Observation Time Research Articles

Long‐Term Single‐Molecule Tracking in Living Cells Using Weak‐Affinity Protein Labeling

Single‐particle tracking (SPT) has become a powerful tool to monitor the dynamics of membrane proteins in living cells. However, permanent labeling strategies for SPT suffer from photobleaching as a major limitation, restricting observation times, and obstructing the study of long‐term cellular processes within single living cells. Here, we use exchangeable HaloTag Ligands (xHTLs) as an easy‐to‐apply labeling approach for live‐cell SPT and demonstrate extended observation times of individual live cells of up to 30 minutes. Using the xHTL/HaloTag7 labeling system, we measure the ligand‐induced activation kinetics of the epidermal growth factor receptor (EGFR) in single living cells. We generate spatial maps of receptor diffusion in cells, report non‐uniform distributions of receptor activation, and the formation of spatially confined ‘hot spots’ of EGFR activation. Furthermore, we measured the mobility of the ER‐luminal protein calreticulin in living cells and found diffusion coefficients that correlated with the ER nano‐structure. This approach represents a general strategy to monitor protein dynamics in a functional context and for extended observation times in single living cells.

Long-TermSingle-Molecule Tracking in Living Cells Using Weak-Affinity Protein Labeling.

Single-particle tracking (SPT) has become a powerful tool to monitor the dynamics of membrane proteins in living cells. However, permanent labeling strategies for SPT suffer from photobleaching as a major limitation, restricting observation times, and obstructing the study of long-term cellular processes within single living cells. Here, we use exchangeable HaloTag Ligands (xHTLs) as an easy-to-apply labeling approach for live-cell SPT and demonstrate extended observation times of individual live cells of up to 30 minutes. Using the xHTL/HaloTag7 labeling system, we measure the ligand-induced activation kinetics of the epidermal growth factor receptor (EGFR) in single living cells. We generate spatial maps of receptor diffusion in cells, report non-uniform distributions of receptor activation, and the formation of spatially confined 'hot spots' of EGFR activation. Furthermore, we measured the mobility of the ER-luminal protein calreticulin in living cells and found diffusion coefficients that correlated with the ER nano-structure. This approach represents a general strategy to monitor protein dynamics in a functional context and for extended observation times in single living cells.

How Skilful Are Cloud Cover Products in Representing Observed Cloudiness in Québec?

ABSTRACT In this study, we performed, for the first time, a detailed analysis of cloudiness in Québec using station based observations and evaluated the trustworthiness of various satellite and reanalysis based cloud cover products. We found only 12 stations with observational time series long enough for providing robust analysis due to various issues related to observing methods and recording of information during the 1990s. Our results showed that Québec can be fairly cloudy throughout the year with annual mean cloud cover fraction ranging between 0.5 and 0.7 with autumn being the cloudiest season at most station locations. We also found a significantly increasing trend in cloudiness in the winter season over Québec during 1982–2012 (∼2–6% per decade depending on the location). Among the cloudiness products evaluated in this study, a satellite based cloudiness product (i.e. based on AVHRR) performed best in representing the observed cloudiness over Québec including the wintertime increasing trend. Two reanalysis based cloudiness products (i.e. ERA5 and NARR) also performed well in representing the observed cloudiness indicated by high correlations, relatively lower mean biases and smaller root mean square errors. However, the reanalysis products did not capture well the observed seasonal trends. All products showed relatively larger biases in the winter season except JRA-25 reanalysis product. During the warmer months, however, JRA-25 showed largest biases followed by MERRA-2 reanalysis product. JRA-25 and MERRA-2 also had lower correlation for annual and winter means and highest root mean square errors for all seasons. Furthermore, based on two skill scores, we found that the ERA5, AVHRR and NARR performed relatively better than JRA-25 and MERRA-2. Based on these results we conclude that the satellite product and the two reanalysis products can be useful resources (as observational proxies) along with station based observations for understanding long term changes in cloudiness of this region and also potentially evaluating regional climate model simulations.

Duration of In-patient Physical Therapy at a Tertiary Hospital: Implications of a Time and Motion Study

Background and Objectives. Inpatient physical therapy (PT) care entails careful provision of service for individuals across a spectrum of disorders needing evidence-based physical rehabilitation during their hospital admission. The main difficulty is identifying adequate time allocation for safe patient service within an eight-hour working time frame. At a selected tertiary teaching government-run hospital, an arbitrary personnel-population ratio method is used for human resource allocation which may lead to issues in service delivery and healthcare workforce wellness. Apart from patient care, physical therapists also assume non-clinical roles revolving on administration, clinical education, and research. This highlights the importance of identifying the duration of tasks to assess work efficiency and manage time constraints posed by the limitations of the work shift. Practice guidelines may help improve staff workload scheduling, however, there is a lack of available guidelines regarding physical therapy practice in the hospital or acute care setting for developing countries. The purpose of this study was to determine the duration of care for inpatients with musculoskeletal and neurological conditions and administrative tasks, and to determine the relationship of duration of care with months of experience. Methods. A continuous observation time motion study of a typical workday of all physical therapists in an in-patient setting of a tertiary teaching hospital was conducted. An external observer will time the tasks done by the PT. The external observer kept distance from the direct patient encounter to minimize interference that may affect timing. Patients with conditions of different etiologies and functional levels were included. Results. Nineteen physical therapists with a mean experience of 54.63 months were observed. There were no adverse events during the implementation of this study. The total mean time in minutes of management of neurological patients is 37:32, and musculoskeletal patients is 28:30. Time for administrative tasks took an average of 20:33 minutes. There was also a low positive correlation on months of experience and treatment duration for patients with neurologic conditions (p=0.0471). Results showed that the allocated treatment duration is determined to be sufficient for performing PT activities. The optimal number of patients to be decked can also be appropriately determined to optimize resource allocation. Conclusion. Our pilot study attempted to quantify the duration of PT care in an inpatient setting that caters to patients with different diagnosis and varying needs for PT management. Although descriptive statistics and a weak to insignificant correlation was seen in most of the variables, there may be some benefit in gathering more duration data across different acute care settings within the country. Our pilot time and motion study can contribute to the limited evidence of duration of inpatient care that may inform human resource allocation, deliverables prioritization, and employee wellness and development. Figures have been presented which could be the basis for future policy research for management science and resource allocation studies.

2019odp -- A massive oxygen-rich Type Ib supernova

Stripped envelope (SE) supernovae are explosions of stars that have somehow lost most of their outer envelopes. We present the discovery and analyse the observations of the supernova 2019odp (a.k.a. ZTF19abqwtfu) covering epochs within days of the explosion to late nebular phases at 360\,d post-explosion. Our observations include an extensive set of photometric observations and low- to medium-resolution spectroscopic observations, both covering the complete observable time range. We analysed the data using analytic models for the recombination cooling emission of the early excess emission and the diffusion of the peak light curve. We expanded on existing methods to derive oxygen mass estimates from nebular phase spectroscopy, and briefly discuss progenitor models based on this analysis. Our spectroscopic observations confirm the presence of He in the supernova ejecta and we thus (re)classify SN 2019odp as a supernova . From the pseudo-bolometric light curve, we estimate a high ejecta mass of $M_ ej 4 - 7 M_ The high ejecta mass, large nebular O I Ca II $ line flux ratio ($1.2 - 1.9$), and an oxygen mass above $ 0.5\, M_ point towards a progenitor with a pre-explosion mass higher than $18\,M_ Whereas a majority of analysed SE supernovae in the literature seem to have low ejecta masses, indicating stripping in a binary star system, SN 2019odp instead has parameters that are consistent with an origin in a single massive star. The compact nature of the progenitor ($ 10\,R_ suggests that a Wolf-Rayet star is the progenitor.

Characteristics and Clinical Significance of Skull Defect Restoration in Young Patients: A Single-center Report and Literature Review.

The objective of this study is to observe cranial regeneration following cranial defects in young patients and analyze the factors influencing the regeneration process. In this retrospective study, a comparative and analytical assessment was conducted on the clinical data of 2 distinct cohorts: the observation group comprised patients aged ≤22 years with a regenerated cranial area ≥4cm2 following cranial defects, while the control group consisted of individuals with cranial defects persisting for over 1 year and a regenerated cranial area measuring <4cm2. These patients had been admitted to our department from August 2008 to October 2022. In addition, an analysis was undertaken to discern the pertinent factors influencing the process of cranial regeneration. Among the 32 patients in the observation group, 9 patients developed complications after decompressive craniectomy (DC) (hereafter referred to as post-DC complications); all the patients in this group, except one, underwent cranioplasty. The control group consisted of 12 patients, all of whom had post-DC complications and underwent cranioplasty; among them, 4 patients with a coexisting complication of hydrocephalus also underwent ventriculoperitoneal shunting. Cranial regeneration was observed in all 23 patients who did not have post-DC complications and in 9 of the 21 patients with post-DC complications. The rate of cranial regeneration was lower in the group with post-DC complications than in the group without post-DC complications, and the observation time (the time from cranial defect to the completion of cranioplasty) was longer in patients in the group with post-DC complications than those in the group without post-DC complications. Cranial bone regeneration can be achieved in young patients with cranial defects if factors favorable to cranial regeneration are effectively managed. These include preserving the dura mater, periosteum, and diploe during the surgery and maintaining good physical conditions postoperatively. The distribution pattern of the regenerated bones aligns with the shape of the flap. Post-DC complications represent adverse factors that can negatively affect cranial regeneration.

The Effect of Sampling Schedule on Assessment of Dietary Measures: Evidence From Blue Monkeys (Cercopithecus mitis stuhlmanni).

Accurately assessing primate diets is important in studies of behavioral ecology and evolution. While previous research has compared sampling methods (scan, focal), we examined how sampling schedule influences accuracy of dietary measures. We define sampling schedule as the combined distribution (random vs. consecutive) and frequency of sampling days within a given month. Under field conditions, time may be required to locate a study group, and we therefore also subtracted 1, 2, or 3 h from the beginning of all non-consecutive days in each sampling schedule to mimic observation time lost to search. From a dense (near daily) 5-year record of feeding behavior derived from focal animal follows of adult females in five wild blue monkey (Cercopithecus mitis) groups, we created data subsets matching various sampling schedules, and compared monthly dietary measures calculated from each subset to those based on the full data set. These measures included (1) the proportion of observation time feeding on fruit, (2) diet composition (three top-ranked food items), (3) species richness of plant diet, (4) Shannon-Wiener diversity index based on plant species, and (5) Holmes-Pitelka index expressing dietary overlap with the previous month. We used generalized linear mixed models to assess how frequency and sampling type (a combination of distribution and hours lost) relate to a subset's deviation from the full data set, where a smaller deviation (or higher chance of matching, for diet composition) implies greater accuracy. For all dietary measures, increasing observation frequency increased accuracy. The response to distribution varied among measures, but sampling types generally differed more at lower frequencies. Deviation varied widely within and between dietary measures, and some sampling schedules resulted in values with large percentage differences from the "full" data. Accordingly, when designing and comparing studies, researchers should consider how sampling schedules may influence the accuracy of the dietary measures of interest.

Cost minimization analysis of treatments for metastatic HER2-positive breast cancer in Peru: Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injections.

The main objective of this study is to determine whether the employment of fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC; and Phesgo as brand name) to treat metastatic HER2-positive breast cancer patients would minimize costs compared to the traditional treatment of separate intravenous doses of pertuzumab and trastuzumab in Peru. To achieve this, we used EsSalud (the social security health insurance) data and assessed it through a mixed strategy, which consisted of a quantitative and a qualitative approach. The first one aimed to calculate the direct (non-drug consumables, drugs, and healthcare professionals) and indirect costs of both treatments to develop a comparison, whilst the second aimed to validate information and internalize the procedure in an EsSalud context. Overall, we found that the usage of PH FDC SC would be cost saving in EsSalud's context. Specifically, we found three main advantages. Firstly, PH FDC SC generates a savings of 62% in non-drug consumables, which helps alleviate the healthcare system budget constraint. Secondly, its adoption frees up 61 hours of treatment and observation time for a single patient per year, which in turn increases the attention capacity of the healthcare system in terms of nursing hours and chemotherapy couches. Thirdly, the reduction of clinic time supposes an advantage for the patient in the form of increased productivity and well-being. Hence, the adoption of this drug would improve the quality of life of patients while reducing costs and pressure on the healthcare system. This is aligned with the strategy of prioritizing the appropriate breast cancer treatment within the National Cancer Care Plan. In this regard, we also found that the savings produced from switching from the traditional intravenous treatment to the subcutaneous one would allow EsSalud to afford full annual costs of 2 additional treatments, but without increasing their budget. This would cover 7% of the gap of 29 patients who do not have access to full treatment.

A Phase 2 Sensitivity and Selectivity Study of High-Dose 5-Aminolevulinic Acid in Adult Patients Undergoing Resection of a Newly Diagnosed or Recurrent Glioblastoma.

The utility of oral 5-aminolevulinic acid (5-ALA)/protoporphyrin fluorescence for the resection of high-grade gliomas is well documented, but the problem of false-negative observations remains. This study compares high-grade glioma visualization with low/standard dose 5-ALA (<30 mg/kg) to high-dose 5-ALA (>40 mg/kg) to see if by using this higher dose, it is possible to reduce the rate of false-negative observations without increasing the rate of false-positive (FP) observations and therefore increase the sensitivity. This is a prospective study of consecutive patients with radiological evidence of presumed high-grade glioma. We reviewed the data from patients who received preoperative low/standard doses and patients who received a preoperative high dose of 5-ALA. Adverse events, dose to observation time, intensity of tumor fluorescence, and results of biopsies in areas of tumor and tumor bed under deep blue light were recorded. A total of 22 patients with high-grade glioma received a dose >40 mg/kg (high-dose) and 9 patients received <30 mg/kg (low/standard dose). There were no serious adverse events related to 5-ALA in any subject. There was a very high sensitivity and specificity of 5-ALA for the presence of tumor in both groups. There were no FP observations (fluorescence with no tumor) in either group. The specificity and the positive predictive value were 100% in both groups. The sensitivity and the negative predictive value were 53.3% and 30.0% in the low/standard dose group and 59.5% and 31.8% in the high-dose group, respectively. High-dose oral 5-aminolevulinic/protoporphyrin fluorescence is a safe and effective aid to the intraoperative detection of high-grade gliomas with high sensitivity and specificity. False-negative observations with a high dose do not seem to be less than that with a low/standard dose. The rate of FP observations with both groups remains very low.

Head tilt in 6 Ankole-Watusi cattle (Bos taurus ankole) with chronic exudative cornual sinusitis.

Ankole-Watusi cattle, Bos taurus ankole, have a unique wide-based horn structure with a large communication to the frontal sinus compared to other cattle breeds. A total of 6 cases of cornual sinusitis presented at the Toronto Zoo and Disney's Animal Kingdom Lodge® and Disney's Animal Kingdom® Theme Park with a head tilt. Clinically, 4 of the 6 cases had concurrent otitis at the time of initial clinical observation. Medical management was the standard across all cases with limited surgical success in 2 cases. Due to intractable and progressive clinical signs despite treatment attempts, euthanasia and postmortem examinations were performed. All animals had gross and histologic evidence of cornual sinusitis with massive mucoid exudate in either 1 or both horns. Fluid accumulation and sinusitis within the cornual sinus should be considered a differential diagnosis in Ankole-Watusi cattle with a head tilt.

Two-dimensional ASEP model to study density profiles in CVD growth

The growth of two-dimensional (2D) transition metal dichalcogenides using chemical vapor deposition has been an area of intense study, primarily due to the scalability requirements for potential device applications. One of the major challenges of such growths is the large-scale thickness variation of the grown film. To investigate the role of different growth parameters computationally, we use a 2D asymmetric simple-exclusion process (ASEP) model with open boundaries as an approximation to the dynamics of deposition on the coarse-grained lattice. The variations in concentration of particles (growth profiles) at the lattice sites in the grown film are studied as functions of parameters like injection and ejection rate of particles from the lattice, time of observation, and the right bias difference between the hopping probabilities towards right and towards left) imposed by the carrier gas. In addition, the deposition rates at a given coarse-grained site is assumed to depend on the occupancy of that site. The effect of the maximum deposition rate, i.e., the deposition rate at a completely unoccupied site on the substrate, has been explored. The growth profiles stretch horizontally when either the evolution time or the right bias is increased. An increased deposition rate leads to a step-like profile, with the higher density region close to the left edge. In 3D, the growth profiles become more uniform with the increase in the height of the precursor with respect to the substrate surface. These results qualitatively agree with the experimental observations.

Retrospective Evaluation of Peri-Implant Marginal Bone Level of Reduced Diameter Implants by Mixed Model Analysis.

The goal of successful implant placement is to maintain a long-term stable marginal peri-implant bone level (MBL). This retrospective study investigated the MBL of reduceddiameter implants (RDI). The implants were analyzed in different indication in the context of various surgical and prosthetic treatment strategies using heterogeneous data from a private practice. Mixed model analysis was used to process the heterogeneous data structure. This method has not been a standard method of data analysis in implantology, and it shows considerable advantages over conventional variance analyses regarding data integration from outpatient practices. 123 patients were treated with 326 implants. 247 implants were diameter-reduced, the remaining 79 implants were standard implants (SDI) as patient related controls. The mean observation time was 24.4 months, and the maximum observation time 76.0 months. The peri-implant bone level of the implants was evaluated, while considering the diameter, as well as the time of implant placement, time of loading, extent of augmentation and localization of the implants. The data were evaluated after restructuring using mixed model analysis. No significant difference was found between the use of RDI or SDI in the analyzed indication. Furthermore, no significant difference was found for the implant placement time, loading time, and the use of two-stage augmentations regarding the stability of the peri-implant bone level. Narrow-diameter implants are a sufficient treatment option in horizontally deficient bone conditions. The use of diameterreduced implants in the posterior region shows promising results; 3.5mm diameter implants may be indicated considering the individual patient situation. The use of mixed model analysis for the evaluation of heterogeneous practice data can lead to a significant increase in the number of retrospective studies and data integration from practices, forming a sound basis for evidence-based dentistry.

Deciphering the molecular mechanism underlying morphology transition in two-component DNA-protein cophase separation.

Nucleic acid and protein co-condensates exhibit diverse morphologies crucial for fundamental cellular processes. Despite many previous studies that advanced our understanding of this topic, several interesting biophysical questions regarding the underlying molecular mechanisms remain. We investigated DNA and human transcription factor p53 co-condensates-a scenario where neither dsDNA nor the protein demonstrates phase-separation behavior individually. Through a combination of experimental assays and theoretical approaches, we elucidated: (1) the phase diagram of DNA-protein co-condensates at a certain observation time, identifying a phase transition between viscoelastic fluid and viscoelastic solid states, and a morphology transition from droplet-like to "pearl chain"-like co-condensates; (2) the growth dynamics of co-condensates. Droplet-like and "pearl chain"-like co-condensates share a common initial critical microscopic cluster size at the nanometer scale during the early stage of phase separation. These findings provide important insights into the biophysical mechanisms underlying multi-component phase separation within cellular environments.

Resilience to major life events: Advancing trajectory modeling and resilience factor identification by controlling for background stressor exposure.

Resilience has been defined as the maintenance or quick recovery of mental health during and after stressor exposure. One popular operationalization of this concept is to model prototypical trajectories of mental health in response to an adverse event, where trajectories of undisturbed low or rapidly recovering symptoms both comply with the resilience definition. However, mental health responses are likely also influenced by other stressors occurring before or during the observation time window. These "background" stressors may affect a person's assignment to a trajectory class. When using these classes as dependent variables to identify resilience-predictive factors, this may lead to false estimates. A new method to build exposure-controlled trajectories based on time courses of stressor reactivity (SR), rather than pure mental health scores, is demonstrated on a data set of 707 initially healthy participants living in Germany (67.33% female; Mage = 29.20, SD = 8.27). SR scores express individual deviations from the sample's normative mental health reaction to observed real-life stressors during the observation time window, thus accounting for individual differences in exposure to background stressors. The resulting trajectory models are plausible. In analyses additionally controlling for background stressors occurring before the observation time window (past life events), low SR trajectories are predicted by the well-documented resilience factor sense of coherence, suggesting construct validity. Further, they are associated with lower odds of developing categorical mental health conditions, suggesting predictive validity. Our study provides the first proof of principle for a refined method to identify predictors of resilience to major stressor events. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A search for water vapor plumes on Europa by spatially resolved spectroscopic observation using Subaru/IRCS

Abstract We present near-infrared high-dispersion spectroscopic observations of Europa using the Infrared Camera and Spectrograph (IRCS) onboard the Subaru Telescope, seeking direct evidence of water plumes on Europa and exploring spatial variations in plume activity. Using the high spectral/spatial resolution and sensitivity of Subaru/IRCS, our observations have enabled a spatially resolved search for water plumes on Europa. Within our detection limits and time of observation, we found no evidence for the presence of water emission. For a rotation temperature of 50 K, we derived an upper limit on the H$_{2}$O abundance of 9.46 $\times$ 10$^{19}$–5.92 $\times$ 10$^{20}$ m$^{-2}$ in each divided slit area and 4.61 $\times$ 10$^{19}$ m$^{-2}$ in the entire area covered by the slit. This upper limit lies below the inferred water abundance from previous UV observations by the Hubble Space Telescope, while being less sensitive by a factor of three compared to the Keck telescope and by one order of magnitude or more than the James Webb Space Telescope observations. Our results align with previous studies and demonstrate that using Subaru/IRCS is an effective strategy for searching for water plumes on Europa with high spatial resolution. Continued observations across different surface areas and orbital phases are essential to fully characterize Europa’s plume activity and complement upcoming space missions.

Baroreflex activation therapy in heart failure patients with reduced ejection fraction: a long-term follow up

Abstract Introduction Heart failure with reduced ejection fraction (HFrEF) is a major public health concern with substantial morbidity and mortality. Overactivation of the sympathetic nervous system is a key pathophysiological process driving heart failure progression. Baroreceptor activation therapy (BAT) targets this autonomic imbalance and is a promising treatment strategy for patients with HFrEF. Current short-term studies indicate that BAT provides symptomatic relief, improvement in left ventricular function and cardiac biomarkers. However, data regarding the long-term effect of BAT on HFrEF are scarce. Purpose This study aims to assess long-term outcome in HFrEF patients who underwent BAT. Methods Patients with HFrEF who received BAT between 2014-2023 were followed until latest available follow-up. Symptom burden, echocardiography and laboratory testing were assessed before BAT implantation and in subsequent follow ups. Results 23 patients (mean age 66±10 years, 83% men) with HFrEF were included in the study. Etiology of heart failure was ischemic in 70%. The majority of patients (96%) suffered from NYHA III with a mean left ventricular ejection fraction (LVEF) of 23±8% and NTproBNP of 2463±2922pg/ml. Complication occurred in one patient during BAT implantation (4%). Mean follow-up was 3±2 (max. 7.5) years. BAT reduced NYHA classification in 12 patients (52%) after 1 year, of which 1 patient remained in ameliorated NYHA for 7.5 years. Evolution of NYHA functional class over time is shown in Figure 1. Echocardiographic evaluation revealed significant improvement in LVEF of 9±9% after 1 year (p&amp;lt;0.001) and by 11±9% after 2 years (p=0.005). In long-term a trend towards improved LVEF could be observed (Figure 2). In addition, BAT mildly reduced NTproBNP in the first 2 years (after 1 year non-significantly by -396±1006pg/ml and significantly after 2 years by -566±651pg/ml (p=0.039)). Seven patients reaching recommended replacement time underwent device exchange. Four patients deceased during observation time. Conclusion BAT resulted in a substantial reduction in NYHA classification, improvement in LVEF, and a delayed reduction in NTproBNP levels. These findings highlight the long-term efficacy and potential benefits of BAT as a therapeutic intervention for patients with HFrEF.Sankey plot of NYHA class over timeAlteration of LVEF over time

Impact of intravascular imaging on mortality in patients undergoing left main coronary artery PCI. Propensity score matching analysis of the high-volume single centre registry

Abstract Background Recent guidelines endorsed use of intravascular imaging in left main coronary artery (LMCA) percutaneous coronary intervention (PCI). However, impact of adjunctive percutaneous imaging tools on mortality is ambiguous. Purpose The purpose was to investigate impact of intravascular imaging (IVI) on all-cause mortality in patients with LMCA disease. Methods Group of 998 individuals undergoing LMCA PCI was selected from medical records of patients hospitalized in years 2008-2022. Data on mortality were obtained from the Ministry of Digital Affairs. Overall observation time was 14 years (mean 4.3 years). Survival analysis was performed using Cox proportional hazard regression in the overall and propensity-score matched (PSM) population. Results The median age was 71 y.o. (IQR 16), 265 (41.0%) of patients presented with acute myocardial infarction and 183 (20.7%) had history of previous coronary artery bypass grafting (CABG). IVI-guided PCI was performed in 353 (35.4%) patients. In the overall unmatched population, IVI reduced one-year and long-term mortality by 70% (HR 0.3, 95% 0.19-0.47, P&amp;lt;0.001) and 57% (HR 0.43, 95% CI 0.34-0.55, P&amp;lt;0.001). In the subgroup analysis stratified on the history of previous CABG, in patients with unprotected LMCA, IVI resulted in 74% and 63% mortality reduction in the one-year and long-term follow-up (HR 0.26, 95% CI 0.16-0.42, P&amp;lt;0.001; HR 0.37, 95% CI 0.28-0.47, P&amp;lt;0.001; respectively). No influence of IVI on patients with previous CABG was observed. After PSM adjustment for baseline and angiographical characteristics, in the overall population IVI was still associated with significant one-year (HR 0.49, 95% CI 0.25-0.99, P=0.045) and long-term mortality reduction (HR 0.65, 95% CI 0.44-0.97, P=0.03). In patients with unprotected LMCA disease, IVI reduced mortality in two-year observation (HR 0.49, 95% CI 0.26-0.91, P=0.02) and long-term follow-up (HR 0.62, 95% CI 0.41-0.93, P=0.02), with no significant effect in one-year observation. No effect of IVI was observed in the PS-matched cohort of patients with previous CABG. Conclusions Intravascular imaging is associated with significantly better survival in patients undergoing LMCA PCI. The greatest benefit may be obtained in patients with no previous history of CABG. Further studies should investigate subgroups that benefit the most from adjunctive percutaneous tools.PS-matching detailsKaplan-Meier curves in subgroups

Long-term outcomes in women diagnosed with heart failure in connection to delivery

Abstract Background Heart failure (HF) among young patients may be from various causes, often triggered by heightened physical demands like pregnancy. Data regarding outcomes of women diagnosed with HF in conjunction to pregnancy and delivery are varied. There remains a notable gap in understanding the outcomes observed in women diagnosed with heart failure in conjunction with delivery. Also, long-term follow-up studies are crucial to elucidate the impact of pregnancy-associated HF on future cardiovascular. Purpose To study the interplay between pregnancy, HF, and subsequent cardiovascular risk. Method Using the personal identification numbers (PINs) that all individuals in Sweden have enables linkage of data between different registers. Data from the National Patient Register (NPR), Swedish Medical Birth Register (MBR) and the Cause of Death Register were also used. All women 18 to 50 years of age registered in the in MBR in the period 1st January 1997 to 31st December 2019 were included. Women with first-time HF in relation to delivery were identified using the international classification code for diseases (ICD-10) I50, I42, I43 and 090.3 together with co-morbidities. Every patient was compared with 5 controls without HF from the Total Population Register matched on age at delivery and calendar year of delivery. Outcomes: all-cause mortality, and any cardiovascular disease (CVD) diagnosed during the observation time. Results A total of 286 cases and 1,430 controls were included. The prevalence of comorbidities at baseline for both patients and controls was low; congenital heart disease (1.4%, vs. 0%), pulmonary hypertension (1.0% vs. 0%), valvular heart disease (5.9% vs. 0%), myocardial infarction 0.7% vs. 0%), arrhythmia (5.9% vs. 0%), hypertension (6.3 % vs. 0.1%), (all p&amp;lt;0.05). Preeclampsia prior to HF diagnosis had 31% of patients vs. 0.2% of controls (p&amp;lt;0.001). Patients exhibited higher mortality rates at 4.9% during median follow up 9.0 (IQR 5.6-13.0) years vs. 0.3%, median follow up 9.4 (6.2-13.5) years and hazard ratios (HR) for all-cause mortality HR (95% CI) of 18.20 (5.99 - 55.31) (p&amp;lt;0.001) compared to controls. During median follow up of 3.2 (0.0-9.2) years 60.1% of patients were diagnosed with CVD both at in-/out-patient settings compared with 4.1% in controls during 9.4 (5.8-13.5) years of follow up. Comparing patients with controls the HR (95% CI) was 22.24 (16.50 - 29.96) p&amp;lt;0.0001 for CVD diagnosis during follow-up, see Figure 1. Conclusion In conjunction with delivery, and in the years thereafter, women with heart failure diagnosis had more than eighteen times higher risk of mortality than women without heart failure. The risk of CVD event in the heart failure group is highest in conjunction with delivery. Figure 1. Cumulative incidence functions for all-cause mortality, CVD in- or out-patient visit adjusted for death as competing risk, comparing cases with controls.

Fractional flow reserve versus solely angiography-guided revascularisation in coronary artery disease, systematic review and meta-analysis

Abstract Objective Subsequent randomised controlled trials (RCTs) comparing the clinical outcomes of fractional flow reserve (FFR)-guided and angiography-guided revascularisation in patients with coronary artery disease (CAD) yielded inconsistent results. Moreover, recent European Society of Cardiology (ESC) guidelines lowered recommendation for FFR use in acute coronary syndorme (ACS). This study aimed to assess head to head whether FFR-guided revascularisation reduces the rates of hard clinical endpoints in comparison with the angiography-guided approach alone. Methods A systematic review was conducted through October 2023 at Embase, Clinicaltrials.gov, Cochrane Library, and EBSCO. Only RCTs that evaluated stable and unstable CAD and acute myocardial infarction (MI) were included. The trials selection was performed according to the latest ESC guidelines. Meta-regression analysis was performed to assess the impact of observation time on outcomes. Results Overall, 11 571 records were screened for relevant studies. Eight RCTs involving 4713 patients were included in the meta-analysis. FFR guidance was associated with a significant reduction of MI (RR, 0.75 [95% confidence interval {Cl}, 0.58–0.96], p=0.02) and lower rate of revascularisation (standardised mean difference - 0.12, [95% Cl, -0.14–-- 0.09], p&amp;lt;00001). There were no differences between FFR-guided and angio-guided revascularisation in MACE (RR, 0.84 [95% Cl, 0.69–1.02], p=0.08), all-cause mortality (RR, 1.00 [95% Cl, 0.58–1.74], p=0.99), and unplanned revascularisation (RR, 0.89 [95% Cl, 0.72–1.10], p=0.28). The meta-regression analysis revealed a significant impact of the duration of follow-up for MACE, all-cause mortality and MI, but not for unplanned revascularisation. Conclusions FFR-driven revascularisation was associated with a significantly lower rate of MI for entire population and also in the ACS subset. These results were achieved with a substantially less revascularisations compared with solely angiographic guidance.

Prevention of mechanical valve thrombosis with a combination of the factor Xa inhibitor edoxaban plus aspirin in swine: intermediate results from the EdoValves project

Abstract Background Patients with an implanted mechanical heart valve (MHV) currently have a contraindication to the use of non-vitamin K antagonist oral anticoagulants (NOACs) based on the unfavorable results of the RE-ALIGN trial with dabigatran. We hypothesized that the combination of a Factor Xa inhibitor, acting upstream of thrombin generation, plus aspirin, may effectively prevent valve thrombosis, providing a much more friendly and viable alternative to vitamin K antagonists for such patients. We tested this in a swine model with a recently implanted mechanical valve prosthesis in the mitral position, combining the most unfavorable conditions promoting mechanical valve thrombosis, based on (a) the implanting position; (b) recent surgery; (c) the high thrombogenicity of the animal model. The study was approved by the Animal Ethics Committee of the University of Pisa and the Italian Ministry of Health and conducted according to Good Clinical Practices for Animal Experiments. Methods 17 farm male pigs, weighing ≈30 kg at the beginning, underwent cardiac surgery under general anesthesia and with extracorporeal circulation to receive a 25 mm or 27 mm bileaflet Corcym Bicarbon mechanical heart valve replacement in the mitral position. Pigs were given 1 mg/kg enoxaparin immediately after surgery and started with the oral daily administration of edoxaban 1 mg/kg (30 mg, then escalated to 60 mg with the animal growth) + aspirin 100 mg, both given as crushed tablets with a food pellet since the animal awakening from anesthesia. An initially planned warfarin control group was quickly abandoned because of the extreme difficulty of controlling warfarin activity. Animals were submitted to blood sampling and transthoracic echocardiography at least twice in the follow-up when uneventful for up to three months or in case of health deterioration. The autopsy was performed by a certified pathologist after each spontaneous death or procured sacrifice. Results (Figure 1): Excluding 5 peri-operative deaths, 12 animals survived surgery. Of those, 6 died within the second month: pulmonary edema occurred in 3 cases, due to prosthesis-mismatch in the growing animals; pulmonary infection occurred in 1 subject; heart failure due to valve thrombosis occurred in 2 cases. Six swine were full-term survivors in good health status up to the 3-month planned observational time. No hemorrhagic events were ever documented. Conclusion The combination of edoxaban + aspirin effectively avoided valve thrombosis events in 10 out of 12 (83%) analyzable animals and was safe from bleeding complications. The study is ongoing up to a predicted sample size of ≥20 animals. If further confirmed, these data may open the possibility of an alternative to vitamin K antagonists in humans with the fixed-dose drug combination here used, without the need for continuous anticoagulation monitoring and with expected greater safety.Figure 1