Biallelic PKP2 loss of function variants are associated with a lethal perinatal-onset biventricular dilated cardiomyopathy with excessive trabeculations and ventricular septal defects.

Homozygous plakophilin-2 (PKP2) variants have been identified as a cause of a lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET) in three cases. We report three more cases from two families with homozygous pathogenic PKP2 variants and perinatal-onset, lethal DCM-ET. Identification of the genetic abnormalities played a key role in decision-making and family counselling in these cases. This case series supports the published evidence that biallelic loss of function PKP2 variants cause a lethal, perinatal-onset cardiomyopathy.

Congenitally Corrected Transposition of the Great Arteries in Utero: Morphological Spectrum, Outcomes and Pitfalls in Fetal Diagnosis.

Congenitally corrected transposition of the great arteries (ccTGA) is a rare malformation with diverse morphology. We assessed features of fetuses with ccTGA and evaluated neonatal and pediatric outcomes. This was a retrospective review of fetuses with ccTGA at Birmingham Women's and Children's Hospital born from 2005 to 2019. Of thirty-six fetuses identified, six had unavailable prenatal data, one was postnatally diagnosed with isomerism and 29 fetuses were evaluated. ccTGA without associated cardiac lesions was found in 28% (8/29), ccTGA with significant VSD in 31% (9/29), ccTGA with pulmonary obstruction in 24% (7/29) and ccTGA with complex anomalies in 17% (5/29). Tricuspid regurgitation (TR) was observed in 17% (5/29) and heart block (HB) in 10% (3/29) prenatally. Six, that is 21% underwent genetic testing of which one was abnormal. Five extra-cardiac anomalies were reported prenatally and postnatally. Pregnancy was discontinued in five, of which two had moderate TR. There were thirty-one liveborn. Coarctation of the aorta was found in five postnatally but not suspected prenatally. In one, pulmonary stenosis was underestimated; otherwise, prenatal morphology was confirmed. Cardiac interventions were performed in 77% (24/31) liveborn with 39% (12/31) undergoing neonatal intervention. Overall, 6/31 liveborn died including all three with prenatal heart block and one with TR. Estimated survival for all liveborn at 1, 5 and 10 years was 87% (95% CI 76-100%), 83% (95% CI 72-98%) and 80% (95% CI 66-96%) respectively. Accurate prenatal diagnosis of ccTGA is critical for counseling. Early outcomes are favorable with 77% of liveborn undergoing surgery. Fetuses with prenatal diagnosis of complex associated abnormalities, HB and TR appear to do less well.

Impact of Intermittent Presumptive Treatment for Malaria in Pregnancy on Hospital Birth Outcomes on the Kenyan Coast.

BACKGROUND: Intermittent preventive treatment (IPTp) for pregnant women with sulfadoxine-pyrimethamine (SP) is widely implemented for the prevention of malaria in pregnancy and adverse birth outcomes. The efficacy of SP is declining, and there are concerns that IPTp may have reduced impact in areas of high resistance. We sought to determine the protection afforded by SP as part of IPTp against adverse birth outcomes in an area with high levels of SP resistance on the Kenyan coast. METHODS: A secondary analysis of surveillance data on deliveries at the Kilifi County Hospital between 2015 and 2021 was undertaken in an area of low malaria transmission and high parasite mutations associated with SP resistance. A multivariable logistic regression model was developed to estimate the effect of SP doses on the risk of low birthweight (LBW) deliveries and stillbirths. RESULTS: Among 27 786 deliveries, 3 or more doses of IPTp-SP were associated with a 27% reduction in the risk of LBW (adjusted odds ratio [aOR], 0.73; 95% confidence interval [CI], .64-.83; P < .001) compared with no dose. A dose-response association was observed with increasing doses of SP from the second trimester linked to increasing protection against LBW deliveries. Three or more doses of IPTp-SP were also associated with a 21% reduction in stillbirth deliveries (aOR, 0.79; 95% CI, .65-.97; P = .044) compared with women who did not take any dose of IPTp-SP. CONCLUSIONS: The continued significant association of SP on LBW deliveries suggests that the intervention may have a non-malaria impact on pregnancy outcomes.

Cycle Threshold Values as Indication of Increasing SARS-CoV-2 New Variants, England, 2020-2022.

Early detection of increased infections or new variants of SARS-CoV-2 is critical for public health response. To determine whether cycle threshold (Ct) data from PCR tests for SARS-CoV-2 could serve as an early indicator of epidemic growth, we analyzed daily mean Ct values in England, UK, by gene target and used iterative sequential regression to detect break points in mean Ct values (and positive test counts). To monitor the epidemic in England, we continued those analyses in real time. During September 2020-January 2022, a total of 7,611,153 positive SARS-CoV-2 PCR test results with Ct data were reported. Spike (S) gene target (S+/S-)-specific mean Ct values decreased 6-29 days before positive test counts increased, and S-gene Ct values provided early indication of increasing new variants (Delta and Omicron). Our approach was beneficial in the context of the first waves of the COVID-19 pandemic and can be used to support future infectious disease monitoring.

Model-based evaluation of admission screening strategies for the detection and control of carbapenemase-producing Enterobacterales in the English hospital setting.

BACKGROUND: Globally, detections of carbapenemase-producing Enterobacterales (CPE) colonisations and infections are increasing. The spread of these highly resistant bacteria poses a serious threat to public health. However, understanding of CPE transmission and evidence on effectiveness of control measures is severely lacking. This paper provides evidence to inform effective admission screening protocols, which could be important in controlling nosocomial CPE transmission. METHODS: CPE transmission within an English hospital setting was simulated with a data-driven individual-based mathematical model. This model was used to evaluate the ability of the 2016 England CPE screening recommendations, and of potential alternative protocols, to identify patients with CPE-colonisation on admission (including those colonised during previous stays or from elsewhere). The model included nosocomial transmission from colonised and infected patients, as well as environmental contamination. Model parameters were estimated using primary data where possible, including estimation of transmission using detailed epidemiological data within a Bayesian framework. Separate models were parameterised to represent hospitals in English areas with low and high CPE risk (based on prevalence). RESULTS: The proportion of truly colonised admissions which met the 2016 screening criteria was 43% in low-prevalence and 54% in high-prevalence areas respectively. Selection of CPE carriers for screening was improved in low-prevalence areas by adding readmission as a screening criterion, which doubled how many colonised admissions were selected. A minority of CPE carriers were confirmed as CPE positive during their hospital stay (10 and 14% in low- and high-prevalence areas); switching to a faster screening test pathway with a single-swab test (rather than three swab regimen) increased the overall positive predictive value with negligible reduction in negative predictive value. CONCLUSIONS: Using a novel within-hospital CPE transmission model, this study assesses CPE admission screening protocols, across the range of CPE prevalence observed in England. It identifies protocol changes-adding readmissions to screening criteria and a single-swab test pathway-which could detect similar numbers of CPE carriers (or twice as many in low CPE prevalence areas), but faster, and hence with lower demand on pre-emptive infection-control resources. Study findings can inform interventions to control this emerging threat, although further work is required to understand within-hospital transmission sources.

Medium-term Outcome of Prenatally Diagnosed Hypoplastic Left-Heart Syndrome and Impact of a Restrictive Atrial Septum Diagnosed in-utero.

OBJECTIVE: Surgical outcome data differs from overall outcomes of prenatally diagnosed fetuses with hypoplastic left heart syndrome (HLHS). Our aim was to describe outcome of prenatally diagnosed fetuses with this anomaly. METHODS: Retrospective review of prenatally diagnosed classical HLHS at a tertiary hospital over a 13-year period, estimated due dates 01/08/2006 to 31/12/2019. HLHS-variants and ventricular disproportion were excluded. RESULTS: 203 fetuses were identified with outcome information available for 201. There were extra-cardiac abnormalities in 8% (16/203), with genetic variants in 14% of those tested (17/122). There were 55 (27%) terminations of pregnancy, 5 (2%) intrauterine deaths and 10 (5%) babies had prenatally planned compassionate care. There was intention to treat (ITT) in the remaining 131/201(65%). Of these, there were 8 neonatal deaths before intervention, two patients had surgery in other centers. Of the other 121 patients, Norwood procedure performed in 113 (93%), initial hybrid in 7 (6%), and 1 had palliative coarctation stenting. Survival for the ITT group from birth at 6-months, 1-year and 5-years was 70%, 65%, 62% respectively. Altogether of the initial 201 prenatally diagnosed fetuses, 80 patients (40%) are currently alive. A restrictive atrial septum (RAS) is an important sub-category associated with death, HR 2.61, 95%CI 1.34-5.05, p = 0.005, with only 5/29 patients still alive. CONCLUSION: Medium-term outcomes of prenatally diagnosed HLHS have improved however it should be noted that almost 40% do not get to surgical palliation, which is vital to those doing fetal counselling. There remains significant mortality particularly in fetuses with in-utero diagnosed RAS.

Management of prenatally detected vascular rings: a United Kingdom national survey.

OBJECTIVE: To investigate UK variability in prenatal and postnatal management strategy of right aortic arch and double aortic arch (RAA/DAA). METHODS: Online surveys were sent to senior physicians (consultants) of the National Fetal Cardiology Working Group regarding prenatal diagnosis, counselling, and perinatal management of antenatally diagnosed RAA/DAA and to the British Congenital Cardiovascular Association regarding postnatal management strategies. RESULTS: There were 28 prenatal and 90 postnatal surveys completed. Prenatally, there was consensus for potential associated chromosomal/genetic anomalies, but there was variation in the risk quoted. Confidence in defining aortic arch morphology was reported by 43% (12/28) of fetal cardiologists. There was variation in what was felt to be possible symptoms/signs of a compressive vascular ring, postnatal investigation, postnatal management, follow-up duration of asymptomatic patients, and indications for surgical intervention. CONCLUSION: This study has highlighted important areas for future research: improving accuracy of prenatal diagnosis, clarification of potential symptoms, optimal investigation strategies, and indications for surgery.

Pulmonary artery banding: still a role for staged bi-ventricular repair of intracardiac shunts?

OBJECTIVES: Although pulmonary artery banding remains a useful palliation in bi-ventricular shunting lesions, single-stage repair holds several advantages. We investigate outcomes of the former approach in high-risk patients. METHODS: Retrospective cohort study including all pulmonary artery banding procedures over 9 years, excluding single ventricle physiology and left ventricular training. RESULTS: Banding was performed in 125 patients at a median age of 41 days (2-294) and weight of 3.4 kg (1.8-7.32). Staged repair was undertaken for significant co-morbidity in 81 (64.8%) and anatomical complexity in 44 (35.2%). The median hospital stay was 14 days (interquartile range 8-33.5) and 14 patients (11.2%) required anatomical repair before discharge. Nine patients died during the initial admission (hospital mortality 7.2 %) and five following discharge (inter-stage mortality 4.8%). Of 105 banded patients who survived, 19 (18.1%) needed inter-stage re-admission and 18 (14.4%) required unplanned re-intervention. Full repair was performed in 93 (74.4%) at a median age of 13 months (3.1-49.9) and weight of 8.5 kg (3.08-16.8). Prior banding, 54% were below the 0.4th weight centile, but only 28% remained so at repair. Post-repair, 5/93 (5.4%) developed heart block requiring permanent pacemaker, and 11/93 (11.8%) required unplanned re-intervention. The post-repair mortality (including repairs during the initial admission) was 6/93 (6.5%), with overall mortality of the staged approach 13.6% (17/125). CONCLUSIONS: In a cohort with a high incidence of co-morbidity, pulmonary artery banding is associated with a significant risk of re-intervention and mortality. Weight gain improves after banding, but heart block, re-intervention, and mortality remain frequent following repair.

Replacement dynamics and the pathogenesis of the Alpha, Delta and Omicron variants of SARS-CoV-2.

New SARS-CoV-2 variants causing COVID-19 are a major risk to public health worldwide due to the potential for phenotypic change and increases in pathogenicity, transmissibility and/or vaccine escape. Recognising signatures of new variants in terms of replacing growth and severity are key to informing the public health response. To assess this, we aimed to investigate key time periods in the course of infection, hospitalisation and death, by variant. We linked datasets on contact tracing (Contact Tracing Advisory Service), testing (the Second-Generation Surveillance System) and hospitalisation (the Admitted Patient Care dataset) for the entire length of contact tracing in the England - from March 2020 to March 2022. We modelled, for England, time delay distributions using a Bayesian doubly interval censored modelling approach for the SARS-CoV-2 variants Alpha, Delta, Delta Plus (AY.4.2), Omicron BA.1 and Omicron BA.2. This was conducted for the incubation period, the time from infection to hospitalisation and hospitalisation to death. We further modelled the growth of novel variant replacement using a generalised additive model with a negative binomial error structure and the relationship between incubation period length and the risk of a fatality using a Bernoulli generalised linear model with a logit link. The mean incubation periods for each variant were: Alpha 4.19 (95% credible interval (CrI) 4.13-4.26) days; Delta 3.87 (95% CrI 3.82-3.93) days; Delta Plus 3.92 (95% CrI 3.87-3.98) days; Omicron BA.1 3.67 (95% CrI 3.61-3.72) days and Omicron BA.2 3.48 (95% CrI 3.43-3.53) days. The mean time from infection to hospitalisation was for Alpha 11.31 (95% CrI 11.20-11.41) days, Delta 10.36 (95% CrI 10.26-10.45) days and Omicron BA.1 11.54 (95% CrI 11.38-11.70) days. The mean time from hospitalisation to death was, for Alpha 14.31 (95% CrI 14.00-14.62) days; Delta 12.81 (95% CrI 12.62-13.00) days and Omicron BA.2 16.02 (95% CrI 15.46-16.60) days. The 95th percentile of the incubation periods were: Alpha 11.19 (95% CrI 10.92-11.48) days; Delta 9.97 (95% CrI 9.73-10.21) days; Delta Plus 9.99 (95% CrI 9.78-10.24) days; Omicron BA.1 9.45 (95% CrI 9.23-9.67) days and Omicron BA.2 8.83 (95% CrI 8.62-9.05) days. Shorter incubation periods were associated with greater fatality risk when adjusted for age, sex, variant, vaccination status, vaccination manufacturer and time since last dose with an odds ratio of 0.83 (95% confidence interval 0.82-0.83) (P value < 0.05). Variants of SARS-CoV-2 that have replaced previously dominant variants have had shorter incubation periods. Conversely co-existing variants have had very similar and non-distinct incubation period distributions. Shorter incubation periods reflect generation time advantage, with a reduction in the time to the peak infectious period, and may be a significant factor in novel variant replacing growth. Shorter times for admission to hospital and death were associated with variant severity - the most severe variant, Delta, led to significantly earlier hospitalisation, and death. These measures are likely important for future risk assessment of new variants, and their potential impact on population health.

Electronic data collection, management and analysis tools used for outbreak response in low- and middle-income countries: a systematic review and stakeholder survey.

BACKGROUND: Use of electronic data collection, management and analysis tools to support outbreak response is limited, especially in low income countries. This can hamper timely decision-making during outbreak response. Identifying available tools and assessing their functions in the context of outbreak response would support appropriate selection and use, and likely more timely data-driven decision-making during outbreaks. METHODS: We conducted a systematic review and a stakeholder survey of the Global Outbreak Alert and Response Network and other partners to identify and describe the use of, and technical characteristics of, electronic data tools used for outbreak response in low- and middle-income countries. Databases included were MEDLINE, EMBASE, Global Health, Web of Science and CINAHL with publications related to tools for outbreak response included from January 2010-May 2020. Software tool websites of identified tools were also reviewed. Inclusion and exclusion criteria were applied and counts, and proportions of data obtained from the review or stakeholder survey were calculated. RESULTS: We identified 75 electronic tools including for data collection (33/75), management (13/75) and analysis (49/75) based on data from the review and survey. Twenty-eight tools integrated all three functionalities upon collection of additional information from the tool developer websites. The majority were open source, capable of offline data collection and data visualisation. EpiInfo, KoBoCollect and Open Data Kit had the broadest use, including for health promotion, infection prevention and control, and surveillance data capture. Survey participants highlighted harmonisation of data tools as a key challenge in outbreaks and the need for preparedness through training front-line responders on data tools. In partnership with the Global Health Network, we created an online interactive decision-making tool using data derived from the survey and review. CONCLUSIONS: Many electronic tools are available for data -collection, -management and -analysis in outbreak response, but appropriate tool selection depends on knowledge of tools' functionalities and capabilities. The online decision-making tool created to assist selection of the most appropriate tool(s) for outbreak response helps by matching requirements with functionality. Applying the tool together with harmonisation of data formats, and training of front-line responders outside of epidemic periods can support more timely data-driven decision making in outbreaks.

The Diagnostic Yield of Prenatal Genetic Technologies in Congenital Heart Disease: A Prospective Cohort Study.

INTRODUCTION: The objective was to evaluate: (i) the proportion of prenatally diagnosed congenital heart disease (CHD) associated with an abnormal quantitative fluorescence-PCR (QF-PCR), chromosome microarray (CMA), and exome sequencing (ES) result; and (ii) the diagnostic yield of these technologies based on CHD category and presence of extra-cardiac anomalies (ECAs). METHODS: This prospective cohort study was set across 12 UK foetal medicine centres. All cases underwent QF-PCR, CMA, and ES, and the diagnostic yield in n = 147 cases of prenatally diagnosed CHD was assessed. RESULTS: In 34.7% (n = 51/147), a genetic diagnosis was obtained. Using a stepwise testing strategy, the diagnostic yield for QF-PCR, CMA, and ES was 15.6% (n = 23/147), 13.7% (n = 17/124), and 10.2% (n = 11/107), respectively. Abnormal QF-PCR/shunt (septal) defects 31.4% (n = 11/35), p = 0.046, and abnormal CMA/conotruncal anomalies 22.7% (n = 10/44), p = 0.04, had significant associations. Monogenic variants were commonest in complex CHD 36.4% (n = 4/11). Multisystem CHD had a greater diagnostic yield overall compared to isolated OR 2.41 (95% CI, 1.1-5.1), particularly in association with brain and gastrointestinal tract anomalies. The proportion of variants of uncertain significance was 4.7% (n = 5/107) with ES, with none in the CMA group. CONCLUSION: In the era of prenatal ES, there remains an important role for QF-PCR and CMA. Identification of monogenic pathologic variants further allows delineation of prognosis in CHD.

Genomic Epidemiology of Complex, Multispecies, Plasmid-Borne blaKPC Carbapenemase in Enterobacterales in the United Kingdom from 2009 to 2014.

Carbapenem resistance in Enterobacterales is a public health threat. Klebsiella pneumoniae carbapenemase (encoded by alleles of the blaKPC family) is one of the most common transmissible carbapenem resistance mechanisms worldwide. The dissemination of blaKPC historically has been associated with distinct K. pneumoniae lineages (clonal group 258 [CG258]), a particular plasmid family (pKpQIL), and a composite transposon (Tn4401). In the United Kingdom, blaKPC has represented a large-scale, persistent management challenge for some hospitals, particularly in North West England. The dissemination of blaKPC has evolved to be polyclonal and polyspecies, but the genetic mechanisms underpinning this evolution have not been elucidated in detail; this study used short-read whole-genome sequencing of 604 blaKPC-positive isolates (Illumina) and long-read assembly (PacBio)/polishing (Illumina) of 21 isolates for characterization. We observed the dissemination of blaKPC (predominantly blaKPC-2; 573/604 [95%] isolates) across eight species and more than 100 known sequence types. Although there was some variation at the transposon level (mostly Tn4401a, 584/604 [97%] isolates; predominantly with ATTGA-ATTGA target site duplications, 465/604 [77%] isolates), blaKPC spread appears to have been supported by highly fluid, modular exchange of larger genetic segments among plasmid populations dominated by IncFIB (580/604 isolates), IncFII (545/604 isolates), and IncR (252/604 isolates) replicons. The subset of reconstructed plasmid sequences (21 isolates, 77 plasmids) also highlighted modular exchange among non-blaKPC and blaKPC plasmids and the common presence of multiple replicons within blaKPC plasmid structures (>60%). The substantial genomic plasticity observed has important implications for our understanding of the epidemiology of transmissible carbapenem resistance in Enterobacterales for the implementation of adequate surveillance approaches and for control.

Carriage and Acquisition of Extended-spectrum ß-Lactamase-producing Enterobacterales Among Neonates Admitted to Hospital in Kilifi, Kenya.

BACKGROUND: Infections caused by extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) among hospitalized neonates in sub-Saharan Africa pose significant clinical challenges. Data on prevalence and acquisition of ESBL-E carriage among hospitalized neonates in the region are few, and risk factors for transmission are not clearly defined. METHODS: In a cohort study of consecutive neonatal admissions to Kilifi County Hospital from July 2013 through August 2014, we estimated ESBL-E carriage prevalence on admission using rectal swab cultures and identified risk factors using logistic regression. Using twice-weekly follow-up swabs, we estimated the incidence and identified risk factors for ESBL-E acquisition in hospital using Poisson regression. RESULTS: The prevalence of ESBL-E carriage at admission was 10% (59/569). Cesarean delivery, older neonatal age, and smaller household size were significant risk factors. Of the 510 infants admitted without ESBL-E carriage, 238 (55%) acquired carriage during their hospital stay. The incidence of acquisition was 21.4% (95% confidence interval, 19.0%-24.0%) per day. The rate was positively associated with the number of known neonatal ESBL-E carriers and with the total number of neonates on the same ward. CONCLUSIONS: Carriage of ESBL-E was common among neonates on admission, and in-hospital acquisition was rapid. The dissemination and selection of ESBL-E appears to be driven by hospital exposures, operative delivery, and neonatal ward patient density. Further attention to infection control, patient crowding, and carriage surveillance is warranted.

Overview and Development of the Child Health and Mortality Prevention Surveillance Determination of Cause of Death (DeCoDe) Process and DeCoDe Diagnosis Standards.

Mortality surveillance and cause of death data are instrumental in improving health, identifying diseases and conditions that cause a high burden of preventable deaths, and allocating resources to prevent these deaths. The Child Health and Mortality Prevention Surveillance (CHAMPS) network uses a standardized process to define, assign, and code causes of stillbirth and child death (<5 years of age) across the CHAMPS network. A Determination of Cause of Death (DeCoDe) panel composed of experts from a local CHAMPS site analyzes all available individual information, including laboratory, histopathology, abstracted clinical records, and verbal autopsy findings for each case and, if applicable, also for the mother. Using this information, the site panel ascertains the underlying cause (event that precipitated the fatal sequence of events) and other antecedent, immediate, and maternal causes of death in accordance with the International Classification of Diseases, Tenth Revision and the World Health Organization death certificate. Development and use of the CHAMPS diagnosis standards-a framework of required evidence to support cause of death determination-assures a homogenized procedure leading to a more consistent interpretation of complex data across the CHAMPS network. This and other standardizations ensures future comparability with other sources of mortality data produced externally to this project. Early lessons learned from implementation of DeCoDe in 5 CHAMPS sites in sub-Saharan Africa and Bangladesh have been incorporated into the DeCoDe process, and the implementation of DeCoDe has the potential to spur health systems improvements and local public health action.

Mortality Surveillance Methods to Identify and Characterize Deaths in Child Health and Mortality Prevention Surveillance Network Sites.

Despite reductions over the past 2 decades, childhood mortality remains high in low- and middle-income countries in sub-Saharan Africa and South Asia. In these settings, children often die at home, without contact with the health system, and are neither accounted for, nor attributed with a cause of death. In addition, when cause of death determinations occur, they often use nonspecific methods. Consequently, findings from models currently utilized to build national and global estimates of causes of death are associated with substantial uncertainty. Higher-quality data would enable stakeholders to effectively target interventions for the leading causes of childhood mortality, a critical component to achieving the Sustainable Development Goals by eliminating preventable perinatal and childhood deaths. The Child Health and Mortality Prevention Surveillance (CHAMPS) Network tracks the causes of under-5 mortality and stillbirths at sites in sub-Saharan Africa and South Asia through comprehensive mortality surveillance, utilizing minimally invasive tissue sampling (MITS), postmortem laboratory and pathology testing, verbal autopsy, and clinical and demographic data. CHAMPS sites have established facility- and community-based mortality notification systems, which aim to report potentially eligible deaths, defined as under-5 deaths and stillbirths within a defined catchment area, within 24-36 hours so that MITS can be conducted quickly after death. Where MITS has been conducted, a final cause of death is determined by an expert review panel. Data on cause of death will be provided to local, national, and global stakeholders to inform strategies to reduce perinatal and childhood mortality in sub-Saharan Africa and South Asia.

Stenting and overdilating small Gore-Tex vascular grafts in complex congenital heart disease.

BACKGROUND: Gore-Tex® grafts are integral in the management of congenital heart disease. Issues of graft stenosis or somatic outgrowth may precipitate high-risk early surgery, and catheter intervention is a relatively under-reported management option. OBJECTIVES: To assess efficacy, safety, and outcomes of stenting and overdilating small Gore-Tex® vascular grafts with the aim of optimizing surgical timing. METHODS: Retrospective analysis of single-center, 13-year experience of 93 graft stenting interventions or reintervention in 80 patients, with the aim of relieving stenosis ± overdilation, to depose surgical graft revision or optimize surgical timing and candidacy. RESULTS: Median preintervention graft diameter was 52% (IQR 43-63) of nominal size, postintervention this increased to median 102% (IQR 96-120) [P < 0.001]. Overdilation was achieved in 54%; of these, the median final internal lumen was 126% (IQR 113-132) [P < 0.001]. Mean oxygen saturations increased from 69% to 82% [P < 0.001]. Adverse event rate was 14.9%; this includes mortality (3.2%) and atrioventricular conduction block (8.5%). Univariate analysis and logistic regression showed a significant relationship between adverse events and young age [P < 0.01], low weight [P < 0.01], univentricular physiology [P < 0.001], use of femoral venous access alone [P = 0.03], and intervention on a right ventricle to pulmonary artery conduit [P = 0.03]. Within respective indication groups, 74% were bridged to elective cavopulmonary shunt, 95% were bridged to biventricular surgery, and 78% of long-term palliative care patients continue under follow-up. CONCLUSIONS: Gore-Tex® vascular grafts can be stented effectively and expanded beyond nominal diameters by around +26%. This improves oxygen saturations, providing excellent palliation and optimized surgical timing. Adverse events are most frequent in precavopulmonary shunt patients. CONDENSED ABSTRACT: Gore-Tex® grafts are widely used in the palliation of cyanotic congenital heart disease. Grafts may become stenosed and do not allow for somatic growth. Over a 13 year period, graft stenting was performed in 80 patients (93 technically successful interventions, 4 unsuccessful.) Median internal lumen change was +50% (of nominal graft size), mean oxygen saturation change +13%. Over-dilation was performed in more than half of the cohort, with a median gain of +26% on nominal graft size. In precavopulmonary shunt patients, there was a moderate incidence of serious complications. Clinically useful deferral of surgery was achieved for the majority.

Stillbirth With Group B Streptococcus Disease Worldwide: Systematic Review and Meta-analyses.

BACKGROUND: There are an estimated 2.6 million stillbirths each year, many of which are due to infections, especially in low- and middle-income contexts. This paper, the eighth in a series on the burden of group B streptococcal (GBS) disease, aims to estimate the percentage of stillbirths associated with GBS disease. METHODS: We conducted systematic literature reviews (PubMed/Medline, Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde, World Health Organization Library Information System, and Scopus) and sought unpublished data from investigator groups. Studies were included if they reported original data on stillbirths (predominantly ≥28 weeks' gestation or ≥1000 g, with GBS isolated from a sterile site) as a percentage of total stillbirths. We did meta-analyses to derive pooled estimates of the percentage of GBS-associated stillbirths, regionally and worldwide for recent datasets. RESULTS: We included 14 studies from any period, 5 with recent data (after 2000). There were no data from Asia. We estimated that 1% (95% confidence interval [CI], 0-2%) of all stillbirths in developed countries and 4% (95% CI, 2%-6%) in Africa were associated with GBS. CONCLUSIONS: GBS is likely an important cause of stillbirth, especially in Africa. However, data are limited in terms of geographic spread, with no data from Asia, and cases worldwide are probably underestimated due to incomplete case ascertainment. More data, using standardized, systematic methods, are critical, particularly from low- and middle-income contexts where the highest burden of stillbirths occurs. These data are essential to inform interventions, such as maternal GBS vaccination.