Assessing the Effect of Data Quality on Distance Estimation in Smartphone-Based Outdoor 6MWT.

As a result of technological advancements, functional capacity assessments, such as the 6-minute walk test, can be performed remotely, at home and in the community. Current studies, however, tend to overlook the crucial aspect of data quality, often limiting their focus to idealised scenarios. Challenging conditions may arise when performing a test given the risk of collecting poor-quality GNSS signal, which can undermine the reliability of the results. This work shows the impact of applying filtering rules to avoid noisy samples in common algorithms that compute the walked distance from positioning data. Then, based on signal features, we assess the reliability of the distance estimation using logistic regression from the following two perspectives: error-based analysis, which relates to the estimated distance error, and user-based analysis, which distinguishes conventional from unconventional tests based on users' previous annotations. We highlight the impact of features associated with walked path irregularity and direction changes to establish data quality. We evaluate features within a binary classification task and reach an F1-score of 0.93 and an area under the curve of 0.97 for the user-based classification. Identifying unreliable tests is helpful to clinicians, who receive the recorded test results accompanied by quality assessments, and to patients, who can be given the opportunity to repeat tests classified as not following the instructions.

Risk assessment for aortic dissection in Turner syndrome: The role of the aortic growth rate.

OBJECTIVE: The risk of aortic dissection (AoD) is increased in Turner syndrome (TS) but predicting those at risk is difficult. Based on scarce evidence, preventive aortic surgery is recommended when aortic diameter increases >5 mm/year. To investigate the aortic growth rate in TS and TS-related conditions associated with aortic growth. We also reported our experience of women who suffered aortic dissection (AoD), and who had preventive aortic replacement. METHODS: 151 adult TS were retrospectively identified. Women who had more than one transthoracic echocardiogram (TTE) after age 16 years were included in the aortic growth study. Aortic diameters at sinuses of Valsalva (SoV) and ascending aorta (AA) were analysed by two experts. RESULTS: 70/151 women had more than one TTE (interscan interval 4.7 years). Mean aortic growth was 0.13 ± 0.59 mm/year at SoV and 0.23 ± 0.82 mm/year at AA. Known risk factors for aortic dilatation and TS-related conditions were not associated with aortic growth. 4/151 women experienced AoD (age 25±8 years): two had paired scans for aortic growth, which was 0.67 mm/year at both SoV and AA in the first woman, and 11 mm/year (SoV) and 4 mm/year (AA) in the second. Only 1/4 of women with AoD survived; she used a TS cardiac-alert card to inform emergency personnel about her risk of AoD. 5/151 had a preventive aortic replacement, but one died post-operatively. CONCLUSIONS: Mean aortic growth in our TS population was increased compared to non-TS women and was not associated with currently known risk factors for AoD, suggesting that aortic growth rate itself could be a useful variable to stratify who is at risk for AoD.

Analysis of a streamlined pathway for aortic surveillance for Turner syndrome in a single centre.

BACKGROUND AND OBJECTIVE: The risk of aortic dissection (AoD) is increased in women with Turner syndrome (TS) but predicting those with this heightened risk is difficult. In response to this, we sought to create a pathway to monitor TS patients to improve efficiency and resource utilisation in our dedicated TS clinic, and to monitor more closely those women thought to be at increased risk of AoD. DESIGN AND PATIENTS: Our pathway was designed based on evidence derived from International Guidelines for the management of aortic disease in women with TS. Women were divided according to those with known risk factors for AoD, and those with no known risk factors. These groups were further subdivided into 4 pathways depending on ascending aortic size which in-turn determined the frequency of outpatient appointments and imaging. RESULTS: Out of the 168 patients included in the analysis, 7 have had ascending aorta replacements, all in the highest risk group. Of the remaining 4 patients in the highest risk groups: 1 dissected whilst awaiting planned aortic surgery, 1 is currently awaiting surgery, 1 has low body mass index, therefore, making her aorta proportionally larger but not necessitating surgery and one has declined surgery. No women changed pathways. CONCLUSION: The risk-stratified pathway safely allowed consolidation of resources to women perceived to be at highest risk of AoD (excluding pregnancy), supporting the efficacy of the pathway and allowing the diversion of resources to those most at risk of AoD.

Direct current cardioversion in pregnancy: a multicentre study.

OBJECTIVE: Direct current cardioversion (DCCV) in pregnancy is rarely required and typically only documented in single case reports or case series. A recent UK confidential enquiry reported on several maternal deaths where appropriate DCCV appeared to have been withheld. DESIGN: Retrospective cohort study. SETTING: Seventeen UK and Ireland specialist maternity centres. SAMPLE: Twenty-seven pregnant women requiring DCCV in pregnancy. MAIN OUTCOME MEASURES: Maternal and fetal outcomes following DCCV. RESULTS: Twenty-seven women had a total of 29 DCCVs in pregnancy. Of these, 19 (70%) initial presentations were to Emergency Departments and eight (30%) to maternity settings. There were no maternal deaths. Seventeen of the women (63%) had a prior history of heart disease. Median gestation at DCCV was 28 weeks, median gestation at delivery was 35 weeks, with a live birth in all cases. The abnormal heart rhythms documented at the first cardioversion were atrial fibrillation in 12/27 (44%) cases, atrial flutter in 8/27 (30%), supraventricular tachycardia in 5/27 (19%) and atrial tachycardia in 2/27 (7%). Fetal monitoring was undertaken following DCCV on 14/29 (48%) occasions (10 of 19 (53%) at ≥26 weeks) and on 2/29 (7%) occasions, urgent delivery was required post DCCV. CONCLUSIONS: Direct current cardioversion in pregnancy is rarely required but should be undertaken when clinically indicated according to standard algorithms to optimise maternal wellbeing. Once the woman is stable post DCCV, gestation-relevant fetal monitoring should be undertaken. Maternity units should develop multidisciplinary processes to ensure pregnant women receive the same standard of care as their non-pregnant counterparts.

Tumour occurrence in women with Turner syndrome: A narrative review and single-centre case series.

BACKGROUND: Population studies suggest cancer morbidity may be different in Turner syndrome (TS) compared to the background female population. However, significant variability is observed in cancer associations likely due to heterogeneity in patient cohorts. We explored the prevalence and patterns of cancer amongst a cohort of women with TS attending a dedicated TS clinic. METHODS: Retrospective analysis of the patient database was performed to identify TS women who developed cancer. Population data (available before 2015) from the National Cancer Registration and Analysis Service database were used for comparison. RESULTS: Out of 156 TS women, median age of 32 (range 18-73) years, 9 (5.8%) had a recorded cancer diagnosis. Types of cancers were, bilateral gonadoblastoma, type 1 gastric neuroendocrine tumour (NET), appendiceal-NET, gastrointestinal stromal tumour, plasma cell dyscrasia, synovial sarcoma, cervical cancer, medulloblastoma and aplastic anaemia. Median age at cancer diagnosis was 35 (range 7-58) years and two were detected incidentally. Five women had 45,X karyotype, three received growth hormone treatment and all except one received oestrogen replacement therapy. The cancer prevalence of the background age-matched female population was 4.4%. CONCLUSIONS: We confirm the previous observations that women with TS do not appear to be at overall increased risk of common malignancies. Our small cohort showed a spectrum of rare malignancies that are not typically associated with TS, except for a single patient with a gonadoblastoma. The slightly higher prevalence of cancer in our cohort might simply represent increased cancer prevalence in the background population, or might be related to small sample size and regular monitoring of these women due to TS per se.

Acute vasodilator response testing in the adult Fontan circulation using non-invasive 4D Flow MRI: a proof-of-principle study.

BACKGROUND: Pulmonary vasodilator therapy in Fontan patients can improve exercise tolerance. We aimed to assess the potential for non-invasive testing of acute vasodilator response using four-dimensional (D) flow MRI during oxygen inhalation. MATERIALS AND METHODS: Six patients with well-functioning Fontan circulations were prospectively recruited and underwent cardiac MRI. Ventricular anatomical imaging and 4D Flow MRI were acquired at baseline and during inhalation of oxygen. Data were compared with six age-matched healthy volunteers with 4D Flow MRI scans acquired at baseline. RESULTS: All six patients tolerated the MRI scan well. The dominant ventricle had a left ventricular morphology in all cases. On 4D Flow MRI assessment, two patients (Patients 2 and 6) showed improved cardiac filling with improved preload during oxygen administration, increased mitral inflow, increased maximum E-wave kinetic energy, and decreased systolic peak kinetic energy. Patient 1 showed improved preload only. Patient 5 showed no change, and patient 3 had equivocal results. Patient 4, however, showed a decrease in preload and cardiac filling/function with oxygen. DISCUSSION: Using oxygen as a pulmonary vasodilator to assess increased pulmonary venous return as a marker for positive acute vasodilator response would provide pre-treatment assessment in a more physiological state - the awake patient. This proof-of-concept study showed that it is well tolerated and has shown changes in some stable patients with a Fontan circulation.

App-Based Versus Standard Six-Minute Walk Test in Pulmonary Hypertension: Mixed Methods Study.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a chronic disease of the pulmonary vasculature that can lead to heart failure and premature death. Assessment of patients with PAH includes performing a 6-minute walk test (6MWT) in clinics. We developed a smartphone app to compute the walked distance (6MWD) indoors, by counting U-turns, and outdoors, by using satellite positioning. OBJECTIVE: The goal of the research was to assess (1) accuracy of the indoor 6MWTs in clinical settings, (2) validity and test-retest reliability of outdoor 6MWTs in the community, (3) compliance, usability, and acceptance of the app, and (4) feasibility of pulse oximetry during 6MWTs. METHODS: We tested the app on 30 PAH patients over 6 months. Patients were asked to perform 3 conventional 6MWTs in clinic while using the app in the indoor mode and one or more app-based 6MWTs in outdoor mode in the community per month. RESULTS: Bland-Altman analysis of 70 pairs of conventional versus app-based indoor 6MWDs suggests that the app is sometimes inaccurate (14.6 m mean difference, lower and upper limit of agreement: -133.35 m to 162.55 m). The comparison of 69 pairs of conventional 6MWDs and community-based outdoor 6MWDs within 7 days shows that community tests are strongly related to those performed in clinic (correlation 0.89), but the interpretation of the distance should consider that differences above the clinically significant threshold are not uncommon. Analysis of 89 pairs of outdoor tests performed by the same patient within 7 days shows that community-based tests are repeatable (intraclass correlation 0.91, standard error of measurement 36.97 m, mean coefficient of variation 12.45%). Questionnaires and semistructured interviews indicate that the app is usable and well accepted, but motivation to use it could be affected if the data are not used for clinical decision, which may explain low compliance in 52% of our cohort. Analysis of pulse oximetry data indicates that conventional pulse oximeters are unreliable if used during a walk. CONCLUSIONS: App-based outdoor 6MWTs in community settings are valid, repeatable, and well accepted by patients. More studies would be needed to assess the benefits of using the app in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04633538; https://clinicaltrials.gov/ct2/show/NCT04633538.

Fertility issues and pregnancy outcomes in Turner syndrome.

OBJECTIVE: To study fertility issues and pregnancy outcomes in Turner syndrome (TS). DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): One hundred fifty-six TS patients, median age 32 years, 23 mosaic 45,X/46,XX, 45,X/47,XXX, 45,X/46,XX/47,XXX. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fertility choices, spontaneous pregnancy, and oocyte donation (OD) outcomes. Conditions associated with aortic dissection and poor pregnancy outcomes at preconception were considered. Pregnancy-related aortic dimension changes and the long-term impact of pregnancy on TS-related comorbidities were assessed. RESULTS(S): In all, 13.5% had spontaneous pregnancies, resulting in a pregnancy with live birth in 18 patients (37 newborns); 16% considered OD, one adopted, and one underwent fertility preservation. Spontaneous pregnancy predictive factors were a karyotype with a second or third cell line with more than one X and spontaneous menarche. In all, 47.6% had miscarriages, two experienced preeclampsia, and two had gestational diabetes. One daughter was diagnosed with TS in adulthood. Seven of 14 who attempted OD had a pregnancy with live birth; two of seven had gestational diabetes; 64.3% attempting OD had risk factors associated with poor pregnancy outcomes, including four who had double embryo transfer. Cardiac status at preconception was evaluated in 12 of 25 women who had a pregnancy. The aortic diameters during pregnancy increased. The aortic growth at sinuses was 0.51 ± 0.71 mm/year and at ascending aorta 0.67 ± 0.67 mm/year, reaching a significant difference at sinuses compared with the growth in nulliparous TS. Among women who had a pregnancy, none experienced aortic dissection during and in the years after pregnancy. CONCLUSION(S): This study highlights the importance of a TS-dedicated multidisciplinary management of pregnancy, before and during pregnancy and in the postpartum period.

The Mobile-Based 6-Minute Walk Test: Usability Study and Algorithm Development and Validation.

BACKGROUND: The 6-min walk test (6MWT) is a convenient method for assessing functional capacity in patients with cardiopulmonary conditions. It is usually performed in the context of a hospital clinic and thus requires the involvement of hospital staff and facilities, with their associated costs. OBJECTIVE: This study aimed to develop a mobile phone-based system that allows patients to perform the 6MWT in the community. METHODS: We developed 2 algorithms to compute the distance walked during a 6MWT using sensors embedded in a mobile phone. One algorithm makes use of the global positioning system to track the location of the phone when outdoors and hence computes the distance travelled. The other algorithm is meant to be used indoors and exploits the inertial sensors built into the phone to detect U-turns when patients walk back and forth along a corridor of fixed length. We included these algorithms in a mobile phone app, integrated with wireless pulse oximeters and a back-end server. We performed Bland-Altman analysis of the difference between the distances estimated by the phone and by a reference trundle wheel on 49 indoor tests and 30 outdoor tests, with 11 different mobile phones (both Apple iOS and Google Android operating systems). We also assessed usability aspects related to the app in a discussion group with patients and clinicians using a technology acceptance model to guide discussion. RESULTS: The mean difference between the mobile phone-estimated distances and the reference values was -2.013 m (SD 7.84 m) for the indoor algorithm and -0.80 m (SD 18.56 m) for the outdoor algorithm. The absolute maximum difference was, in both cases, below the clinically significant threshold. A total of 2 pulmonary hypertension patients, 1 cardiologist, 2 physiologists, and 1 nurse took part in the discussion group, where issues arising from the use of the 6MWT in hospital were identified. The app was demonstrated to be usable, and the 2 patients were keen to use it in the long term. CONCLUSIONS: The system described in this paper allows patients to perform the 6MWT at a place of their convenience. In addition, the use of pulse oximetry allows more information to be generated about the patient's health status and, possibly, be more relevant to the real-life impact of their condition. Preliminary assessment has shown that the developed 6MWT app is highly accurate and well accepted by its users. Further tests are needed to assess its clinical value.

Ascending aortic dissection in a pregnant patient with neonatally repaired coarctation of aorta and bicuspid aortic valve.

Aortic dissection is characterised by a tear in the intimal and medial layers of the endovascular aortic wall which propagates distally. Here, we discuss the case of a 35-year-old woman who was 37 weeks pregnant and presented with dizziness and blurred vision. She had a history of a neonatal end-to-end repair of a coarctation of aorta, a known bicuspid aortic valve and a dilated ascending aorta under surveillance. A transthoracic echocardiogram revealed an ascending aortic dissection. An emergency CT aortogram was performed which confirmed the diagnosis. The patient underwent emergency caesarean section and aortic surgery, with a good outcome for mother and baby. The case highlights the atypical nature of presentation and the absence of haemodynamic instability. Atypical and unexplained symptoms on a background of congenital heart disease should trigger a referral to cardiology with thorough investigation, often with echocardiography, to exclude rare and life-threatening complications.

Differential flow improvements after valve replacements in bicuspid aortic valve disease: a cardiovascular magnetic resonance assessment.

BACKGROUND: Abnormal aortic flow patterns in bicuspid aortic valve disease (BAV) may be partly responsible for the associated aortic dilation. Aortic valve replacement (AVR) may normalize flow patterns and potentially slow the concomitant aortic dilation. We therefore sought to examine differences in flow patterns post AVR. METHODS: Ninety participants underwent 4D flow cardiovascular magnetic resonance: 30 BAV patients with prior AVR (11 mechanical, 10 bioprosthetic, 9 Ross procedure), 30 BAV patients with a native aortic valve and 30 healthy subjects. RESULTS: The majority of subjects with mechanical AVR or Ross showed normal flow pattern (73% and 67% respectively) with near normal rotational flow values (7.2 ± 3.9 and 10.6 ± 10.5 mm2/ms respectively vs 3.8 ± 3.1 mm2/s for healthy subjects; both p > 0.05); and reduced in-plane wall shear stress (0.19 ± 0.13 N/m2 for mechanical AVR vs. 0.40 ± 0.28 N/m2 for native BAV, p < 0.05). In contrast, all subjects with a bioprosthetic AVR had abnormal flow patterns (mainly marked right-handed helical flow), with comparable rotational flow values to native BAV (20.7 ± 8.8 mm2/ms and 26.6 ± 16.6 mm2/ms respectively, p > 0.05), and a similar pattern for wall shear stress. Data before and after AVR (n = 16) supported these findings: mechanical AVR showed a significant reduction in rotational flow (30.4 ± 16.3 → 7.3 ± 4.1 mm2/ms; p < 0.05) and in-plane wall shear stress (0.47 ± 0.20 → 0.20 ± 0.13 N/m2; p < 0.05), whereas these parameters remained similar in the bioprosthetic AVR group. CONCLUSIONS: Abnormal flow patterns in BAV disease tend to normalize after mechanical AVR or Ross procedure, in contrast to the remnant abnormal flow pattern after bioprosthetic AVR. This may in part explain different aortic growth rates post AVR in BAV observed in the literature, but requires confirmation in a prospective study.

Lipid production in Nannochloropsis gaditana is doubled by decreasing expression of a single transcriptional regulator.

Lipid production in the industrial microalga Nannochloropsis gaditana exceeds that of model algal species and can be maximized by nutrient starvation in batch culture. However, starvation halts growth, thereby decreasing productivity. Efforts to engineer N. gaditana strains that can accumulate biomass and overproduce lipids have previously met with little success. We identified 20 transcription factors as putative negative regulators of lipid production by using RNA-seq analysis of N. gaditana during nitrogen deprivation. Application of a CRISPR-Cas9 reverse-genetics pipeline enabled insertional mutagenesis of 18 of these 20 transcription factors. Knocking out a homolog of fungal Zn(II)2Cys6-encoding genes improved partitioning of total carbon to lipids from 20% (wild type) to 40-55% (mutant) in nutrient-replete conditions. Knockout mutants grew poorly, but attenuation of Zn(II)2Cys6 expression yielded strains producing twice as much lipid (∼5.0 g m-2 d-1) as that in the wild type (∼2.5 g m-2 d-1) under semicontinuous growth conditions and had little effect on growth.

Fungal myocarditis in a preterm neonate.

A male infant born at 25 weeks gestation presented with abdominal distension, was transferred to our institution for surgical management following suspected bowel perforation with severe sepsis. Umbilical catheter cultures grew Candida parapsilosis. At laparotomy, there was a large ileal perforation with peritonitis, he was treated with amphotericin, antibiotics and had an ileostomy. He had persistent pulmonary hypertension, requiring nitric oxide and high-frequency oscillatory ventilation. Serial echocardiograms revealed a patent ductus arteriosus (PDA), but also demonstrated increasing left ventricular hypertrophy and the development of bright areas within the septal myocardium. Further bright areas developed over a course of 2 weeks in his right ventricular outflow tract. After treatment for candidal infection, there was improvement in left ventricular thickness and brightness of the echogenic lesions was reduced. Biopsy of the lesions was discounted due to the risk of the procedure, the size of the infant and his improving clinical status.