To confirm whether a relationship exists between male sex and coronavirus disease 2019 (COVID-19) mortality and whether this relationship is age dependent.
We queried the COVID-19 Research Network, a ...multinational database using the TriNetX network, to identify patients with confirmed COVID-19 infection. The main end point of the study was all-cause mortality.
A total of 14,712 patients were included, of whom 6387 (43%) were men. Men were older (mean age, 55.0±17.7 years vs 51.1±17.9 years; P<.001) and had a higher prevalence of hypertension, diabetes, coronary disease, obstructive pulmonary disease, nicotine dependence, and heart failure but a lower prevalence of obesity. Before propensity score matching (PSM), all-cause mortality rate was 8.8% in men and 4.3% in women (odds ratio, 2.15; 95% CI, 1.87 to 2.46; P<.001) at a median follow-up duration of 34 and 32 days, respectively. In the Kaplan-Meier survival analysis, the cumulative probability of survival was significantly lower in men than in women (73% vs 86%; log-rank, P<.001). After PSM, all-cause mortality remained significantly higher in men than in women (8.13% vs 4.60%; odds ratio, 1.81; 95% CI, 1.55 to 2.11; P<.001). In the Kaplan-Meier survival analysis, the cumulative probability of survival remained significantly lower in men than in women (74% vs 86%; log-rank, P<.001). The cumulative probability of survival remained significantly lower in propensity score-matched men than in women after excluding patients younger than 50 years and those who were taking angiotensin-converting enzyme inhibitor or angiotensin receptor blocker medications on admission.
Among patients with COVID-19 infection, men had a significantly higher mortality than did women, and this difference was not completely explained by the higher prevalence of comorbidities in men.
Achieving a spatial resolution that is not limited by the diffraction of light, recent developments of super-resolution fluorescence microscopy techniques allow the observation of many biological ...structures not resolvable in conventional fluorescence microscopy. New advances in these techniques now give them the ability to image three-dimensional (3D) structures, measure interactions by multicolor colocalization, and record dynamic processes in living cells at the nanometer scale. It is anticipated that super-resolution fluorescence microscopy will become a widely used tool for cell and tissue imaging to provide previously unobserved details of biological structures and processes.
Recent advances in far-field fluorescence microscopy have led to substantial improvements in image resolution, achieving a near-molecular resolution of 20 to 30 nanometers in the two lateral ...dimensions. Three-dimensional (3D) nanoscale-resolution imaging, however, remains a challenge. We demonstrated 3D stochastic optical reconstruction microscopy (STORM) by using optical astigmatism to determine both axial and lateral positions of individual fluorophores with nanometer accuracy. Iterative, stochastic activation of photoswitchable probes enables high-precision 3D localization of each probe, and thus the construction of a 3D image, without scanning the sample. Using this approach, we achieved an image resolution of 20 to 30 nanometers in the lateral dimensions and 50 to 60 nanometers in the axial dimension. This development allowed us to resolve the 3D morphology of nanoscopic cellular structures.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Polyclonal anti-immunoglobulin G (anti-IgG) secondary antibodies are essential tools for many molecular biology techniques and diagnostic tests. Their animal-based production is, however, a major ...ethical problem. Here, we introduce a sustainable alternative, namely nanobodies against all mouse IgG subclasses and rabbit IgG. They can be produced at large scale in
and could thus make secondary antibody production in animals obsolete. Their recombinant nature allows fusion with affinity tags or reporter enzymes as well as efficient maleimide chemistry for fluorophore coupling. We demonstrate their superior performance in Western blotting, in both peroxidase- and fluorophore-linked form. Their site-specific labeling with multiple fluorophores creates bright imaging reagents for confocal and superresolution microscopy with much smaller label displacement than traditional secondary antibodies. They also enable simpler and faster immunostaining protocols, and allow multitarget localization with primary IgGs from the same species and of the same class.
We have developed a high-resolution fluorescence microscopy method based on high-accuracy localization of photoswitchable fluorophores. In each imaging cycle, only a fraction of the fluorophores were ...turned on, allowing their positions to be determined with nanometer accuracy. The fluorophore positions obtained from a series of imaging cycles were used to reconstruct the overall image. We demonstrated an imaging resolution of 20 nm. This technique can, in principle, reach molecular-scale resolution.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
One approach to super-resolution fluorescence imaging uses sequential activation and localization of individual fluorophores to achieve high spatial resolution. Essential to this technique is the ...choice of fluorescent probes; the properties of the probes, including photons per switching event, on-off duty cycle, photostability and number of switching cycles, largely dictate the quality of super-resolution images. Although many probes have been reported, a systematic characterization of the properties of these probes and their impact on super-resolution image quality has been described in only a few cases. Here we quantitatively characterized the switching properties of 26 organic dyes and directly related these properties to the quality of super-resolution images. This analysis provides guidelines for characterization of super-resolution probes and a resource for selecting probes based on performance. Our evaluation identified several photoswitchable dyes with good to excellent performance in four independent spectral ranges, with which we demonstrated low-cross-talk, four-color super-resolution imaging.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Concerns have been recently raised about young patients with COVID-19 presenting with large ischemic strokes.1 Data on stroke in COVID-19 patients remain limited to a few case reports.1 In this ...focused analysis, we investigated the incidence and outcomes of acute ischemic stroke in young adults using a multinational database. TriNetX is a global federated health research network providing access to statistics on electronic medical records (diagnoses, procedures, medications, laboratory values, genomic information) from patients in predominately large healthcare organizations. To our knowledge, this is the first study to report the incidence and outcomes of acute ischemic stroke in young adults with COVID-19 infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
The opioid crisis has disproportionally affected Appalachia. One of the potentially lethal and costly complications associated with IV drug use is infective endocarditis (IE). The goal of ...this study was to assess the trend and costs of substance abuse associated IE admissions in Southern West Virginia.
Methods
This is a retrospective analysis of cost, incidence, and geographic patterns of all patients admitted over the last decade with concomitant drug abuse (cocaine, amphetamine, sedative, and other/mixed drug abuse) and IE in the largest tertiary care center for Southern West Virginia. A time series model was used to investigate the effect of drug use on the incidence of IE.
Results
A total of 462 patients were hospitalized with IE and concomitant illicit drug use. IE cases increased from 26 admissions in 2008 to 66 in 2015. Patterns of increases in mixed drug use (DRG most often associated with IV drug use in our center) mirrored increases in IE (P = 0.001). From 2008 to 2015, the total hospital charges were $17 306 464 on 462 cases of illicit drug associated IE. Only a fraction of the billed fees (22%) was collected ($3 829 701).
Conclusions
The number of patients hospitalized with IE has dramatically increased over the last decade in a pattern that mirrors the increase in mixed drug use. The majority of payers were from underfunded state programs or private pay and thus, only 22% of the hospital charges were paid, leaving a hospital deficit of over $13 476 763 during the study period.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The field of transcatheter aortic valve replacement (TAVR) has matured significantly with the outcome and durability data now supporting use in lower‐risk patients. We present a preventable ...complication from early in our experience (5 years ago) that illustrates the importance of heart team communication and cautious multidiscipline cross‐pollination during the formative years of a program. An 87‐year old female developed confusion, slurred speech and left upper extremity weakness 1 day following TAVR with inconclusive findings on carotid artery duplex and transthoracic echocardiography. Subsequent CT‐scan disclosed a linear, ring‐like, structure in the ascending aorta. The foreign body (FB) was radiolucent and successfully snared via tactile sensation and anatomic landmarks informed by the CT. The extricated FB was the valvuloplasty balloon guard (BG) that was inadvertently introduced into the patient via ascending aortic large sheath access. The failure mode was traced back to the first time use of a new balloon system and unrecognized BG by the surgical physician and technician components of the Heart Team who took the lead role in device insertion due to the open chest access. Subsequently, the heart team made changes to mitigate similar future complications by sharing multidiscipline responsibility for all procedural steps and ensuring the use of all new adjuvant devices are preceded by a procedural pause and team consensus regarding device preparation and use. Additionally, the manufacturer addition of a radiopaque marker or flair on the valvuloplasty BG may be warranted.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Carotid baroreflex activation lowers blood pressure and might have potential application for the treatment of resistant hypertension. We did a proof-of-principle trial with a novel endovascular ...baroreceptor amplification device, MobiusHD (Vascular Dynamics, Mountain View, CA, USA), in patients with resistant hypertension.
CALM-FIM_EUR was a prospective, first-in-human, open-label study done at six European centres. Eligible patients were adults with resistant hypertension (office systolic blood pressure ≥160 mm Hg despite taking at least three antihypertensive agents, including a diuretic). MobiusHD devices were implanted unilaterally in the internal carotid artery. The primary endpoint was the incidence of serious adverse events at 6 months. Secondary endpoints included changes in office and 24 h ambulatory blood pressure. This trial is registered with ClinicalTrials.gov, number NCT01911897.
Between December, 2013, and February, 2016, 30 patients were enrolled and underwent successful implantation. Mean age was 52 years (SD 12), 15 patients (50%) were men, and mean antihypertensive use was 4·4 drugs (1·4). Mean office blood pressure was 184/109 mm Hg (18/14) at baseline and was reduced by 24/12 mm Hg (13–34/6–18) at 6 months (p=0·0003 for systolic and p=0·0001 diastolic blood pressure). Mean baseline 24 h ambulatory blood pressure was 166/100 mm Hg (17/14) at baseline and was reduced by 21/12 mm Hg (14–29/7–16) at 6 months (p<0·0001 for systolic and diastolic blood pressure). Five serious adverse events had occurred in four patients (13%) at 6 months: hypotension (n=2), worsening hypertension (n=1), intermittent claudication (n=1) and wound infection (n=1).
In patients with resistant hypertension, endovascular baroreceptor amplification with the MobiusHD device substantially lowered blood pressure with an acceptable safety profile. Randomised, double-blind, sham-controlled trials are warranted to investigate the use of this treatment further.
Vascular Dynamics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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