Hickscraig9618

Technical advancements in 2D-speckle tracking echocardiography (2DSTE) have allowed for quantification of layer-specific global longitudinal strain (GLS) and circumferential strain (GCS) of the left ventricle (LV). The aim of this study was to establish age- and sex-based reference ranges of peak systolic layer-specific GLS and GCS and to assess normal values of regional strain.

We performed 2DSTE analysis of 1997 members of the general population from the fifth round of the Copenhagen City Heart Study, who were free of cardiovascular disease and risk factors. The mean age was 46 ± 16 years (range 21-97) and 62% were female. Mean values for peak systolic whole wall GLS (GLSWW.Sys), endomycardial (GLSEndo.Sys), and epimyocardial (GLSEpi.Sys) were 19.9 ± 2.1% (prediction interval [PI] 15.8-24.0%), 23.5 ± 2.5% (PI 18.6-28.4%), and 17.3 ± 1.9% (PI 13.6-21.1%), respectively. Mean peak systolic whole wall GCS (GCSWW.Sys), was 21.6 ± 3.7% (PI 14.3-28.9%), endomyocardial (GCSEndo.Sys) was 31.9 ± 4.7% (PI 22.7-41.1%), and epimyocardial (GCSEpi.Sys) was 14.3 ± 3.8% (PI 6.8-21.8%). A significant discrepancy in normal strain values between males and females was observed. Men had lower mean values and lower reference limits for all strain parameters. Furthermore, GLS and GCS changed differently with age in males and females. Finally, regional LS decreased from the apical to the basal LV region in both sexes, and regional CS varied significantly by LV segment.

In this study, we reported age- and sex-based reference ranges of layer-specific GLS and GCS. These reference ranges varied significantly with sex and age.

In this study, we reported age- and sex-based reference ranges of layer-specific GLS and GCS. These reference ranges varied significantly with sex and age.

Central nervous system involvement is present in 70% of patients with hemophagocytic lymphohistiocytosis (CNS-HLH). CNS-HLH is defined by neurologic deficits, neuroimaging abnormalities, or positive cerebrospinal fluid (CSF) findings. The CSF cytomorphologic spectrum of CNS-HLH, however, has not been well investigated.

A retrospective review was performed on 64 CSF specimens from pediatric and adult patients with HLH. Ten patients had clinicoradiologic evidence of CNS involvement.

We identified five CSF cytomorphologic patterns (1) hemophagocytosis, (2) vacuolated macrophages without evidence of hemophagocytosis, (3) monocytes and/or nonvacuolated macrophages, (4) acellular specimens, and (5) bloody specimens. Patterns 1 and 2 were common in CNS-HLH and rare in patients without CNS involvement. The CSF cytomorphologic patterns did not correlate well with WBC counts or protein concentration.

Our study offers a comprehensive view of the cytomorphologic features seen in CSF specimens from patients with HLH.

Our study offers a comprehensive view of the cytomorphologic features seen in CSF specimens from patients with HLH.

On 13 March 2020, the Danish authorities imposed extensive nationwide lockdown measures to prevent the spread of the coronavirus disease 2019 (COVID-19) and reallocated limited healthcare resources. We investigated mortality rates, overall and according to location, in patients with established cardiovascular disease before, during, and after these lockdown measures.

Using Danish nationwide registries, we identified a dynamic cohort comprising all Danish citizens with cardiovascular disease (i.e. a history of ischaemic heart disease, ischaemic stroke, heart failure, atrial fibrillation, or peripheral artery disease) alive on 2 January 2019 and 2020. The cohort was followed from 2 January 2019/2020 until death or 16/15 October 2019/2020. The cohort comprised 340 392 and 347 136 patients with cardiovascular disease in 2019 and 2020, respectively. The overall, in-hospital, and out-of-hospital mortality rate in 2020 before lockdown was significantly lower compared with the same period in 2019 [adjusted inciden the preceding year, irrespective of age and sex.To assess the prevalence of persistent functional impairment after coronavirus disease (COVID-19), we assessed 118 individuals 3-4 months after their initial COVID-19 diagnosis with a symptom survey, work productivity and activity index questionnaire, and 6-minute walk test. We found significant persistent symptoms and functional impairment, even in non-hospitalized patients with COVID-19.

In patients with active cancer and atrial fibrillation (AF) anticoagulation, thrombotic and bleeding risk still entail uncertainty.

We explored the results of an international survey examining the knowledge and behaviours of a large group of physicians.

A web-based survey was completed by 960 physicians (82.4% cardiologists, 75.5% from Europe). Among the currently available anticoagulants for stroke prevention in patients with active cancer, direct oral anticoagulants (DOACs) were preferred by 62.6%, with lower values for low molecular weight heparin (LMWH) (24.1%) and for warfarin (only 7.3%). About 46% of respondents considered that DOACs should be used in all types of cancers except in non-operable gastrointestinal cancers. The lack of controlled studies on bleeding risk (33.5% of respondents) and the risk of drug interactions (31.5%) were perceived as problematic issues associated with use of anticoagulants in cancer. The decision on anticoagulation involved a cardiologist in 27.8% of cases, a cardiologist and an oncologist in 41.1%, and a team approach in 21.6%. The patient also was involved in decision-making, according to ∼60% of the respondents. For risk stratification, use of CHA2DS2-VASc and HAS-BLED scores was considered appropriate, although not specifically validated in cancer patients, by 66.7% and 56.4%, respectively.

This survey highlights that management of anticoagulation in patients with AF and active cancer is challenging, with substantial heterogeneity in therapeutic choices. Direct oral anticoagulants seems having an emerging role but still the use of LMWH remains substantial, despite the absence of long-term data on thromboprophylaxis in AF.

This survey highlights that management of anticoagulation in patients with AF and active cancer is challenging, with substantial heterogeneity in therapeutic choices. Direct oral anticoagulants seems having an emerging role but still the use of LMWH remains substantial, despite the absence of long-term data on thromboprophylaxis in AF.

The impact of hypothermic circulatory arrest (HCA) temperature on postoperative acute kidney injury (AKI) has not been evaluated. This study examined the association between circulatory arrest temperatures and AKI in patients undergoing proximal aortic surgery with HCA.

A total of 759 consecutive patients who underwent proximal aortic surgery (ascending ± valve ± root) including arch replacement requiring HCA between July 2005 and December 2016 were identified from a prospectively maintained institutional aortic surgery database. The primary outcome was AKI as defined by Risk, Injury, Failure, Loss, End Stage Renal Disease (ESRD) criteria. The association between minimum nasopharyngeal (NP) and bladder temperatures during HCA and postoperative AKI was assessed, adjusting for patient-level factors using multivariable logistic regression.

A total of 85% (n = 645) of patients underwent deep hypothermia (14.1-20.0°C), 11% (n = 83) low-moderate hypothermia (20.1-24.0°C) and 4% (n = 31) high-moderate hypothergoing proximal aortic surgery including arch replacement requiring HCA, degree of systemic hypothermia was not associated with the risk of AKI. These data suggest that moderate hypothermia does not confer increased risk of AKI for patients requiring circulatory arrest, although additional prospective data are needed.

Patients with coronary heart disease (CHD) are at very high risk of recurrent events. A strategy to reduce excess risk might be to deliver structured secondary prevention programmes, but their efficacy has been mostly evaluated in the short term and in experimental settings. This is a retrospective case-control study aimed at assessing, in the real world, the efficacy of a secondary prevention programme in reducing long-term coronary event recurrences after coronary artery bypass surgery (CABG).

Programme participants (henceforth 'cases') were men and women aged <75 years subjected to CABG between 2002 and 2014, living within 100 km of the hospital. Key programme actions included optimization of treatments according to the most updated European preventive guidelines, surveillance of therapy adherence, and customized lifestyle counselling. Controls were analogous patients not involved in the programme because living farther than 100 km away, matched 11 with cases for gender, age at CABG, and year of CABG. Both groups (n = 1248) underwent usual periodic cardiology follow-up at our centre. Data on symptomatic or silent CHD recurrences were obtained from the hospital electronic health records. Cox analysis (adjusted for baseline differences between groups) shows that programme participation was associated with a significantly lower incidence throughout 5 years post-CABG of symptomatic [hazard ratio (95% confidence interval) 0.59 (0.38-0.94)] and silent [0.53 (0.31-0.89)] coronary recurrences.

In a real-world setting, taking part in a structured longstanding secondary prevention programme, in addition to usual cardiology care, meaningfully lowers the risk of coronary recurrences.

In a real-world setting, taking part in a structured longstanding secondary prevention programme, in addition to usual cardiology care, meaningfully lowers the risk of coronary recurrences.

To explore the feasibility of upper limbs cardiopulmonary exercise test (CPET) in Friedreich ataxia (FRDA) patients and to compare the results with sex, age, and body mass index (BMI) matched cohort of healthy controls (HC).

Cardiopulmonary exercise test was performed using an upper limbs cycle ergometer on fasting subjects. Peak oxygen uptake (peak VO2) was recorded as the mean value of VO2 during a 20 s period at the maximal effort of the test at an appropriate respiratory exchange rate. The ventilatory anaerobic threshold (AT) was detected by the use of the V-slope method. We performed echocardiography with an ultrasound system equipped with a 2.5 MHz multifrequency transducer for complete M-mode, two-dimensional, Doppler, and Tissue Doppler Imaging analyses. We studied 55 FRDA and 54 healthy matched controls (HC). Peak VO2 showed a significant 31% reduction in FRDA patients compared to HC (15.2 ± 5.7 vs. 22.0 ± 6.1 mL/kg/min; P < 0.001). Peak workload was reduced by 41% in FRDA (42.9 ± 12.5 vs. 73.1 ± 21.2 W; P < 0.001). In FRDA patients, peak VO2 is inversely correlated with the Scale for Assessment and Rating of Ataxia score, disease duration, and 9HPT performance, and directly correlated with activities of daily living. The AT occurred at 48% of peak workload time in FRDA patients and at 85% in HC (P < 0.001).

Upper limb CPET is useful in the assessment of exercise tolerance and a possible tool to determine the functional severity of the mitochondrial oxidative defect in patients with FRDA. The cardiopulmonary exercise test is an ideal functional endpoint for Phases II and III trials through a simple, non-invasive, and safe exercise test.

Upper limb CPET is useful in the assessment of exercise tolerance and a possible tool to determine the functional severity of the mitochondrial oxidative defect in patients with FRDA. The cardiopulmonary exercise test is an ideal functional endpoint for Phases II and III trials through a simple, non-invasive, and safe exercise test.

Most patients with established atherosclerotic cardiovascular disease (CVD) are at very high risk for developing recurrent events. Since this risk varies a lot between patients there is a need to identify those in whom an even more intensive secondary prevention strategy should be envisaged. Using data from the EUROASPIRE IV and V cohorts of coronary heart disease (CHD) patients from 27 European countries, we aimed at developing and internally and externally validating a risk model predicting recurrent CVD events in patients aged < 75 years.

Prospective data were available for 12484 patients after a median follow-up time of 1.7 years. The primary endpoint, a composite of fatal CVD or new hospitalizations for non-fatal myocardial infarction (MI), stroke, heart failure, coronary artery bypass graft, or percutaneous coronary intervention (PCI), occurred in 1424 patients. The model was developed based on data from 8000 randomly selected patients in whom the association between potential risk factors and thn order to prevent further disease or death. The EUROASPIRE Risk Calculator may be of help to reach this goal.

In patients with CHD, fatal and non-fatal rates of recurrent CVD events are high. However, there are still opportunities to optimize their management in order to prevent further disease or death. The EUROASPIRE Risk Calculator may be of help to reach this goal.

To study the pathologic spectrum of kidney diseases in patients with hepatitis C virus infection (HCV+).

Native kidney biopsy specimens in HCV+ patients were reviewed.

A total of 9,836 native kidney biopsy specimens were evaluated from January 2007 to December 2016, of which 273 (2.8%) were from HCV+ patients, and of these, 115 (42.1%) had diagnoses consistent with HCV-associated glomerulonephritis (GN). Non-HCV-associated kidney diseases comprised most diagnoses (158 cases, 57.9%) including non-immune complex-mediated kidney diseases (127 cases, 46.5%) and other immune complex-mediated glomerular diseases (31 cases, 11.4%). Forty-one (40.6%) patients had HCV-associated GN among 101 HCV+ patients from 2007 to 2011 vs 74 (43.0%) patients with HCV-associated GN among 172 HCV+ patients from 2012 to 2016. HCV-associated GN showed five morphologic patterns focal proliferative (5.2%), diffuse mesangial proliferative (50.4%), diffuse membranoproliferative (28.7%), proliferative GN with crescentic lesions (7.8%), and membranous patterns (7.8%).

We found a spectrum of pathologic changes in renal biopsy specimens of HCV+ patients, with most having diseases unrelated to HCV infection, HCV-associated GN showing five morphologic patterns, and availability of effective HCV antiviral therapy not yet resulting in major changes in the spectrum of kidney diseases in these patients.

We found a spectrum of pathologic changes in renal biopsy specimens of HCV+ patients, with most having diseases unrelated to HCV infection, HCV-associated GN showing five morphologic patterns, and availability of effective HCV antiviral therapy not yet resulting in major changes in the spectrum of kidney diseases in these patients.Coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic by the World Health Organization, and the situation worsens daily, associated with acute increases in case fatality rates. The main protease (Mpro) enzyme produced by SARS-CoV-2 was recently demonstrated to be responsible for not only viral reproduction but also impeding host immune responses. The element selenium (Se) plays a vital role in immune functions, both directly and indirectly. Thus, we hypothesised that Se-containing heterocyclic compounds might curb the activity of SARS-CoV-2 Mpro. We performed a molecular docking analysis and found that several of the selected selenocompounds showed potential binding affinities for SARS-CoV-2 Mpro, especially ethaselen (49), which exhibited a docking score of -6.7 kcal/mol compared with the -6.5 kcal/mol score for GC376 (positive control). Drug-likeness calculations suggested that these compounds are biologically active and possess the characteristics of ideal drug candidates. Based on the binding affinity and drug-likeness results, we selected the 16 most effective selenocompounds as potential anti-COVID-19 drug candidates. We also validated the structural integrity and stability of the drug candidate through molecular dynamics simulation. Using further in vitro and in vivo experiments, we believe that the targeted compound identified in this study (ethaselen) could pave the way for the development of prospective drugs to combat SARS-CoV-2 infections and trigger specific host immune responses.The incidence of malignant melanoma, a neoplasm of melanocytic cells, is increasing rapidly. The lymph nodes are often the first site of metastasis and can herald systemic dissemination, which is almost uniformly fatal. RLIP, a multi-specific ATP-dependent transporter that is over-expressed in several types of cancers, plays a central role in cancer cell resistance to radiation and chemotherapy. RLIP appears to be necessary for cancer cell survival because both in vitro cell culture and in vivo animal tumor studies show that the depletion or inhibition of RLIP causes selective toxicity to malignant cells. RLIP depletion/inhibition triggers apoptosis in cancer cells by inducing the accumulation of endogenously formed glutathione-conjugates. In our in vivo studies, we administered RLIP antibodies or antisense oligonucleotides to mice bearing subcutaneous xenografts of SKMEL2 and SKMEL5 melanoma cells and demonstrated that both treatments caused significant xenograft regression with no apparent toxic effects. Anti-RLIP antibodies and antisense, which respectively inhibit RLIP-mediated transport and deplete RLIP expression, showed similar tumor regressing activities, indicating that the inhibition of RLIP transport activity at the cell surface is sufficient to achieve anti-tumor activity. Furthermore, RLIP antisense treatment reduced levels of RLIP, pSTAT3, pJAK2, pSrc, Mcl-1 and Bcl2, as well as CDK4 and cyclin B1, and increased levels of Bax and phospho 5' AMP-activated protein kinase (pAMPK). These studies indicate that RLIP serves as a key effector in the survival of melanoma cells and is a valid target for cancer therapy. Overall, compounds that inhibit, deplete or downregulate RLIP will function as wide-spectrum agents to treat melanoma, independent of common signaling pathway mutations.

To examine trends in ischaemic heart disease (IHD) incidence and prevalence in New Zealand from 2005 to 2016, using comprehensive linked national hospitalization and mortality data as proxy measures of all significant events.

Incident and prevalent cases of IHD in people aged ≥25 years were identified using individual patient-linkage of routinely collected ICD-10-coded hospitalization and mortality data. Incidence rates and prevalence proportions were calculated by sex and age group and then age-standardized to the 2016 New Zealand population. Ischaemic heart disease incidence and prevalence declined in men and women in all age groups. The average annual rate of decline in age-standardized IHD incidence was 3.3% for women and 2.7% for men, and the rate of decline in age-standardized IHD prevalence was 3.2% for women and 2.2% for men. Despite a 17% increase in the New Zealand population aged 25 years and over during the study period, the total number of people living with IHD also decreased, particularly in those aged 65 years and older.

In contrast to observations from other countries, where IHD incidence but not IHD prevalence has been falling, declining IHD incidence in New Zealand in recent decades is now mirrored by declining IHD prevalence.

In contrast to observations from other countries, where IHD incidence but not IHD prevalence has been falling, declining IHD incidence in New Zealand in recent decades is now mirrored by declining IHD prevalence.Cardiomyopathies (CMPs) are primary disorders of myocardial structure and function in the absence of coronary artery disease, hypertension, valvular disease, and congenital heart disease. Knowledge of the incidence and prevalence of CMPs may help clinicians to compare their observations in clinical practice with expected cases per person-year and to avoid under-reporting in clinical context. Currently, available estimates of prevalence and incidence of CMPs are based on clinical data, collected with a wide variability in population-source, and before the genetic testing evolved as a standard diagnostic tool. This review focuses on the epidemiology of CMPs in subjects aged between 18 and 55 years. A structured up-to-date diagnostic flow-chart for CMPs diagnosis and assessment is proposed to avoid misdiagnosis of CMPs in the young population and in subjects with unexplained cardiac disorders.

Antimicrobial resistance is a serious global health concern that emphasizes completing treatment course. Recently, the effectiveness of short versus longer antibiotic courses has been questioned. This study investigated the duration of prescribed antibiotics, their effectiveness, and associated risk of infection-related complications.

Clinical Practice Research Datalink identified 4 million acute infection episodes prescribed an antibiotic in primary care between January 2014-June 2014, England. Prescriptions were categorized by duration. Risk of infection-related hospitalizations within 30 days was modelled overall and by infection type. Risk was assessed immediately after or within 30 days follow-up to measure confounders given similar and varying exposure, respectively. An interaction term with follow-up time assessed whether hazard ratios (HRs) remained parallel with different antibiotic durations.

The duration of antibiotic courses increased over the study period (5.2-19.1%); 6-7 days were most comonger courses were no more effective than shorter courses.

Equal effectiveness was found between shorter and longer antibiotic courses and the reduction of infection-related hospitalizations. Stewardship programs should recommend shorter courses of antibiotics for acute infections. Further research is required for treating patients with a complex medical history.SummaryPrescribing of longer courses increased over the study period. The majority of hospitalizations occurred for patients receiving longer courses. Risk of developing a complication (immediate vs remaining follow-up) found longer courses were no more effective than shorter courses.Lentivector gene therapy for X-linked chronic granulomatous disease (X-CGD) has proven to be a viable approach, but random vector integration and subnormal protein production from exogenous promoters in transduced cells remain concerning for long-term safety and efficacy. A previous genome editing-based approach using Streptococcus pyogenes Cas9 mRNA and an oligodeoxynucleotide donor to repair genetic mutations showed the capability to restore physiological protein expression but lacked sufficient efficiency in quiescent CD34+ hematopoietic cells for clinical translation. Here, we report that transient inhibition of p53-binding protein 1 (53BP1) significantly increased (2.3-fold) long-term homology-directed repair to achieve highly efficient (80% gp91phox+ cells compared with healthy donor control subjects) long-term correction of X-CGD CD34+ cells.

Deep sternal wound infection (DSWI) is a serious complication after open-heart surgery. We investigated the association between DSWI and short- and long-term all-cause mortality in a large well-defined nationwide population.

A retrospective, nationwide cohort study, which included 114676 consecutive patients who underwent coronary artery bypass grafting (CABG) and/or valve surgery from 1997 to 2015 in Sweden. Short- and long-term mortality was compared between DSWI patients and non-DSWI patients using propensity score inverse probability weighting adjustment based on patient characteristics and comorbidities. Median follow-up was 8.0 years (range 0-18.9).

Altogether, 1516 patients (1.3%) developed DSWI, most commonly in patients undergoing combined CABG and valve surgery (2.1%). DSWI patients were older and had more disease burden than non-DSWI patients. The unadjusted cumulative mortality was higher in the DSWI group compared with the non-DSWI group at 90 days (7.9% vs 3.0%, P < 0.001) and at 1 year (12.8% vs 4.5%, P < 0.001). The adjusted absolute difference in risk of death was 2.3% [95% confidence interval (CI) 0.8-3.9] at 90 days and 4.7% (95% CI 2.6-6.7) at 1 year. DSWI was independently associated with 90-day [adjusted relative risk (aRR) 1.89 (95% CI 1.38-2.59)], 1-year [aRR 2.13 (95% CI 1.68-2.71)] and long-term all-cause mortality [adjusted hazard ratio 1.56 (95% CI 1.30-1.88)].

Both short- and long-term mortality risks are higher in DSWI patients compared to non-DSWI patients. These results stress the importance of preventing these infections and careful postoperative monitoring of DSWI patients.

Both short- and long-term mortality risks are higher in DSWI patients compared to non-DSWI patients. These results stress the importance of preventing these infections and careful postoperative monitoring of DSWI patients.We investigated the association of cumulative socioeconomic disadvantage (CSD) and socioeconomic (SES) trajectories across life course with the risk of first hospitalization for heart failure (HF) or atrial fibrillation (AF) and tested some biological mechanisms in explaining such associations. Longitudinal analysis on 21,756 HF- and AF-free subjects recruited in the Moli-sani Study (2005-2010; Italy) and followed up for 8.2 years. CSD was computed using childhood SES, education and adulthood SES indicators, and the same were used to define overall trajectories. High disadvantage across life course (CSD≥8) posed subjects at increased risk of HF (Hazard ratio [HR]=2.58; 95%CI 1.78, 3.74) or AF (HR=1.57;1.05,2.33), as compared to low CSD. All explanatory factors accounted for 18.5% and 24% of the excess of HF and AF risks, respectively, associated with CSD. For subjects with low childhood SES, advancements in education lowered risk of HF (HR=0.70;0.48, 1.02) or AF (HR=0.50;0.28, 0.89), whereas achievements of adulthood SES were unlikely to contribute to disease reduction. In conclusion, a life-course disadvantaged SES is an important predictor of first hospitalization for HF and AF; known risk factors partially explained the SES-disease gradient. Upwardly mobile groups are likely to mitigate the effect of poor childhood circumstances especially through educational advancement.

Type 2 diabetes mellitus (T2DM) is associated with reduced exercise capacity and cardiovascular diseases, both increasing morbidity and risk for premature death. As exercise intolerance often relates to cardiac dysfunction, it remains to be elucidated to what extent such an interplay occurs in T2DM patients without overt cardiovascular diseases. Design Cross-sectional study, NCT03299790.

Fifty-three T2DM patients underwent exercise echocardiography (semi-supine bicycle) with combined ergospirometry. Cardiac output (CO), left ventricular longitudinal strain (LS), oxygen uptake (O2), and oxygen (O2) extraction were assessed simultaneously at rest, low-intensity exercise, and high-intensity exercise. Glycaemic control and lipid profile were assessed in the fasted state. Participants were assigned according to their exercise capacity being adequate or impaired (EXadequate O2peak <80% and EXimpaired O2peak ≥80% of predicted O2peak) to compare O2 extraction, CO, and LS at all stages. Thirty-eight participantals.gov/ct2/show/NCT03299790).

Effect of High-intensity Interval Training on Cardiac Function and Regulation of Glycemic Control in Diabetic Cardiomyopathy (https//clinicaltrials.gov/ct2/show/NCT03299790).

Epidemiological studies found a link between aircraft noise exposure and increased incidence of arterial hypertension and cardiovascular disease, but the underlying pathophysiological mechanisms are not fully understood. Clinical studies have shown that mental stress affects the systemic and renal haemodynamic, but no such study was performed with noise exposure as stress factor. We analysed systemic and renal effects of 25 min standardized aircraft noise in a sham controlled clinical study including 80 healthy men and 34 male patients with hypertension.

Systemic haemodynamic parameters were measured using electrocardiography and impedance cardiography. The renal haemodynamic was assessed using steady state input clearance with infusion of para-aminohippuric acid and inulin for glomerular filtration rate and renal plasma flow, respectively. In the systemic circulation of hypertensive patients, there was an increase in total peripheral resistance (TPR) (1420 ± 387 vs. 1640 ± 516 dyn·s·cm-5, P = 0.001) and ertensive patients are more susceptible for noise-induced changes of vascular resistance in the systemic circulation.

In hypertensive but not healthy men we observed a systemic vasoconstrictive response after aircraft noise exposure accompanied by a decrease in CI. No significant changes were observed in the renal circulation. Our results suggest that male hypertensive patients are more susceptible for noise-induced changes of vascular resistance in the systemic circulation.

Patients with heart failure and low income have a high mortality risk. We examined whether lower survival among low-income patients with heart failure could be explained by different use of β -blockers, renin-angiotensin system inhibitors (RASi), and implanted devices compared with high-income patients.

We linked Danish national registries to identify patients with new-onset heart failure between 2005 and 2016. A total of 18308 patients was included in the main analysis. We collected information on medical treatment and device therapy after discharge. We investigated the remaining income disparity if everybody had the same probability of treatment as the high-income patients. We used causal mediation analysis to examine to what extent treatment differences mediate the association between income and 1-year mortality in strata defined by sex and cohabitation status. If low-income patients had the same probability of initiating β-blockers and RASi treatment as high-income patients, low-income men who lived alone would increase initiation of treatment by 12.4% (CI 10.0% to 14.9%) and as a result reduce their absolute 1-year mortality by 1.0% (CI -1.4% to -0.5%). If low-income patients had the same probability of not having breaks in medical treatment and getting device therapy, as high-income patients, low-income patients would increase the probability of not having breaks in treatment between 1.8% and 5.8% and increase the probability of getting device therapy between 1.0% and 3.8%, across strata of sex and cohabitation status.

Lower rates of treatment initiation appear to mediate the poorer survival seen among patients with heart failure and low income, but only in males living alone.

Lower rates of treatment initiation appear to mediate the poorer survival seen among patients with heart failure and low income, but only in males living alone.

Hydroxychloroquine and chloroquine ([hydroxy]chloroquine) are drugs used to treat malaria and rheumatological disorders and were recently suggested as beneficial for prevention and treatment of patients with coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection. However, longitudinal studies to assess the electrocardiographic and cardiotoxic effects of these drugs are limited. In this study, we aimed to investigate the effect of these drugs on QTc-interval and incidence of sudden cardiac death (SCD).

We designed a longitudinal follow-up study of individuals within the prospective population-based Rotterdam Study. Eligible individuals had available data on medication and repeated ECG measurements. The study period was between 1 January 1991 and 1 January 2014. We studied on current and past use of [hydroxy]chloroquine as a time-varying exposure; high versus low daily dose of [hydroxy]chloroquine. QTc-interval duration, and the occurrence of SCD were the main outcomes. SCD was defined as an unexperoquine had an increased QTc-interval duration and the association was dose-dependent. [Hydroxy]chloroquine was associated with a significantly increased risk of SCD. As long as their activity against COVID-19 is controversial, cardiotoxicity is a strong argument against using these drugs to treat COVID-19 infections.

In this longitudinal study, persons who received [hydroxy]chloroquine had an increased QTc-interval duration and the association was dose-dependent. [Hydroxy]chloroquine was associated with a significantly increased risk of SCD. As long as their activity against COVID-19 is controversial, cardiotoxicity is a strong argument against using these drugs to treat COVID-19 infections.

The aim of this study is to analyse the prognostic implications of right ventricular (RV) dysfunction as detected by strain analysis in patients with severe tricuspid regurgitation (TR). The evaluation of RV systolic function in presence of severe TR is of paramount importance for operative risk stratification; however, it remains challenging, as conventional echocardiographic indexes usually lead to overestimation.

We enrolled 250 consecutive patients with severe TR referred to our centre. Baseline clinical and echocardiographic data and follow-up outcomes were collected. Patients were predominantly female, with multiple cardiovascular risk factors and comorbidities, history of heart failure, and atrial fibrillation. Most of them had presented with clinical signs of RV heart failure (RVHF) and advanced New York Heart Association class. The RV strain analysis [both RV free wall longitudinal strain (RVFWLS) and RV global longitudinal strain (RVGLS)] reclassified ∼42-56% of patients with normal RV systolic function according to conventional parameters in patients with impaired RV systolic function. RVFWLS ≤17% (absolute values, AUC 0.66, P = 0.002) predicted the presence of RVHF [odds ratio (OR) 0.93, P = 0.01]. At follow-up, patients with RVFWLS >14% (absolute values, AUC 0.70, P = 0.001, sensitivity 72%, specificity 54%) showed a better survival (P = 0.01).

Different ranges of RVFWLS have different implications in patients with severe TR, allowing to identify a preclinical and a clinical window, with correlations to RVHF and survival.

Different ranges of RVFWLS have different implications in patients with severe TR, allowing to identify a preclinical and a clinical window, with correlations to RVHF and survival.Oxygen is a pulmonary vasodilator. Although treatment of pulmonary arterial hypertension (PAH) is focused on pulmonary vasodilation, treatment guidelines do not recommend O2 therapy for patients unless they develop hypoxaemia. These guidelines point to a lack of evidence of benefit of O2 therapy from randomized controlled trials (RCTs) and to evidence of lack of benefit in a single RCT involving patients with Eisenmenger syndrome. These guidelines did not identify major limitations with the Eisenmenger study or consider other evidence of therapeutic benefit. Recent advances in mechanistic understanding of O2 effects on pulmonary vascular tone, along with substantial evidence of acute effects of O2 in PAH patients, challenge the view that benefits of O2 arise only through correction of hypoxaemia. Evidence presented in this review shows that O2 acts as a pulmonary vasodilator in patients who are normoxaemic; that this probably involves an alveolar mechanism in addition to a blood-borne (oxyhaemoglobin) mechanism; and that therapeutic benefit of O2 does not depend on arterial O2 levels. This suggests that O2 has potential therapeutic benefit for all patients with PAH. Clinical guidelines and practice related to O2 therapy need to be reassessed, and further research is needed.

Teleophthalmology may assist the healthcare sector in adapting to limitations imposed on clinical practice by a viral pandemic. A scoping review is performed in this study to assess the current applications of teleophthalmology for its suitability to diagnose, monitor or manage ophthalmological conditions with accuracy.

A search of PubMed was conducted for teleophthalmology-related articles published from 1 January 2018 to 4 May 2020. Only articles that focused on the use of teleophthalmology in terms of diagnosis and management, as well as its benefits and detriments, were included. The Mixed Methods Appraisal Tool (MMAT) was used to assess the quality of the included articles.

A total of 38 articles were assessed at the full-text level. There were 2 qualitative studies and 1 quantitative randomised controlled trial, while the majority were either quantitative descriptive studies (19, 50.0%) or quantitative non-randomised studies (16, 42.1%). Overall, 8 studies described reducing manpower requirements, 4 described reducing direct patient-doctor contact, 17 described storage of medical imaging and clinical data, and 9 described real-time teleconferencing. The MMAT analysis revealed limitations in appropriate sampling strategy in both quantitative non-randomised studies (9 of 16, 56.3%) and quantitative descriptive studies (9 of 19, 47.4%). Cost-effectiveness of teleophthalmology was not performed in any included study.

This current review of the various aspects of teleophthalmology describes how it may potentially assist the healthcare sector to cope with the limitations imposed by a viral pandemic through technology. Further research is required to evaluate the cost-effectiveness of the various strategies.

This current review of the various aspects of teleophthalmology describes how it may potentially assist the healthcare sector to cope with the limitations imposed by a viral pandemic through technology. Further research is required to evaluate the cost-effectiveness of the various strategies.

Coronavirus disease 2019 (COVID-19) cases are increasing rapidly worldwide. Similar to Middle East respiratory syndrome where cardiovascular diseases were present in nearly 30% of cases, the increased presence of cardiovascular comorbidities remains true for COVID-19 as well. The mechanism of this association remains unclear at this time. Therefore, we reviewed the available literature and tried to find the probable association between cardiovascular disease with disease severity and mortality in COVID-19 patients.

We searched Medline (via PubMed) and Cochrane Central Register of Controlled Trials for articles published until Sept 5, 2020. Nineteen articles were included involving 6,872 COVID-19 patients.

The random-effect meta-analysis showed that cardiovascular disease was significantly associated with severity and mortality for COVID-19 odds ratio (OR) 2.89, 95% confidence interval (CI) 1.98-4.21 for severity and OR 3.00, 95% CI 1.67-5.39 for mortality, respectively. Risk of COVID-19 severity was higher in patients having diabetes, hypertension, chronic obstructive pulmonary disease, malignancy, cerebrovascular disease and chronic kidney disease. Similarly, patients with diabetes, hypertension, chronic liver disease, cerebrovascular disease and chronic kidney disease were at higher risk of mortality.

Our findings showed that cardiovascular disease has a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid cardiovascular disease are urgently needed to understand the extent of these concerning comorbidities.

Our findings showed that cardiovascular disease has a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid cardiovascular disease are urgently needed to understand the extent of these concerning comorbidities.

Intubations in the emergency department (ED) are often performed immediately without the benefit of pre-selection or the ability to defer. Multicentre observational data provide a framework for understanding emergency airway management but regional practice variation may exist. We aim to describe the intubation indications, prevalence of difficult airway features, peri-intubation adverse events and intubator characteristics in the ED of the National University Hospital, Singapore.

We conducted a prospective observational study over a period of 31 months from 1 March 2016 to 28 September 2018. Information regarding each intubation attempt, such as indications for intubation, airway assessment, intubation techniques used, peri-intubation adverse events, and clinical outcomes, was collected and described.

There were 669 patients, with male predominance (67.3%, 450/669) and mean age of 60.9 years (standard deviation [SD] 18.1). Of these, 25.6% were obese or grossly obese and majority were intubated due to medical indications (84.8%, 567/669). Emergency physicians' initial impression of difficult airway correlated with a higher grade of glottis view on laryngoscopy. First-pass intubation success rate was 86.5%, with hypoxia (11.2%, 75/669) and hypotension (3.7%, 25/669) reported as the two most common adverse events. Majority was rapid sequence intubation (67.3%, 450/669) and the device used was most frequently a video laryngoscope (75.6%, 506/669). More than half of the intubations were performed by postgraduate clinicians in year 5 and above, clinical fellows or attending physicians.

In our centre, the majority of emergency intubations were performed for medical indications by senior doctors utilising rapid sequence intubation and video laryngoscopy with good ffirst-attempt success.

In our centre, the majority of emergency intubations were performed for medical indications by senior doctors utilising rapid sequence intubation and video laryngoscopy with good ffirst-attempt success.

Associations of variations in PLA2R1 and HLA-DQA1 genes with susceptibility to idiopathic membranous nephropathy (IMN) have been well documented. Association with spontaneous remission, however, is poorly defined in the Chinese Han population.

A Chinese cohort of 117 IMN patients and 138 healthy controls were recruited between July 2009 and November 2019. Case-control studies for single-nucleotide polymorphisms (SNPs) within HLA-DQA1 (rs2187668) and PLA2R1 (rs35771982, rs4664308, rs3749117, rs3749119) genes were performed. The contributions of these polymorphisms to predict susceptibility, titre of autoantibodies against the M-type phospholipase A2 receptor (anti-PLA2R1), glomerular PLA2R1 expression, and spontaneous remission were analysed.

We found that variations in PLA2R1 (SNPs rs35771982, rs4664308, rs3749117) were strongly associated with IMN susceptibility, while SNP (rs2187668) within HLA-DQA1 did not increase the risk of IMN. All SNPs in PLA2R1 and HLA-DQA1 were not statistically associated with anti-PLA2R1 titre, glomerular PLA2R1 expression and spontaneous remission after Bonferroni correction (

>0.0167). Clinical and pathological parameters such as lower levels of serum albumin, higher levels of anti-PLA2R1 and glomerular PLA2R1 expression were independent risk factors for non-spontaneous remission.

This study confirms that variations in PLA2R1 (SNPs rs35771982, rs4664308, rs3749117) are risk factors for IMN. We found excellent association of serum albumin level, anti-PLA2R1 titre and glomerular PLA2R1 positivity with non-spontaneous remission in IMN.

This study confirms that variations in PLA2R1 (SNPs rs35771982, rs4664308, rs3749117) are risk factors for IMN. We found excellent association of serum albumin level, anti-PLA2R1 titre and glomerular PLA2R1 positivity with non-spontaneous remission in IMN.

To evaluate the cost of inpatient rehabilitation for children with moderate to severe traumatic brain injury (TBI). Secondary aim was to identify factors associated with high inpatient rehabilitation cost.

Retrospective review of a tertiary hospital's trauma registry was performed from 2011-2017. All patients aged 16 years or younger who sustained TBI with Glasgow Coma Scale ≤13 were included. Data on patient demographics, mechanism and severity of injury, hospital duration and inpatient rehabilitation cost were collected. We performed a regression analysis to identify factors associated with high rehabilitation cost.

There were a total of 51 patients. The median duration of inpatient rehabilitation was 13.5 days (interquartile range [IQR] 4-35), amounting to a median cost of SGD8,361 (IQR 3,543-25,232). Daily ward costs contributed the most to total inpatient rehabilitation cost. Those with severe TBI had longer duration of inpatient rehabilitation that resulted in higher cost of inpatient rehabilitation. Presence of polytrauma, medical complications, post-traumatic amnesia and TBI post-non-accidental injury (NAI) were associated with higher cost of inpatient rehabilitation.

The cost of inpatient rehabilitation for paediatric patients post-TBI is significant in Singapore. Patients with TBI secondary to NAI had significantly higher cost of inpatient rehabilitation. Ways to reduce duration of hospitalisation post-TBI and early step-down care or outpatient rehabilitation should be explored to reduce cost.

The cost of inpatient rehabilitation for paediatric patients post-TBI is significant in Singapore. Patients with TBI secondary to NAI had significantly higher cost of inpatient rehabilitation. Ways to reduce duration of hospitalisation post-TBI and early step-down care or outpatient rehabilitation should be explored to reduce cost.

Diabetes increases the risk of ischaemic stroke especially among Asians. This study aims to investigate contemporaneous long-term cardiovascular outcomes of ischaemic stroke patients with diabetes in a multi-ethnic Asian cohort.

Consecutive patients with ischaemic stroke were recruited from the National University Hospital, Singapore. Data on age, gender, ethnicity, risk factors (including diabetes status and body mass index [BMI]), stroke severity and mechanisms were collected. These patients were followed up until the day of the first cardiovascular event or July 2016, whichever was earlier. The primary endpoint was the time from enrolment to the first occurrence of a composite of cerebrovascular and coronary artery events.

Between July 2011 and December 2013, 720 patients (mean age 60.6 years, 71% men, 43% with diabetes, median National Institute Health Stroke Severity scale 2) were enrolled and followed up. A total of 175 cardiovascular events occurred during a median follow-up of 3.25 years (6.90 events per 1,000 person-month), comprising 133 cerebrovascular and 42 coronary artery events. The adjusted hazard ratio of diabetes was 1.50 (95% CI 1.08-2.10). In a multivariable Cox proportional hazards model, Malay and Indian ethnicities, BMI <23kg/m2 and a prior diagnosis of diabetes were identified as independent predictors of recurrent cardiovascular events.

Our study provides quantitative data on the event rates of ischaemic stroke patients with diabetes. These findings provide insights on stroke predictors in a multi-ethnic Asian population, which may have implications in the design of future interventional studies.

Our study provides quantitative data on the event rates of ischaemic stroke patients with diabetes. These findings provide insights on stroke predictors in a multi-ethnic Asian population, which may have implications in the design of future interventional studies.

Uterine rupture is uncommon but has catastrophic implications on the pregnancy. A scarred uterus and abnormal placentation are known contributory factors. The aim of our study was to review the contributing factors, clinical presentation, complications and management of uterine rupture in our population in light of the changing nature of modern obstetric practices.

A retrospective observational study was conducted at KK Women's and Children's Hospital by studying proven cases of uterine rupture in the period between January 2003 and December 2014. These cases were analysed according to their past history, clinical presentation, complications, management and outcome.

A total of 48 cases of proven uterine rupture were identified. The incidence of uterine rupture was 1 in 3,062 deliveries. The ratio of scarred uterus rupture to unscarred uterus rupture was approximately 31. The most common factor was previous lower segment caesarean section for the scarred group, followed by a history of laparoscopic myomectomy. Abdominal pain was the common clinical presentation in the antenatal period, while abnormal cardiotocography findings were the most common presentation in intrapartum rupture.

There is a notable shift in the trend of uterine rupture cases given the increasing use of laparoscopic myomectomy and elective caesarean sections. While ruptures from these cases were few, their presentation in the antenatal period calls for diligent monitoring with informed patient involvement in their pregnancy care.

There is a notable shift in the trend of uterine rupture cases given the increasing use of laparoscopic myomectomy and elective caesarean sections. While ruptures from these cases were few, their presentation in the antenatal period calls for diligent monitoring with informed patient involvement in their pregnancy care.Developing ultra-stretchable, universally sticky, and highly conductive nanocomposite hydrogels without doping agents and nanoparticle-aggregation is still a challenge. Herein, doping-free and nanoparticle-aggregation-inhibited hydrogels composed of Fe3+, dopamine (DA), pyrrole (Py) and polyacrylic acid (PAA) were prepared. Polypyrrole-polydopamine (PPy-PDA)/PAA hydrogels were quickly formed due to the abundant ionic bonds and physical cross-linking under the addition of Fe3+. Moreover, the H+ ions of the carboxylic acid groups on the PAA polymer chain helped to improve the conductivity of the hydrogels. Surprisingly, the multi-functional hydrogels received a high stretchability of 1900%, a tissue-like elastic modulus of 22 kPa, an adhesive strength of 2125.9 J m-2, and a high conductivity of 0.39 S m-1. Besides, the PPy-PDA/PAA hydrogels showed good antioxidant activity, biocompatibility and tissue repairing behavior. In short, the prepared multi-functional hydrogels have potential to address the human clinical problem of tissue repair and regeneration.Inverse bicontinuous cubic phase nanoparticles (cubosomes) have attracted significant attention in recent years, owing to their potential use as delivery vehicles for chemically fragile or poorly soluble drugs and nutraceuticals. Herein we have investigated the use of lipid nanoparticles as a delivery vehicle for curcumin, a compound with demonstrated anti-cancer properties. Curcumin is encapsulated within cubosomes comprised of several different lipid formulations, as well as phospholipid-based liposomes. The entrapment efficiency of curcumin within cubosomes was observed to vary depending on both the nanoparticle architecture and the curcumin concentration. Fluorescence spectroscopy analysis revealed that penetration of curcumin into the hydrophobic region of the bilayer was dependent on lipid composition. Curcumin was typically associated with the polar headgroup region at low concentrations, but transferred to the lipid bilayer region at higher concentrations, particularly in phytantriol cubosomes. Each nanoparticle formulation was characterized using small angle X-ray scattering and dynamic light scattering to assess the structural stability subsequent to curcumin encapsulation.