Non-vitamin K oral anticoagulants versus warfarin for the treatment of left ventricular thrombus.

INTRODUCTION: Left ventricular thrombus (LVT) is associated with significant morbidity and mortality. Conventional treatment comprises warfarin-mediated anticoagulation; it is unclear whether non-vitamin K oral anticoagulants (NOACs) exhibit comparable efficacy and safety. Limited data are available for Asian patients. This study compared NOACs with warfarin in terms of clinical efficacy and safety for managing LVT. METHODS: Clinical and echocardiographic records were retrieved for all adult patients with echocardiography-confirmed LVT at a major regional centre in Hong Kong from January 2011 to January 2020. Discontinuation of anticoagulation by 1 year was recorded. Outcomes were compared between patients receiving NOACs and those receiving warfarin. Primary outcomes were cumulative mortality and net adverse clinical events (NACEs). Secondary outcomes were complete LVT resolution and percentage reduction in LVT size at 3 months. RESULTS: Forty-three patients were included; 28 received warfarin and 15 received NOACs, with follow-up periods (mean ± standard deviation) of 20 ± 12 months and 22 ± 9 months, respectively (P=0.522). Use of NOACs was associated with significantly lower NACE risk (hazard ratio [HR]=0.111, 95% confidence interval [CI]=0.012-0.994; P=0.049) and a tendency towards lower cumulative mortality (HR=0.184, 95% CI=0.032-1.059; P=0.058). There were no significant differences in secondary outcomes. Considering LVT resolution, discontinuation of anticoagulation by 1 year was not significantly associated with different outcomes. CONCLUSION: Non-vitamin K oral anticoagulants may be an efficacious and safe alternative to warfarin for LVT management. Future studies should explore the safety and efficacy of anticoagulation discontinuation by 1 year as an overall strategy.

Renal outcomes in Asian patients receiving oral anticoagulants for non-valvular atrial fibrillation.

INTRODUCTION: Patients with non-valvular atrial fibrillation (NVAF) may be prescribed warfarin or a non-vitamin K oral anticoagulant (NOAC). There is increasing evidence that NOACs are superior to warfarin in terms of renal function preservation. This study aimed to compare renal outcomes in Chinese patients with NVAF between patients receiving NOACs and patients receiving warfarin. METHODS: In total, 600 Chinese patients with NVAF receiving oral anticoagulant therapy were retrospectively identified from an administrative database. The renal outcomes (≥30% decline in estimated glomerular filtration rate [eGFR], doubling of serum creatinine, and kidney failure) were compared among four propensity-weighted treatment cohorts (warfarin, n=200; rivaroxaban, n=200; dabigatran, n=100; and apixaban, n=100). RESULTS: The mean follow-up period across all groups was 1000 ± 436 days. Compared with warfarin, the three NOACs (pooled for consideration as a single unit) had significantly lower risks of ≥30% decline in eGFR (hazard ratio [HR]=0.339; 95% confidence interval [CI]=0.276-0.417) and doubling of serum creatinine (HR=0.550; 95% CI=0.387-0.782). Dabigatran and rivaroxaban users both had lower risks of ≥30% decline in eGFR (both P<0.001) and doubling of serum creatinine (both P<0.05). Apixaban was only significantly associated with a lower risk of ≥30% decline in eGFR (P<0.001). CONCLUSIONS: Compared with warfarin, NOACs may be associated with a significantly lower risk of decline in renal function among Chinese patients with NVAF.

Echocardiography update for primary care physicians: a review.

Echocardiography is a key evaluation tool for the diagnosis, prognosis, and guidance of interventional management of numerous cardiovascular conditions, including ischaemia, heart failure, and structural heart diseases. Recent technological advancements have also seen the exploration of artificial intelligence, intracardiac vortex imaging, and three-dimensional printing in echocardiography. With cardiovascular diseases increasing in prevalence worldwide, it is important for clinicians including general practitioners to have updated knowledge of appropriate use of echocardiography. As such, this article reviews the current literature and summarises the latest developments and the general clinical usage of echocardiography.

Acute hantavirus infection presenting as haemolytic-uraemic syndrome (HUS): the importance of early clinical diagnosis.

The European prototype of hantavirus, Puumala virus (PUUV), isolated from a common wild rodent, the bank vole (Myodes glareolus), causes nephropathia epidemica (NE). NE can perfectly mimic haemolytic-uraemic syndrome (HUS), progressing from an aspecific flu-like syndrome to acute kidney injury with thrombocytopaenia, and presenting with some signs of haemolytic anaemia and/or coagulopathy. Moreover, both NE and HUS can occur in local outbreaks. We report an isolated case of NE, initially referred for plasmapheresis for suspected HUS, although signs of overt haemolysis were lacking. Early suspicion of hantavirus infection, later confirmed by serology and reverse transcription polymerase chain reaction (RT-PCR), prevented subsequent excessive treatment modalities.

The influence of ultra-pasteurization by indirect heating versus direct steam injection on skim and 2% fat milks.

Fluid milk is traditionally pasteurized by high temperature, short time (HTST) pasteurization, which requires heating to at least 72°C for 15 s. Ultra-pasteurization (UP) extends milk shelf life and is defined as heating to at least 138°C for 2 s. The UP process can be done by indirect heating (IND) or by direct steam injection (DSI). The influence of these 2 UP methods on milk flavor has not been widely investigated. The objective of this study was to compare the effect of HTST, IND-UP, and DSI-UP on sensory perception of fluid milk. Raw skim and standardized 2% milks were pasteurized at 140°C for 2.3 s by IND or DSI or by HTST (78°C, 15 s) and homogenized at 20.7 MPa. The processed milks were stored in light-shielded opaque high-density polyethylene containers at 4°C and examined by descriptive analysis and microbial analysis on d 3, 7, and 14. Furosine and serum protein denaturation analyses were performed on d 0 and 14 as an indicator of heat treatment. Last, consumer acceptance testing was conducted at d 10, with adults (n = 250) and children (ages 8 to13 y, n = 100) who were self-reported consumers of skim or 2% milk; consumers only received samples for either skim or 2% milk. The entire experiment was repeated in triplicate. Milks treated by HTST had lower cooked flavor than either UP milk. Milks heated by DSI-UP were characterized by sulfur or eggy and cooked flavors, whereas IND-UP milks had higher sweet aromatic and sweet taste compared with DSI-UP milk. Aromatic flavor intensities of all milks decreased across 14 d of storage. Furosine concentrations and serum protein denaturation were highest for the IND treatments, followed by DSI and HTST. Furosine content in both skim and 2% milk increased with time, but the increase was faster in IND-UP skim milk. Adult and child consumers preferred HTST milk over either UP milk, regardless of fat content. Ultra-pasteurization by IND or DSI did not affect consumer acceptance at 10 d postprocessing, but traditional HTST milks were preferred by consumers of all ages.

Short communication: The effect of raw milk cooling on sensory perception and shelf life of high-temperature, short-time (HTST)-pasteurized skim milk.

The cooling rate of raw milk may influence sensory properties and pasteurized shelf life. Under the Pasteurized Milk Ordinance for grade A milk, raw milk may be cooled instantaneously by on-farm heat exchangers but is also acceptable if "cooled to 10°C or less within four (4) hours of the commencement of the first milking." The objective of this study was to determine the effect of raw milk cooling on consumer perception and shelf life. Raw milk (18-21°C) was obtained and transported within 1h of milking to North Carolina State University (Raleigh). The batch of raw milk was split in 2 portions, and a plate heat exchanger was used to quickly cool one portion to <6°C within 1min. The second portion was stored in a jacketed bulk tank and slowly cooled over 4h to <10°C. Milk from 3 consecutive milkings was collected every 12h, with subsequent milkings added to the previous collections. The bulk milk was kept below 10°C while adding milk for the slow cool milk treatment. After 72h, each whole milk was separated; the skim milk was pasteurized at 73 or 78°C for 20 s, homogenized, and held at 4°C. Difference tests (n=75) and consumer acceptance tests (n=100) were conducted to determine if consumers could detect differences among milks. Descriptive analysis and microbial testing for aerobic, psychrotrophic, and psychrotolerant spore counts were conducted through shelf life. The entire experiment was repeated in triplicate. Raw milks averaged 3.3 logcfu/mL by aerobic plate count, <25cfu/mL coliforms, somatic cell count of 300,000 cells/mL, and 3.15±0.07% protein. Psychrotolerant spores were not found in the raw milk. Consumers could not detect differences between cooling treatments of the same pasteurization temperature or between different temperatures of the same cooling treatment. Milks reached sensory failure 49±4d on average after processing, and aerobic counts were between 5 to 7 logcfu/mL. Cooling treatment had no effect on shelf life. These results suggest that pasteurized milk quality is due to a combination of many factors. Raw milk cooling rate is not the most important factor affecting milk quality when raw milk quality is excellent.

Membrane biophysics define neuron and astrocyte progenitors in the neural lineage.

Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self-renewing stem cells and more committed progenitors that differentiate into neurons, astrocytes, and oligodendrocytes. Accurately identifying and characterizing the different progenitor cells in this lineage has continued to be a challenge for the field. We found previously that populations of NSPCs with more neurogenic progenitors (NPs) can be distinguished from those with more astrogenic progenitors (APs) by their inherent biophysical properties, specifically the electrophysiological property of whole cell membrane capacitance, which we characterized with dielectrophoresis (DEP). Here, we hypothesize that inherent electrophysiological properties are sufficient to define NPs and APs and test this by determining whether isolation of cells solely by these properties specifically separates NPs and APs. We found NPs and APs are enriched in distinct fractions after separation by electrophysiological properties using DEP. A single round of DEP isolation provided greater NP enrichment than sorting with PSA-NCAM, which is considered an NP marker. Additionally, cell surface N-linked glycosylation was found to significantly affect cell fate-specific electrophysiological properties, providing a molecular basis for the cell membrane characteristics. Inherent plasma membrane biophysical properties are thus sufficient to define progenitor cells of differing fate potential in the neural lineage, can be used to specifically isolate these cells, and are linked to patterns of glycosylation on the cell surface.

Vitamins B-12 and C Supplementation Improves Arterial Reactivity and Structure in Passive Smokers: Implication in Prevention of Smoking-Related Atherosclerosis.

BACKGROUND: Atherosclerosis is an important medical problem of modern society. High environmental tobacco smoke in casino is associated with an accelerated atherogenic process. We have previously shown vitamin B12 and C supplementation improves vascular reactivity and may be beneficial in vascular protection. OBJECTIVE: To evaluate the impact of vitamin supplementation on atherosclerosis (brachial artery reactivity FMD and carotid intima-media thickness IMT) in subjects exposed to high environmental tobacco smoke. DESIGN: Double-blind 2x2 factorial design fashion. SETTING: Computer randomization in 4 treatment groups: placebo (n=24), vitamin B12 (n=21), vitamin C (n=23) and vitamin B12+C (n=23) groups. PARTICIPANTS: 91 passive-smoking casino employees (19.2% male, mean age 45.0±8.2 years). INTERVENTION: Subjects were randomized to receive vitamin B12 (500µg daily), vitamin C (200mg daily), vitamin B12+C or image-matched placebo capsules for 1 year. MEASUREMENT: Brachial FMD and carotid IMT (surrogate atherosclerotic markers) were measured by ultrasound at baseline and on completion at 12 months. METHODS: 91 passive smoking casino employees (19.2% male, mean age 45.0±8.2 years) were randomized to receive vitamin B12 (500µg daily), vitamin C (200mg daily), vitamin B12+C or image-matched placebo capsules in double-blind 2 x 2 factorial design fashion for 1 year. Brachial FMD and carotid IMT (surrogate atherosclerotic markers) were measured by ultrasound at baseline and 12 months. RESULTS: Of the 78 (85.7%) passive-smoking employees completed the study, 11.5% had hypertension, 5.1% diabetes mellitus and 15.4% hypercholesterolemia. There were no significant changes in their blood pressures, lipid profiles, glucose and body mass index after supplementation for 1 year, but mild decrease in DBP (p<0.001) and blood creatinine (p<0.01) after combined vitamin B12 and C, and significant increase in blood B12 after vitamin B12 (p<0.01) and vitamin B12+C supplementations (p<0.001). Brachial FMD and cartotid IMT improved after the 3 vitamin supplementations (p<0.001), but not after placebo, being more significant after combined vitamin supplementations (p<0.0001). No adverse effects were reported. CONCLUSION: Vitamin B12 or C supplementation in passive smokers improved vascular reactivity and structures at 1 year, with implication in long term atherosclerosis prevention.

Counting single molecules in sub-nanolitre droplets.

We demonstrate single biomolecule detection and quantification within sub-nanolitre droplets through application of Cylindrical Illumination Confocal Spectroscopy (CICS) and droplet confinement within a retractable microfluidic constriction.

Cardiac Manifestations of Sarcopenia.

OBJECTIVES: Screening questions for sarcopenia used in the community (SARC-F) may be regarded as indicators of exercise tolerance. DESIGN: Observational study. SETTING: We tested the hypothesis that community-living older people who are screened positive for sarcopenia using the SARC-F tool but without a history of heart failure (HF) have a higher prevalence of cardiac abnormalities compared with those who are SARC-F negative. PARTICIPANTS: Participants were recruited from a territory-wide primary care needs assessment for older people based in community centres, and from non-acute hospitals in the same region as the study centre. MEASUREMENTS: Participants with a total score of >=4 and who did not have any history of HF were invited to attend for further cardiac assessment. Grip strength, walking speed, and the 6-minute walk test and echocardiography were carried out. Patients with frailty and at least Grade II diastolic dysfunction were considered to have heart failure with preserved ejection fraction (HFpEF) if they also had concomitant elevated N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) of at least 300 pg/ml. RESULTS: Diastolic dysfunction (DD) was significantly associated with SARC-F score >=4 and higher circulating NT-proBNP levels. ROC curves evaluating the predictive values of SARC-F, HGS and gait speed for DD showed that a combination of SARC-F and HGS or gait speed provided significant incremental value in predicting DD. CONCLUSIONS: Community living older people with sarcopenia detected using a simple questionnaire have a higher prevalence of DD accompanied by elevated NT proBNP. Addition of hand grip strength or walking speed improve the magnitude of the association. SARC-F may be used as a tool to detect early cardiac dysfunction in the community.

Utility of the FRAIL Questionnaire in Detecting Heart Failure with Preserved Ejection Fraction.

OBJECTIVE: To test the utility of the FRAIL questionnaire as a screening tool for heart failure. DESIGN: Cross sectional study. SETTING: Chinese older people in Hong Kong. PARTICIPANTS: Participants aged 60 years and over were recruited from a territory-wide primary care needs assessment for older people based in community centers as well as two nonacute hospitals. MEASUREMENTS: Questionnaire administered included the five-item FRAIL scale, and information regarding sociodemographic data, smoking and alcohol use, history of cardiovascular disease and diabetes, and heart failure symptoms. Handgrip strength, walking speed and 6 minute walk distance were recorded. Cardiac assessment included electrocardiogram, echocardiography, and blood assay for N-terminal prohormone of B-type natriuretic peptide (NT-proBNP). RESULTS: The prevalence of diastolic dysfunction was high, being 52% in the robust group, increasing to 65% in the pre-frail and 85% in the frail group. This finding is accompanied by a corresponding increase in NT-proBNP from 64.18 pg/ml in the robust group, to 118.57 pg/ml in the pre-frail and 167.98 pg/ml in the frail group. Three of the five components of the FRAIL scale, fatigue, resistance and ambulation, were associated with increased odds ratios of diastolic dysfunction among those aged 75 years and older, while resistance alone was associated with increased odds ratio among those less than 75 years old. CONCLUSION: Frailty is associated with heart failure with preserved ejection fraction (HFpEF), and frailty screening may be used to detect undiagnosed HFpEF. The findings support the proposal that HFpEF be considered a geriatric syndrome.

Cell-sized lipid vesicles for cell-cell synaptic therapies.

Cell-sized lipid vesicles (CLVs) have shown great promise for therapeutic and artificial cell applications, but their fragility and short shelf life has hindered widespread adoption and commercial viability. We present a method to circumvent the storage limitations of CLVs such as giant unilamellar vesicles (GUVs) and single-compartment multisomes (SCMs) by storing them in a double emulsion precursor form. The double emulsions can be stored for at least 8 months and readily converted into either GUVs or SCMs at any time. In this study, we investigate the interfacial parameters responsible for this morphological change, and we also demonstrate the therapeutic potential of CLVs by utilizing them to present a transmembrane protein, neuroligin-2, to pancreatic ß-cells, forming cell-cell synapses that stimulate insulin secretion and cellular growth.

[Health care usage by minimum income citizens in Amsterdam; a cross-sectional study into claims within the Dutch basic health insurance scheme]. / Het zorggebruik van minima in Amsterdam.

OBJECTIVE: Gaining more insight into any differences in care expenses between minimum and higher income groups. DESIGN: Cross-sectional study among 6,709 citizens of Amsterdam aged 19 years and over. METHOD: Data on declared health care expenses from 2012 were linked to personal income and to public health survey data. Through weighted logistic regression analysis, differences in expenses for primary care, hospital care, mental health care and other care were compared for minimum and higher income groups, controlling for demographic characteristics, educational level and health status. RESULTS: Minimum income groups claimed more often for mental health care costs (11%) than higher income groups (7%). However, after controlling for demographic characteristics, educational level and health status this difference was not significant. Further, minimum income groups claimed fewer expenses for hospital care, but this difference was not significant. The number of claims for other care did not differ. The size of the expenses differed between income groups. Expenses for primary care among minimum income groups were lower versus those for higher earners. Expenses for hospital care, mental health care and other care were higher, but not to a statistically significant level. CONCLUSION: Minimum income groups claim lower costs for primary care. On the other hand, the number of claims for mental health care, hospital care and other care is equal or higher than that of higher income citizens, as is the size of the claimed expenses.

Effectiveness in controlling haemorrhage after dental scaling in people with haemophilia by using tranexamic acid mouthwash.

AIMS: To compare the effectiveness of tranexamic acid mouthwash (TAMW) in controlling gingival haemorrhage after dental scaling with that of using factor replacement therapy (FRT) prior to dental scaling in people with haemophilia. DESIGN: Double-blind cross-over randomised control trial. SETTING: Dedicated hospital dental practice for patients with inherited bleeding disorders. METHOD: Sixteen patients with haemophilia who required dental scaling participated in this pilot study. The experimental treatment regime (ETR) involved transfusing each patient with saline before scaling both quadrants on one side of the mouth followed by oral rinsing with TAMW four times daily for up to eight days. The control regime (CR) involved giving each patient FRT before scaling the opposite side of the mouth followed by use of a placebo TAMW. Each patient underwent both treatments in a random-ised sequence. Both the operator and the patients were unaware of which were the ETR and CR episodes. On both occasions the patient kept a log book of the rinsing regime and any post-operative bleeding. Additionally, a structured post-treatment telephone interview was conducted to assess the effectiveness and the patient acceptability of the ETR. RESULTS: Thirteen patients completed the study. No statistically significant difference was found in gingival bleeding and mouthwashing frequencies between the ETR and the CR (p > 0.05). Five patients reported no gingival bleeding with either the ETR or the CR. No patient, using either regime, required extra FRT due to gingival haemorrhage. All subjects found the ETR acceptable and easy and reported feeling safe in using TAMW alone to control gingival bleeding after dental scaling. CONCLUSION: TAMW use after dental scaling was as effective as using FRT beforehand in controlling gingival haemorrhage for people with haemophilia.

A fenestrated aortic valve contributing to iatrogenic aortic insufficiency post mitral valve replacement.

A case of an unusual local complication of cardiac valvular surgery is presented. Distortion of the geometry of the aortic valve base by a prosthetic mitral valve sewing ring allowed aortic insufficiency through the aortic valve's central orifice, as well as through an aortic valve cusp fenestration. During the 6 years after valve surgery, this patient developed chronic left heart failure contributed to by the aortic insufficiency and eventually, at age 65, required cardiac transplantation. Surgeons and pathologists should be aware of this unusual local complication of cardiac valve surgery, as it may have serious consequences.

A brain-tumor model utilizing stereotactic implantation of a permanent cannula.

A tumor model involving stereotactically implanted culture-reared tumor cells is presented. Stainless steel cannulas were stereotactically and permanently implanted into the caudate nucleus of 30 rats. The animals were separated into two groups. In Group I, 15 animals received a 10-microliters injection containing 10(6) C6 glioblastoma cells (five rats), 10(6) Walker 256 breast carcinoma cells (five rats), or cell medium (five rats). The coordinates were A(+1.5), L(+3.0), and DV(-5.0). In Group II, the coordinates were changed to A(+1.0), L(+3.0), and DV(-5.0) and the same number of rats received a 1-microliter injection containing 10(5) cells of each tumor in an attempt to produce more focal tumors. Two weeks after implantation, brain sections were stained with cresyl violet and a subset was stained for glial fibrillary acid protein (GFAP). A computerized morphometric analysis system was used to quantify tumor size. In Group I, the mean C6 tumor areas (+/- standard error of the mean) at specific coordinates were (in sq mm): A(+4.7) 0.4 +/- 0.2; A(+3.7) 3.5 +/- 1.1; A(+2.7) 5.7 +/- 1.7; A(+1.7) 9.5 +/- 2.3; A(+0.7) 7.5 +/- 3.2; A(-0.3) 3.7 +/- 2.9; and A(-1.3) 0.3 +/- 0.3. A nearly identical tumor mass and extension into the brain was produced in rats injected with Walker 256 cells. Similar C6 tumor areas were indicated in adjacent sections stained with cresyl violet and GFAP. Tumor was found in the caudate nucleus in all 10 rats, but not in the nucleus accumbens, fornix, or hippocampus. In Group II animals, tumor magnitude and extension into the brain were greatly reduced. The 10(6) cells in the 10-microliters volume was the most reliable tumor load for obtaining uniform tumors in different animals. The similarity of tumor distribution across different animals was indicated by the low variance of tumor area at specific anteroposterior coordinates. Reproducible and well-circumscribed caudate nucleus tumors were produced using this stereotactic procedure.

The use of environmental risk assessment methodologies for an indoor air quality investigation.

The authors of this paper chose several target compounds that have been found in average US homes, applied the current United States Environmental Protection Agency (USEPA) Superfund risk assessment methodologies to indoor air quality, and produced risk numbers for hazard quotients and predicted increases in incidence of cancer which would be unacceptable at US hazardous waste sites. The calculations were made for the average child and adult with USEPA default exposure values. Calculations were also made for a worst case scenario using maximum concentrations and exposure estimates defined by the USEPA as describing the reasonable exposure (RME). Significant cancer risks and non-cancer hazard quotients were predicted.