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Electrocardiographic screening before subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation is unsuccessful in around 10% of cases. A personalized screening method, by slightly moving the electrodes, to obtain a better R/T ratio has been described to overcome traditional screening failure. The objectives of the SIS study were to assess to what extent a personalized screening method improves eligibility for S-ICD implantation and to evaluate the inappropriate shock rate after such screening success. All consecutive patients eligible for an S-ICD implantation were prospectively recruited across 20 French centers between December 2019 and January 2022. In case of traditional screening failure, patients received a second personalized screening. If at least 1 vector was positive, the personalized screening was considered successful, and the patient was eligible for implantation. The study included 474 patients (mean age, 50.4 ± 14.1 years; 77.4% men). Traditional screening was successful in 456 (96.2%) cases. This figure rose to 98.3% (n = 466; P =.002) when personalized screening was performed. All patients implanted after successful personalized screening had correct signal detection on initial device interrogation. Nevertheless, after 1-year follow-up, 3 of the 7 patients (43%) implanted with personalized screening experienced inappropriate shock vs 18 of the 427 patients (4.2%) with traditional screening and S-ICD implantation (P =.003). Traditional S-ICD screening was successful in our study in a high proportion of patients. Considering the small improvement in success of screening and a higher rate of inappropriate shock, a strategy of personalized screening cannot be routinely recommended. ClinicalTrials.gov identifier: NCT04101253 [Display omitted] [ABSTRACT FROM AUTHOR]

Thromboembolic events, particularly strokes, remain a major complication of transcatheter aortic valve replacement (TAVR). Embolic protection devices have failed to show significant clinical benefit in large randomized clinical trials. Aortic wall thrombus (AWT) is often observed on multidetector computed tomography during TAVR work-up, but its prognostic significance is uncertain. This study sought to evaluate the association between the presence of AWT and the incidence of thromboembolic outcomes in patients undergoing transfemoral (TF) TAVR for severe aortic stenosis. This was a prospective cohort study of consecutive patients who underwent TF TAVR for severe aortic stenosis between January 2011 and April 2022. A dedicated scale (range: 0-10) was qualitatively used to assess AWT. The primary outcome was a composite of procedural thromboembolic events defined as ischemic stroke, blue toe syndrome, bowel ischemia, or other solid organ infarction. The secondary endpoints were ischemic strokes and procedural death. Of the 641 patients included, severe AWT (score ≥8) was identified in 73 (11.4%). The presence of severe AWT was strongly associated with an increase in the primary outcome (OR: 8.48; 95% CI: 3.36-21.40; P < 0.001). This relationship persisted following multivariable analysis, which adjusted for comorbidities and procedural characteristics. The presence of severe AWT was also found to be associated with an increased incidence of stroke and procedural death (OR: 5.66; 95% CI: 2.00-15.30; P = 0.002 and OR: 4.66; 95% CI: 1.80-11.30; P = 0.002, respectively). The presence of severe AWT on preprocedural multidetector computed tomography is strongly associated with thromboembolic complications including stroke and mortality after TF TAVR. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • 34S-enrichments in pyrites associated with regressions in the Ediacaran record. • Regressive stages triggered sulfate distillation in West Gondwana basins. • Enhanced distillation and euxinia in interior seas precluded benthic habitability. The late Ediacaran record encompasses frequent occurrences of 34S-enriched pyrites, which can surpass the coexisting sulfate isotope values. Deciphering what controls this marine isotope record is important to understand its biogeochemical implications, especially considering the early metazoan evolution. We present here multiple sulfur isotope compositions from pyrites of two distinct geotectonic settings within the late Ediacaran-early Cambrian West Gondwana, allowing to constraint spatial and temporal distribution of 34S-enrichments. The Tamengo Formation represents a carbonate-siliciclastic ramp at Gondwana's continental margin, whereas the Bambuí Group records an epeiric sea within the core of this supercontinent. Both units display positive δ34S py excursions matching regressive trends (δ34S py up to 51 ‰), with a drop in δ34S py values associated with transgressions. A scenario of sulfate-distillation events throughout regressions is supported by the multiple sulfur isotope data, after transgressive events that episodically recharged sulfate in these environments. However, in the epicontinental Bambuí sea, δ34S py, Δ33S py and Δ36S py values suggest almost quantitative conversion of the initial sulfate into sulfide at the end of regressive stage, forced by enhanced stratification and inefficient circulation within continental areas. In this case, widespread toxic euxinic conditions were developed in inland seas, accompanied by methanogenesis, which resulted in highly 13C-enriched DIC due to methanogenic CO 2 , as recorded in the Bambuí Group. In the Tamengo ramp, on the other hand, sulfate levels would have not been completely consumed due to more frequent and efficient mixing with open waters, preventing perturbations in the carbon cycling and representing more favorable conditions to metazoan colonization, considering the abundant metazoan fossil record in this unit. The studied basins illustrate how 1st-order tectonic cycles may have been the major player over remarkable 34S-enrichments in pyrite for specific time intervals of the sedimentary record, through supercontinent assembly and expansion of restricted settings more prone to sulfate distillation. [ABSTRACT FROM AUTHOR]

While several scoring systems have been developed to predict short-term outcome in out-of-hospital cardiac arrest patients, there is currently no dedicated prognostic tool for drowning-associated cardiac arrest (DACA) patients. Patients experiencing DACA from two retrospective multicenter cohorts of drowning patients were included in the present study. Among the patients from the development cohort, risk-factors for day-28 mortality were assessed by logistic regression. A prediction score was conceived and assessed in patients from the validation cohort. Among the 103 included patients from the development cohort, the day-28 mortality rate reached 51% (53/103). Identified independent early risk-factors for day-28 mortality included cardiopulmonary resuscitation duration longer than 20 min (OR 6.40 [95% CI 1.88–23.32]; p = 0.003), temperature at Intensive Care Unit admission <34 °C (OR 8.84 [95% CI 2.66–32.92]; p < 0.001), need for invasive mechanical ventilation (OR 6.83 [95% CI 1.47–40.87]; p = 0.02) and lactate concentration > 7 mmol/L (OR 3.56 [95% CI 1.01–13.07]; p = 0.04). The Area Under the ROC Curve (AUC) of the developed score based on those variables reached 0.91 (95% CI, 0.86–0.97). The optimal cut-off for predicting poor outcomes was 4 points with a sensitivity of 92% (95% CI, 82–98%), a specificity of 82% (95% CI, 67–91%), a positive predictive value (PPV) of 84% (95% CI, 72–95%) and a negative predictive value (NPV) of 91% (95% CI, 79–96%). The assessment of this score on the validation cohort of 81 patients exhibited an AUC of 0.82. Using the same 4 points threshold, sensitivity, specificity, PPV and NPV values of the validation cohort were: 81%, 67%, 72% and 77%, respectively. In patients suffering from drowning induced initial cardiac arrest admitted to ICU with a DACA score ≥ 4, the likelihood of survival at day-28 is significantly lower. Prospective validation of the DACA score and assessment of its usefulness are warranted in the future. [ABSTRACT FROM AUTHOR]

Additive manufacturing (AM), often referred to as 3D printing, is a manufacturing technique that involves the creation of complex objects layer-by-layer while providing design flexibility. The broad spectrum of additive manufacturing applications in aerospace, medicine, automotive industries, etc., using high-value materials necessitates a precise final product with minimal wastage. However, the print's dependence on optimizing parameters such as nozzle diameter, printing speed, extrusion speed, nozzle temperature and other multifaceted factors can contribute to deviations from the intended design. This paper introduces a closed-loop in-situ assessment of layer height deviations using point cloud data to ensure real-time printed part modification. The printing is done using a direct-fed pellet screw extruder mounted on top of 6 degrees of freedom robotic arm. A structured light 3D scanner is used to obtain point cloud data. A Robot Operating System (ROS) based digital toolchain is employed to have seamless communication between all nodes of the AM system. The layer-by-layer printing is observed using an in-house CAM solution, which examines the point cloud data and compares it to the original CAD model. The deviations are analyzed, and the path of the next layer is re-planned to adjust for the digression in the previous layer. This control loop ensures that the final product meets the desired quality standards at minimum cost and efficient time and increases the opportunity for rapid prototyping and iterative design improvements. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a well-recognized opportunistic pathogen frequently responsible for hospital-acquired infections. Acquisition routes of P aeruginosa are both endogenous and exogenous, including transmission from a portion of the hospital water system. The impact of disinfection procedures of the water system and description routes of P aeruginosa transmission in a surgical intensive care unit over a 2-year period were investigated. Two distinct periods A and B were considered, respectively, before and after the disinfection. Fourier transform infrared spectroscopy was used to compare isolates recovered from patients and tap water. Overall, 21.3% of tap water samples were positive but with a significantly lower rate in period B. Concomitantly, the prevalence of patients positive for P aeruginosa decreased from 2.6% to 1%, suggesting a correlation between the presence of environmental sources and patient contaminations. The results revealed that 18% of patients were involved in cross-transmission events not related to any isolate recovered from water, suggesting transmission through care practices. Conversely, only 1 environmental transmission event was suspected in a patient. Although the link between the hospital environment and patients was unclear, HCW-associated care practices could be related to contaminated point-of-use waters and then indirect spreading to patients. • Pseudomonas aeruginosa ICU-acquired infections, with environmental origin suggested. • Maintenance operations on the water system. • Positive P aeruginosa tap water samples decreased after maintenance. • Reduction of P aeruginosa -positive patients decreased after maintenance operations. • Typing methods and epidemiological data suggesting rather transmission through care practices. [ABSTRACT FROM AUTHOR]

This pilot study explored the feasibility of a Forever Heart Program and the impact it has on oncology nurses' perception of the dying experience and their own compassion competence. Guided by Kubler-Ross's framework, the Forever Heart Program consists of a gemstone keepsake offered to patients and families during end-of-life care to support the grieving process. A mixed-methods approach utilized pretest/posttest design in a convenience sample of oncology nurses in an academic medical center over a 3-month period. The study collected demographics, Compassion Competence Scale scores, and qualitative responses via survey and an optional focus group. Twenty-five nurses participated in the presurvey, and 14 participated in the postsurvey. Seven nurses attended the focus groups. Overall, compassion competence scores were high, both pre and post. Qualitative themes included appreciation, connection, positive nursing, patient and family experience/relationships, grieving guidance, program benefits, and process opportunities. Although the study did not show statistically significant differences in compassion, it did show program feasibility and the potential positive impact that keepsakes like the Forever Heart Program can have on nurses and their role in the dying experience. [ABSTRACT FROM AUTHOR]

In primary biliary cholangitis (PBC), static liver stiffness measurement (LSM) has proven prognostic value. However, the added prognostic value of LSM time course in this disease remains uncertain. We conducted an international retrospective cohort study among patients with PBC treated with ursodeoxycholic acid and followed by vibration-controlled transient elastography between 2003 and 2022. Using joint modeling, the association of LSM trajectory and the incidence of serious clinical events (SCE), defined as cirrhosis complications, liver transplantation, or death, was quantified using the hazard ratio and its confidence interval. A total of 6362 LSMs were performed in 3078 patients (2007 on ursodeoxycholic acid alone; 13% with cirrhosis), in whom 316 SCE occurred over 14,445 person-years (median follow-up, 4.2 years; incidence rate, 21.9 per 1000 person-years). LSM progressed in 59% of patients (mean, 0.39 kPa/year). After adjusting for prognostic factors at baseline, including LSM, any relative change in LSM was associated with a significant variation in SCE risk (P <.001). For example, the adjusted hazard ratios (95% confidence interval) associated with a 20% annual variation in LSM were 2.13 (1.89–2.45) for the increase and 0.40 (0.33–0.46) for the decrease. The association between LSM trajectory and SCE risk persisted regardless of treatment response or duration, when patients with cirrhosis were excluded, and when only death or liver transplantation was considered. Tracking longitudinal changes in LSM using vibration-controlled transient elastography provides valuable insights into PBC prognosis, offering a robust predictive measure for the risk of SCE. LSM could be used as a clinically relevant surrogate end point in PBC clinical trials. [Display omitted] [ABSTRACT FROM AUTHOR]

Transvenous lead failure associated with cardiac pacing and defibrillation remains an important clinical problem, with an estimated incidence between 1 to 2%. Oversensing of non-physiological signals usually precede lead impedance changes and may result in clinical compliations such as pacing inhibition and inappropriate shocks. Device based algorithms that identify non-physiological signals can be used in conjunction with remote monitoring to facilitate early diagnosis and management of lead failure and avoid serious adverse outcomes. This review highlights mechanisms of lead failure and proposes a diagnostic approach to suspected lead failure. [ABSTRACT FROM AUTHOR]

[Display omitted] • Rehospitalization is a frequent and serious complication in patients with HF. • The CardioMEMS™ HF System is an invasive remote monitoring device. • The CardioMEMS™ HF System is known to reduce HFHs significantly. • COAST: open-label safety and effectiveness study with CardioMEMS™ HF System. • 103 patients were included in the French cohort of COAST. • No device/system complications or pressure sensor failures 2 years after implant. • 50.3% reduction in risk of HFH in the year after implant versus the year before. Previous studies have demonstrated the benefit of a haemodynamic-guided management strategy with the CardioMEMS™ HF System. No data from French patients have been published. To analyse the feasibility, safety and clinical benefit of the CardioMEMS™ HF System in 103 French patients included in the CardioMEMS HF System Post-Market Study (COAST). Prospective open-label cohort of New York Heart Association class III patients with at least one heart failure hospitalization in the 12 months before enrolment, regardless of left ventricular ejection fraction. The primary safety endpoints assessed the freedom from device/system-related complications and from pressure sensor failure at 2 years after implantation. The primary efficacy endpoint was evaluated comparing the rate of heart failure hospitalization during the year before and the year after implantation. At 2 years, there were no device/system-related complications or pressure sensor failures (P < 0.0001). There were 179 heart failure hospitalizations in the year before implantation compared with 79 in the year after implantation (risk reduction 50.3%; rate ratio 0.50, 95% confidence interval 0.38–0.66; P < 0.0001). During the 2 years of follow-up, pulmonary artery pressures were lowered significantly (mean pulmonary artery pressure –3.7 ± 6.3 mmHg; P < 0.0001), with a significant improvement in functional class and quality of life. In the French cohort of the COAST study, we have demonstrated that the CardioMEMS™ HF System is a reliable device, with no device/system-related complications or pressure sensor failures. Patients in this open-label cohort had a significant reduction in pulmonary artery pressures, with an improvement in New York Heart Association classification and quality of life, and a 50% reduction in the heart failure hospitalization rate in the year following implantation compared with the previous year. [ABSTRACT FROM AUTHOR]

To determine 10 MV IMRT and VMAT based protocols with a daily bolus targeting a skin dose of 45 Gy in order to replace the 6 MV tangential fields with a 5 mm thick bolus on alternate days method for post-mastectomy radiotherapy. We measured the mean surface dose along the chest wall PTV as a function of different bolus thicknesses for sliding window IMRT and VMAT plans. We analyzed surface dose profiles and dose homogeneities and compared them to our standard 6 MV strategy. All measurements were performed on a thorax phantom with Gafchromic films while dosimetric plans were computed using the Acuros XB algorithm (Varian). We obtained the best compromise between measured surface dose (mean dose and homogeneity) and skin toxicity threshold obtained from the literature using a daily 3 mm thick bolus. Mean surface doses were 91.4 ± 2.8% [85.7% – 95.4%] and 92.2 ± 2.3% [85.6% – 95.2%] of the prescribed dose with IMRT and VMAT techniques, respectively. Our standard 6 MV alternate days 5 mm thick bolus leads to 89.0 ± 3.7% [83.6% – 95.5%]. Mean dose differences between measured and TPS results were < 3.2% for depths as low as 2 mm depth. 10 MV IMRT-based protocols with a daily 3 mm thick bolus produce a surface dose comparable to the standard 6 MV 5 mm thick bolus on alternate days method but with an improved surface dose homogeneity. This allows for a better control of skin toxicity and target volume coverage. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The Alzheimer's Prevention Initiative (API) Generation Studies evaluated the BACE inhibitor umibecestat for Alzheimer's disease (AD) prevention. The studies were terminated early, and the reversibility of umibecestat's side effects was assessed. METHODS: Cognitively unimpaired 60‐ to 75‐year‐old apolipoprotein E (APOE) ε4 homozygotes and heterozygotes (the latter with elevated brain amyloid deposition) (n = 1556) received umibecestat (50 or 15 mg daily) or placebo for 7 months on average and were followed for a median (interquartile range) of 4 (3 to 6) months after washout. RESULTS: Compared to placebo, umibecestat‐treated participants had small, non‐progressive, but statistically significant decline in performance on certain cognitive batteries including Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and API Preclinical Composite Cognitive test, but not Clinical Dementia Rating‐Sum of Boxes. RBANS differences were no longer significant at the end of follow‐up. DISCUSSION: In people at genetic risk for AD, high‐dose beta‐site amyloid precursor protein cleaving enzyme (BACE) inhibition was associated with early mild cognitive worsening, which reversed shortly after washout, suggesting a symptomatic side effect not associated with neurodegeneration. Fully anonymized data, images, and samples are available upon request for further research on BACE inhibition. Highlights: This is the first trial with blinded assessment of reversibility of BACE inhibitor side effects.Umibecestat was tested in cognitively unimpaired persons at genetic risk for AD.Umibecestat led to early mild cognitive decline that reversed shortly after washout.This suggests a potentially manageable effect not associated with neurodegeneration.Further research may determine the future of BACE inhibition in AD prevention. [ABSTRACT FROM AUTHOR]

The micro-pipette aspiration technique is a classical experiment used to characterize the physical properties of inert fluids and biological soft materials such as cellular aggregates. The physical parameters of the fluid, as viscosity and interfacial tension, are obtained by studying how the fluid enters the pipette when the suction pressure is increased and how it relaxes when the suction pressure is put to zero. A mathematical model representative of the experiment is needed to extrapolate the physical parameters of the fluid-like matter; however, for biological materials as cells or cell aggregates mathematical models are always based on strong starting hypotheses that impact the significance of the identified parameters. In this article, starting from the bi-constituent nature of the cell aggregate, we derive a general mathematical model based of a Cahn–Hilliard–Navier–Stokes set of equations. The model is applied to describe quantitatively the aspiration-retraction dynamics of a cell-aggregate into and out of a pipette. We demonstrate the predictive capability of the model and highlight the impact of the assumptions made on the identified parameters by studying two cases: one with a non-wetting condition between the cells and the wall of the pipette (classical assumption in the literature) and the second one, which is more realistic, with a partial wetting condition (contact angle θ s = 150°). Furthermore, our results provide a purely physical explanation to the asymmetry between the aspiration and retraction responses which is alternative to the proposed hypothesis of an mechano-responsive alteration of the surface tension of the cell aggregate. Our study introduces a general mathematical model, based on the Cahn-Hilliard-Navier-Stokes equations, tailored to model micro-pipette aspiration of cell aggregates. The model accounts for the multi-component structure of the cell aggregate and its intrinsic viscoelastic rheology. By challenging prevailing assumptions, particularly regarding perfect non-wetting conditions and the mechano-responsive alteration of cell surface tension, we demonstrate the reliability of the mathematical model and elucidate the mechanisms at play, offering a purely physical explanation for observed asymmetries between the aspiration and retraction stages of the experiment. [Display omitted] [ABSTRACT FROM AUTHOR]