoxide and non-target reaction products, a mathematical model of the process was obtained that adequately describes the change in the main components of the reaction concentration over time. The main role of N-hydroxyphthalimide is that it converts peroxide radicals into the corresponding hydroperoxides, thereby reducing the formation of non-target reaction products by reducing the quadratic termination rate. Simultaneously formed N-oxyphthalimide radicals increase the rate of hydrocarbon oxidation. Thus, the use of N-hydroxyphthalimide in hydrocarbon oxidation processes results in an increase in the rate and selectivity of hydroperoxide formation.

The new face of cystic fibrosis in the era of population genetic carrier screening

BackgroundPopulation genetic carrier screening (PGCS) for cystic fibrosis (CF) has been offered to couples in Israel since 1999 and was included in a fully subsidized national program in 2008. We evaluated the impact of PGCS on CF incidence, genetic and clinical features. MethodsThis was a retrospective national study. Demographic and clinical characteristics of children with CF born in Israel between 2008 and 2018 were obtained from the national CF registry and from patients' medical records. Data on CF births, preimplantation genetic testing (PGT), pregnancy termination and de-identified data from the PGCS program were collected. ResultsCF births per 100,000 live births decreased from 8.29 in 2008 to 0.54 in 2018 (IRR = 0.84, p < 0.001). The CF pregnancy termination rate did not change (IRR = 1, p= 0.9) while the CF-related PGT rate increased markedly (IRR = 1.33, p < 0.001). One hundred and two children were born with CF between 2008 and 2018 with a median age at diagnosis of 4.8 months, range 0–111 months. Unlike the generally high uptake nationally, 65/102 had not performed PGCS. Even if all had utilized PGCS, only 51 would have been detected by the existing genetic screening panel. Clinically, 34 % of children were pancreatic sufficient compared to 23 % before 2008 (p = 0.04). ConclusionsSince institution of a nationwide PGCS program, the birth of children with CF decreased markedly. Residual function variants and pancreatic sufficiency were more common. A broader genetic screening panel and increased PGCS utilization may further decrease the birth of children with CF.

Recurring Rolling/Crimping Effects on Termination Effectiveness of Iron Clay Pea and Pearl Millet Warm-Season Cover Crops

Summer cover crop utilization by no-till vegetable farms is essential for continuous soil protection, especially in the southern United States where intense storms are likely to occur in hot and humid summer months. A field experiment was conducted at the National Soil Dynamics Laboratory in Auburn, AL, USA, between the summers of 2015 and 2017 to determine the effectiveness of an experimental roller/crimper in mechanically terminating summer cover crops. Iron clay peas (Vigna unguiculata, L.) planted on a sandy loam and pearl millet (Penninsetum glaucum, L.) planted on clay soil were selected to determine termination rate effectiveness in single, double, and triple rolling/crimping over the same area. Overall, termination rates for both cover crops were higher for rolling three times (71%) compared to rolling once (55%) or twice (63%). However, cover crop termination was inhibited due to rainfalls on the experimental area during the three-week evaluation period. In 2016, drought conditions and high temperatures (32.6 °C) caused biomass reduction, especially for pearl millet, of over 31% to 39% compared to 2017 and 2015. Rolling provided higher soil-water conservation compared with the non-rolled control due the cover crop mulch layer blocking sunlight, keeping the soil surface cooler and preventing water evaporation. Recurrent rolling did not cause soil compaction above the 2.0 MPa level that inhibits root growth, but changes in soil strength were dependent on the soil moisture content.

Small-for-gestational-age fetus diagnosed in the second trimester: Possible etiologies and short-term neonataloutcomes.

The aim of our study was to investigate the causes of fetal growth <10th centile diagnosed <26 weeks' gestation in singleton pregnancies and compare pregnancy outcomes in relation to the identified etiology. Historical cohort study conducted in two Italian hospitals which included all small-for-gestational-age fetuses diagnosed between 18+0 and 26+0 weeks over a 10-year period. Fetuses were divided into three groups depending on the prenatally suspected etiology: chromosomal abnormalities (Group 1), malformations (Group 2) and isolated (Group 3). These groups were compared regarding pregnancy outcomes. Fetuses in Group 3 were divided into small-for-gestational-age and fetal growth restriction following the Delphi Consensus criteria and the outcomes were further compared. Fisher's Exact or Mann-Whitney test were used for comparison of groups. In all, 435 fetuses were included. Of these, 20 cases (4.6%) were associated with chromosomal abnormalities (Group 1), 98 (22.5%) with fetal malformations (Group 2) and 317 (72.9%) were isolated (Group 3). A higher percentage of live births was reported for Group 3 (P < 0.001). Termination of pregnancy was more common in Group 1 (P < 0.001). No differences in gestational age at delivery, birthweight, intrauterine death or neonatal death were detected within groups. Growth-restricted fetuses had lower gestational age at delivery, birthweight and number of live births (P < 0.001), higher rates of termination of pregnancy, intrauterine death (P < 0.001) and neonatal death <10 days (P = 0.002) compared to small-for-gestational-age. In 17 cases a chromosomal abnormality, genetic syndrome or adverse neurological outcome was diagnosed after birth: six from Group 2 (11.3% of live births in this group) and 11 from Group 3 (4.3%). We report that fetal growth <10th percentile diagnosed before 26 weeks is not isolated before birth in 27% of cases. Malformations and chromosomal abnormalities are common etiologies; therefore, detailed anomaly scans and invasive testing should be offered. In addition, there is a residual risk of neonatal death and postnatal diagnosis of a genetic syndrome or neurodevelopmental impairment despite normal prenatal tests. These results expand the small amount of information on the outcome of cases with very early diagnosis of impaired fetal growth currently available and highlight the importance of detailed counseling with couples.

Pregnancy Termination and Postnatal Major Congenital Heart Defect Prevalence After Introduction of Prenatal Cardiac Screening

Prenatal cardiac screening of the first and second trimesters has had a major impact on postnatal prevalence of congenital heart defects (CHDs), rates of termination of pregnancy (TOP), and outcomes among children born alive with CHDs. To examine the prenatal and postnatal incidence of major CHDs (ie, necessitating intervention within the first year of life), detection rate trends, rates of TOP, and the association of cardiac screening with postnatal outcomes. In this cross-sectional study, 3827 fetuses with antenatally diagnosed major CHDs in the Czech Republic (population 10.7 million) between 1991 and 2021 were prospectively evaluated with known outcomes and associated comorbidities. Prenatal and postnatal prevalence of CHD in an unselected population was assessed by comparison with a retrospective analysis of all children born alive with major CHDs in the same period (5454 children), using national data registry. Data analysis was conducted from January 1991 to December 2021. Prenatal detection and postnatal prevalence of major CHDs and rate of TOPs in a setting with a centralized health care system over 31 years. A total of 3 300 068 children were born alive during the study period. Major CHD was diagnosed in 3827 fetuses, of whom 1646 (43.0%) were born, 2069 (54.1%) resulted in TOP, and 112 (2.9%) died prenatally. The prenatal detection rate increased from 6.2% in 1991 to 82.8% in 2021 (P < .001). Termination of pregnancy decreased from 70% in 1991 to 43% (P < .001) in 2021. Of 627 fetuses diagnosed in the first trimester (introduced in 2007), 460 were terminated (73.3%). Since 2007, of 2066 fetuses diagnosed in the second trimester, 880 (42.6%) were terminated, resulting in an odds ratio of 3.6 (95% CI, 2.8-4.6; P < .001) for TOP in the first trimester compared with the second trimester. Postnatal prevalence of major CHDs declined from 0.21% to 0.14% (P < .001). The total incidence (combining prenatal detection of terminated fetuses with postnatal prevalence) of major CHD remained at 0.23% during the study period. In this cross-sectional study, the total incidence of major CHD did not change significantly during the 31-year study period. The prenatal detection of major CHD approached 83% in the current era. Postnatal prevalence of major CHD decreased significantly due to early TOPs and intrauterine deaths. The introduction of first trimester screening resulted in a higher termination rate in the first trimester but did not revert the overall decreasing trend of termination for CHDs in general.

Exome sequencing improves genetic diagnosis of congenital orofacial clefts.

Objective: This retrospective study aims to evaluate the utility of exome sequencing (ES) in identifying genetic causes of congenital orofacial clefts (OFCs) in fetuses with or without other structural abnormalities, and to further explore congenital OFCs genetic causes. Methods: The study enrolled 107 singleton pregnancies diagnosed with fetal OFCs between January 2016 and May 2022, and categorized them into two groups: isolated cleft lip and/or palate (CL/CP) and syndromic CL/CP. Cases with positive karyotyping and chromosomal microarray analysis results were excluded. Whole-exome sequencing was performed on eligible fetuses and their parents. Monogenic variants identified by ES and perinatal outcomes were recorded and evaluated during postnatal follow-up. Results: Clinically significant variants were identified in 11.2% (12/107) of fetuses, with no significant difference in detection rate between the isolated CL/CP group and the syndromic CL/CP group (8/83, 9.6% vs. 4/24, 16.7%, p = 0.553). Additionally, sixteen (16/107, 15.0%) fetuses had variants of uncertain significance. We identified 12 clinically significant variations that correlated with clinical phenotypes in 11 genes from 12 fetuses, with CHD7 being the most frequently implicated gene (n = 2). Furthermore, we observed a significant difference in termination rates and survival rates between the isolated CL/CP and syndromic CL/CP groups (41.0% vs. 70.8% and 56.6% vs. 20.8%, p < 0.05 for both). Conclusion: Based on our findings, it is clear that ES provides a significant increase in diagnostic yield for the molecular diagnosis of congenital OFCs, thereby substantially improving the existing prenatal diagnostic capabilities. This study also sheds light on seven novel pathogenic variants, broadening our understanding of the genetic underpinnings of OFCs and expanding the disease spectrums of relevant genes.

Cardiac Arrest Survival at Emergency Medical Service Agencies in Catchment Areas With Primarily Black and Hispanic Populations

Black and Hispanic patients are less likely to survive an out-of-hospital cardiac arrest (OHCA) than White patients. Given the central importance of emergency medical service (EMS) agencies in prehospital care, a better understanding of OHCA survival at EMS agencies that work in Black and Hispanic communities and White communities is needed to address OHCA disparities. To examine whether EMS agencies serving catchment areas with primarily Black and Hispanic populations (Black and Hispanic catchment areas) have different rates of OHCA survival than agencies serving catchment areas with primarily White populations (White catchment areas). A cohort study including adults with nontraumatic OHCA from January 1, 2015, to December 31, 2019, in the Cardiac Arrest Registry to Enhance Survival was conducted. Data analysis was conducted from August 17, 2022, to July 7, 2023. Emergency medical service agencies, categorized as working in catchment areas where the combination of Black and Hispanic residents made up more than 50% of the population or where White residents made up more than 50% of the population. The unit of analysis was the EMS agency. The primary outcome was agency-level risk-standardized survival rates (RSSRs) to hospital admission for OHCA at each EMS agency, which were calculated using hierarchical logistic regression and compared between agencies serving Black and Hispanic and White catchment areas. Whether differences in OHCA survival were explained by EMS and first responder measures was evaluated with additional adjustment for these factors. Among 764 EMS agencies representing 258 342 OHCAs, 82 EMS agencies (10.7%) had a Black and Hispanic catchment area. Overall median age of the patients was 63.0 (IQR, 52.0-75.0) years, 36.1% were women, and 63.9% were men. Overall, the mean (SD) RSSR was 27.5% (3.6%), with lower survival at EMS agencies with Black and Hispanic catchment areas (25.8% [3.6%]) compared with agencies with White catchment areas (27.7% [3.5%]; P < .001). Among the 82 EMS agencies with Black and Hispanic catchment areas, a disproportionately higher number (32 [39.0%]) was in the lowest survival quartile, whereas a lower number (12 [14.6%]) was in the highest survival quartile. Additional adjustment for EMS response times, EMS termination of resuscitation rates, and first responder rates of initiating cardiopulmonary resuscitation or applying an automated external defibrillator before EMS arrival did not meaningfully attenuate differences in RSSRs between agencies with Black and Hispanic compared with White catchment areas (mean [SD] RSSRs after adjustment, 25.9% [3.3%] vs 27.7% [3.1%]; P < .001). Risk-standardized survival rates for OHCA were 1.9% lower at EMS agencies working in Black and Hispanic catchment areas than in White catchment areas. This difference was not explained by EMS response times, rates of EMS termination of resuscitation, or first responder rates of initiating cardiopulmonary resuscitation or applying an automated external defibrillator. These findings suggest there is a need for further assessment of these discrepancies.

Clinical and genetic aspects of termination of pregnancy; tertiary center experience.

The aim of the study was to retrospectively analyze the indications Techniques and complications of pregnancy termination performed in a tertiary center. All cases between 10 and 33 weeks of gestation between January 2021 and June 2023 were retrospectively analyzed. The patients were divided into two groups as group 1 with 11+0 to 21+6 gestational weeks and group 2 for those at 22+0 and 33+0 gestational weeks. A total of 568 pregnancy terminations were included in the study. Among all terminations the most common fetal indications were central nervous system anomalies (148 cases, 26%) and trisomy 21 (53 cases, 9%) and the most common maternal/obstetrical Indication was previable premature rupture of the membranes (179 cases, 31.5%). Abnormal genetic results were found in 50 of 173 cases (28.9%) with a termination indication of Structural malformation who accepted invaziv genetic testing. The number of terminations with fetal indications performed after 22 weeks were 148 (41%) and 11 (7.4%) cases of these late terminations of pregnancy were anomalies expected to be diagnosed in the first trimester. Complication rates (12.4%) and abdominal termination rates (3.5%) were significantly higher in group 2 than in group 1 (p<0.05). Improvements in prenatal genetic screening and diagnostic techniques will undoubtedly decrease the gestational ages in terminations of pregnancies. However, there will always be cases that can neither be diagnosed earlier nor can be treated due to the nature of the anomaly. In the management of such cases, terminations will always occupy an important place in prenatal care.

Trends in Management of Fetuses with Suspected Lower Urinary Tract Obstruction (LUTO): A High-Risk Fetal and Pediatric Center Experience in a Universal-Access-to-Care System.

Neonates with lower urinary tract obstruction (LUTO) experience high morbidity and mortality associated with the development of chronic kidney disease. The prenatal detection rate for LUTO is less than 50%, with late or missed diagnosis leading to delayed management and long-term sequelae in the remainder. We aimed to explore the trends in prenatal detection and management at a high-risk fetal center and determine if similar trends of postnatal presentations were noted for the same period. Prenatal and postnatal LUTO databases from a tertiary fetal center and its associated pediatric center between 2009 and 2021 were reviewed, capturing maternal age, gestational age (GA) at diagnosis, and rates of termination of pregnancy (TOP). Time series analysis using autocorrelation was performed to investigate time trend changes for prenatally suspected and postnatally confirmed LUTO cases. A total of 161 fetuses with prenatally suspected LUTO were identified, including 78 terminations. No significant time trend was found when evaluating the correlation between time periods, prenatal suspicion, and postnatal confirmation of LUTO cases (Durbin-Watson [DW] = 1.99, p = 0.3641 and DW = 2.86, p = 0.9113, respectively). GA at referral was 20.0 weeks (interquartile range [IQR] 12, 35) and 22.0 weeks (IQR 13, 37) for TOP and continued pregnancies (p < 0.0001). GA at initial ultrasound was earlier in terminated fetuses compared to continued (20.0 [IQR 12, 35] weeks vs. 22.5 [IQR 13, 39] weeks, p < 0.0001). While prenatal LUTO suspicion remained consistently higher than postnatal presentations, the rates of postnatal presentations and terminations remained stable during the study years (p = 0.7913 and 0.2338), as were GA at TOP and maternal age at diagnosis (p = 0.1710 and 0.1921). This study demonstrated that more severe cases of LUTO are referred earlier and are more likely to undergo TOP. No significant trend was detected between time and prenatally suspected or postnatally confirmed LUTO, highlighting the need for further studies to better delineate factors that can increase prenatal detection.

Fetal hyperechoic kidney cohort study and a meta-analysis.

Objective: To investigate the positive rate of chromosomal and monogenic etiologies and pregnancy outcomes in fetuses with hyperechoic kidney, and to provide more information for genetic counseling and prognosis evaluation. Methods: We performed a retrospective analysis of 25 cases of hyperechoic kidney diagnosed prenatal in the Second Affiliated Hospital of Harbin Medical University and Harbin Red Cross Central Hospital (January 2017-December 2022). Furthermore, we conducted a meta-analysis of a series of hyperechoic kidneys (HEK) in the literature to assess the incidence of chromosomal and monogenic etiologies, mortality, and pooled odds ratio (OR) estimates of the association between the incidence of these outcomes and other associated ultrasound abnormalities. Results: 25 fetuses of HEK were enrolled in the cohort study, including 14 with isolated hyperechoic kidney (IHK) and 11 with non-isolated hyperechoic kidney (NIHK). Chromosomal aneuploidies were detected in 4 of 20 patients (20%). The detection rate of pathogenic or suspected pathogenic copy number variations (CNVs) was 29% (4/14) for IHK and 37% (4/11) for NIHK. Whole exome sequencing (WES) was performed in 5 fetuses, and pathogenic genes were detected in all of them. The rate of termination of pregnancy was 56% in HEK. 21 studies including 1,178 fetuses were included in the meta-analysis. No case of abnormal chromosome karyotype or (intrauterine death)IUD was reported in fetuses with IHK. In contrast, the positive rate of karyotype in NIHK was 22% and that in HEK was 20%, with the ORs of 0.28 (95% CI 0.16-0.51) and 0.25, (95% CI 0.14-0.44), respectively. The positive rate of (chromosome microarray analysis) CMA in IHK was 59% and that in NIHK was 32%, with the ORs of 1.46 (95% CI 1.33-1.62) and 0.48 (95% CI, 0.28-0.85), respectively. The positive rate of monogenic etiologies in IHK was 31%, with the OR of 0.80 (95% CI 0.25-2.63). In IHK, the termination rate was 21% and neonatal mortality was 13%, with the ORs of 0.26 (95% CI, 0.17-0.40), 1.72 (95% CI, 1.59-1.86), and that in NIHK was 63%, 0.15 (95% CI, 0.10-0.24); 11%, 0.12 (95% CI, 0.06-0.26), respectively. The intrauterine mortality in NIHK group was 2%, with the OR of 0.02 (95% CI, 0.01-0.05). HNF1B variant has the highest incidence (26%) in IHK. Conclusion: The positive rate of karyotype was 20% in HEK and 22% in NIHK. The positive rate of CMA was 32% in NIHK and 59% in IHK. The positive rate of IHK monogenic etiologies was 31%. HNF1B gene variation is the most common cause of IHK. The overall fetal mortality rate of NIHK is significantly higher than that of IHK. The amount of amniotic fluid, kidney size and the degree of corticomedullary differentiation have a great impact on the prognosis, these indicators should be taken into consideration to guide clinical consultation and decision-making.

Association of prenatal thoracic ultrasound abnormalities with copy number variants at a single Chinese tertiary center.

To systematically evaluate the association of prenatal thoracic ultrasound abnormalities with copy number variants (CNVs). Chromosomal microarray (CMA) data and clinical characteristics from fetuses with thoracic ultrasound abnormalities were retrieved and analyzed. Thoracic ultrasound findings were mainly isolated except for fetal pleural effusion (FPE) and pulmonary hypoplasia. The diagnostic yield of CMA for thoracic anomaly was 9.66%, and FPE (17/68, 25%), pulmonary hypoplasia (1/8, 12.5%), and congenital diaphragmatic hernia (CDH) (6/79, 7.59%) indicated relatively high pathogenic/likely pathogenic (P/LP) CNV findings. The detection rate for P/LP CNVs was obviously increased in non-isolated thoracic anomalies (27.91% vs. 1.96%, P < 0.0001), non-isolated FPE (37.78% vs. 0%, P = 0.0007) and non-isolated congenital pulmonary airway malformation (CPAM) (27.27% vs. 0%, P < 0.0001), and significantly different among thoracic anomalies. Additionally, the rate of termination of pregnancy in cases with non-isolated thoracic anomalies (58.49% vs. 12.34%, P < 0.0001) and P/LP CNVs (85.71% vs. 24.15%, P < 0.0001) was obviously increased. The present study expanded phenotype spectrums for particular recurrent CNVs. FPE, CDH, and pulmonary hypoplasia indicated relatively high P/LP CNV findings among common thoracic ultrasound abnormalities, CPAM associated with other ultrasound abnormalities increased the incidence of diagnostic CNVs, while bronchopulmonary sequestration might not be associated with positive CNVs. The present data recommended CMA application for cases with prenatal thoracic ultrasound abnormalities, especially non-isolated FPE, non-isolated CPAM, CDH, and pulmonary hypoplasia.

Early and established status epilepticus: The impact of timing of intervention, treatment escalation and dosing on outcome

ObjectiveWe investigated the management and outcome of early and established status epilepticus including timing, dosing and selection of benzodiazepines along with the timing and efficacy of second line treatments. MethodsRetrospective single tertiary centre observational cohort study to identify all cases of SE between January 2019 and February 2022. Results252 cases were identified. Seizures terminated spontaneously in 136 (54%) cases. 116 (46%) were given benzodiazepines, of which 29 (25%) were given at least one benzodiazepine by family/carers, and 72 (62.1%) received benzodiazepines by ambulance services. Benzodiazepines terminated seizures in 83 (71.6%) cases. The commonest benzodiazepine used was buccal midazolam (35.5%). Median time to first benzodiazepine was 14.5 (6–27) minutes. There was a positive correlation between time to first benzodiazepine and time to seizure cessation, progression to second- and third-line treatment, and respiratory complications (p<0.05). 73 (62.9%) cases received a correct benzodiazepine dose. Benzodiazepine underdosing was associated with longer seizure duration (p<0.05). 33 (28.4%) cases progressed to second-line treatment where mean time to treatment was 59.4 min (±32.3 min). The commonest second-line treatment was Levetiracetam (53.8%), followed by Phenytoin (43.6%) with SE termination in 57.5% cases. 14 (12.1%) cases progressed to third-line treatment; mean time to treatment was 60.6 min (±22.24 min). Respiratory complications occurred in 17 (6.75%) cases; none due to benzodiazepines. There were two deaths in refractory SE. ConclusionEarly administration of benzodiazepines and optimal dosing is associated with a higher rate of SE termination. Levetiracetam was the most commonly used second line treatment.

Safety and Effectiveness of Chemotherapy in Elderly Biliary Tract Cancer Patients.

The safety and effectiveness of chemotherapy in elderly patients with biliary tract cancer (BTC) remain unclear. Therefore, we retrospectively reviewed patients who underwent chemotherapy for locally advanced, metastatic, or recurrent BTC at our institution from January 2016 to December 2021. Of the 283 included patients, 91 (32.5%) were aged 75 years or older when initiating chemotherapy. Elderly patients were more likely than non-elderly patients to receive monotherapy with gemcitabine or S-1 (58.7% vs. 9.4%, p < 0.001) and were less likely to experience grade 3-4 toxicities (55.4% vs. 70.2%, p = 0.015). The rates of termination due to intolerance (6.5% vs. 5.8%, p = 0.800) and transition to second-line chemotherapy (39.1% vs. 40.3%, p = 0.849) were similar between groups. In the overall cohort, age was not an independent predictor of overall survival (OS). Within the elderly cohort, there were no differences in severe adverse events between patients receiving monotherapy and combination therapy (50.0% vs. 63.2%, p = 0.211). Median OS was longer in the combination therapy group (10.4 vs. 14.1 months; p = 0.010); however, choice of monotherapy was not an independent predictor of overall survival. Monotherapy appears to be a viable alternative in selected elderly BTC patients.

Global Termination and Recurrence Macro Trends: A Follow-Up to Licklider and Dixon

ABSTRACT In this Special 25th Anniversary Issue, we (re)examine several macro historical trends concerning civil war termination and recurrence that were raised in the journal’s first issue by Roy Licklider and then followed-up on 10 years later by Jeffrey Dixon. These trends have to do with: (1) the global prevalence of recurrence; (2) the global prevalence of termination types; (3) patterns of recurrence by termination type, and (4) post-conflict patterns of civilian victimisation by termination type. With the advantage of more comprehensive and more systematised data, the analysis identifies several structural breaks in termination and recurrence trends, as well as differences in how outcomes regulate the inflow and outflow of fighting groups in countries. Over decades, conflict recurrence has been becoming more and more concentrated in a smaller subset of countries, and the majority of conflict recurrences are caused by new groups and not by previously terminated groups. Around 59 per cent of recurrences following peace accords are caused by new groups with no prior appearance in the conflict record, while 71 per cent of recurrences following government victory are caused by new groups. Since 2010, termination rates have declined by 25 per cent and recurrence rates have risen 44 per cent compared to the period 1990–2009. In addition, new conflicts entering the system after 2010 are up 150 per cent. As a result of these macro trends, the number of ongoing civil wars in the world is currently at an all time high.

Oxidation of Methyl Linoleate in Triton X‐100 Micelles Initiated by Lipid‐soluble Initiator 2,2′‐Azobis (2,4‐dimethylvaleronitrile)

AbstractThis article discusses the oxidation of methyl linoleate in micelles, initiated by the lipid‐soluble initiator 2,2′‐azobis (2,4‐dimethylvaleronitrile) (AMVN). It was shown that the rate constant (ki) is initiated in micelles for AMVN significantly lower than the known rate constant of initiation in true solutions. This can be explained by the reduced probability of AMVN radicals leaving the cage and an increase in the rate of chain termination between initiator radicals under conditions of low oxygen content. This conclusion was confirmed by quantum chemical calculations. Surprisingly, when determining the AMVN initiation rate constant for the consumption of nitroxyl radicals (&gt;NO⋅), the ki depends on the concentration &gt;NO⋅, this is due to the dependence of the probability of the nitroxyl radical and initiator radicals in micelles meeting on their concentration. Upon initiation of AMVN, no hydroperoxyl radical is expelled.