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Periprocedural Myocardial Infarction After Coronary Artery Bypass Grafting:Current Clinical Practices and Future Perspectives
No full textObjectives: The definitions of periprocedural myocardial infarction (PMI) after coronary artery bypass grafting (CABG) are heavily debated. A European Association for Cardiothoracic Surgery (EACTS)-endorsed international survey was conducted to evaluate current clinical practices and to reach a consensus-based agreement on the diagnostic characteristics required for a potential future PMI definition. Methods: The questionnaire complied with the CHERRIES guideline. A pilot version underwent iterative testing. The final version was distributed to all members of EACTS and allied specialties. The questionnaire evaluated definitions, biomarkers, and required diagnostic accuracy and was distributed between August-November 2024. Results: The questionnaire was completed by 175 respondents (surgeons: 71.4%, cardiologists: 20.6%, intensivists: 5.1%, other: 2.9%) from 29 countries. A specific definition of PMI was used by 46.4% of respondents (Universal Definition of Myocardial Infarction [UDMI]-4: 67.4%, Society of Cardiovascular Angiography and Interventions [SCAI]: 16.3%, second Academic Research Consortium [ARC-2]: 6.1%, other: 10.2%). Respondents identified biomarker concentrations defining PMI with supporting (imaging) evidence (high-sensitivity cardiac troponin T [hs-cTnT]: 489 ng/L, high-sensitivity cardiac troponin I [hs-cTnI]: 425 ng/L, CKMB-mass: 90ug/L, CKMB-activity: 100 U/L) and without (hs-cTnT: 931 ng/L, hs-cTnI: 1458 ng/L, CKMB-mass: 100ug/L, CKMB-activity: 300UL). The lowest acceptable sensitivity and specificity thresholds for a future definition were 95% [90%-95%] and 90% [80%-95%], respectively, while sensitivity was deemed more important than specificity (79.8% vs 20.2%, P < .001). Conclusions: The use of PMI definitions varies widely, though UDMI-4 is most frequently employed. Our findings highlight the need for a standardized, CABG-specific PMI definition with robust diagnostic accuracy to enable consistent diagnoses and a common clinical language
Higher cost, comparable outcomes:A health economic evaluation of patient-specific instrumentation vs. conventional instrumentation for total knee arthroplasty in a Dutch aging population
No full textPurpose: The demand for treatment of knee osteoarthritis is rising as the population ages. To optimise outcomes of total knee arthroplasty (TKA), several innovative techniques have been introduced, including patient-specific instrumentation (PSI). While these developments may improve clinical outcomes, they are often associated with higher healthcare costs. The present study aimed to evaluate the long-term cost-utility of PSI compared to conventional instrumentation (CI) for TKA, from a hospital perspective. Methods: A multicenter randomised controlled trial including 180 patients was conducted in 2010, with 45 patients in each treatment arm per center. For the current economic evaluation, data from one participating center (n = 90) were analysed. Patients were assigned to receive either PSI or CI TKA and completed EQ-5D-5L questionnaires preoperatively and at 5- and 10-year follow-up. Utility scores and Quality-Adjusted Life Years (QALYs) were derived from these questionnaires. Hospital records provided cost data, which were indexed to 2023 values. Incremental cost-effectiveness ratios (ICERs) were calculated as cost per QALY gained. Results: At final follow-up, 23 patients (26%) were lost due to death (n = 15, 17%) or withdrawal (n = 8, 9%). The cohort included 58% females with a mean age of 67 years. QALY gains did not differ significantly between groups at either follow-up point. Mean total costs were €10,722.58 per patient for PSI and €10,063.89 for CI, with PSI exceeding CI by €658.69. This translated into an ICER of €14,856.07/QALY after 5 years and €12,836.66/QALY after 10 years for PSI, compared to €13,932.24/QALY and €12,550.40/QALY, respectively, for CI. Conclusion: Both PSI and CI TKA improved quality of life at 5 and 10 years postoperatively. However, PSI incurred higher costs without demonstrating additional clinical benefit. From a hospital perspective, CI remains the more cost-effective approach. Level of Evidence: Level II, retrospective study of an RCT.</p
From symptom to disease:a Fleckian comparative epistemology of the conceptualization of chronic pain
No full textAlthough pain is considered a central object of medicine, it remains poorly under-stood. This is especially true for chronic pain conditions, in which an underlying cause often cannot or can no longer be found. Over the past decades, new scien-tific, technological, and social developments have led to the reconceptualization of chronic pain. In the latest edition of the International Classification of Diseases (ICD-11), chronic pain conditions are ascribed to a separate nosological category. Importantly, cases of chronic primary pain are now defined as a 'disease in its own right'. This is in stark contrast to how pain has traditionally been understood in medicine: as a symptom/sign of tissue damage. While this conceptual shift is con-sidered an important landmark in pain medicine, the reconceptualization of chronic pain has also been criticized. This is especially so because the conceptual shift was primarily explained by its practical benefits, while the etiology and patho-physiological mechanism remain unclear. Hence, the disease status of chronic pain remains unclear. In this paper, we argue that the understanding of chronic pain as a disease can be defended from a philosophical pragmatist perspective. By looking through the lens of philosopher of science Ludwik Fleck, we demonstrate that (1) the problematic status of chronic pain is historically contingent upon the mecha-nistic 'Cartesian' conceptualization of pain, but not problematic in itself; and (2), the view of chronic (primary) pain as a disease in its own right can be justified on pragmatist ground
Interobserver agreement in BPPV diagnosis using eye movement recordings
No full textBenign Paroxysmal Positional Vertigo (BPPV) is one of the most prevalent peripheral vestibular disorders seen in specialized dizziness clinics. Despite being a well-understood condition with effective treatment options, BPPV remains associated with significant diagnostic delays and healthcare costs. If proven reliable, telemedicine approaches could help address these challenges by improving diagnostic accessibility and efficiency. To investigate the interobserver agreement in BPPV diagnosis, when using eye movement recordings. Six vestibular medicine specialists (Specialist 1, 2, 3, 4, 5, 6) were recruited to participate in this study. The specialists were asked to evaluate the recordings of 240 patient cases who underwent assessment for BPPV (first assessment). After viewing the recordings of each case, they were required to make a BPPV diagnosis. Five specialists (2, 3, 4, 5, 6) agreed to repeat the procedure twice, to additionally evaluate the intraobserver agreement (second assessment). The proportion of agreement and Cohen's kappa were calculated for both interobserver and intraobserver agreement. Furthermore, agreement with the original diagnoses was evaluated. The interobserver agreement between experts was fair to moderate with a Cohen's kappa value of 0.40 (CI 95% [0.35, 0.45]) and a proportion of agreement of 60% (CI 95% [54, 67]). Specialists 2, 4, and 5 exhibited substantial intraobserver agreement. In contrast, Specialist 3 demonstrated fair intraobserver agreement, while Specialist 6 showed almost perfect intraobserver agreement. Regarding the first assessment, agreement with the original diagnoses ranged from fair to substantial, with kappa values between 0.40 and 0.70, and corresponding percentages between 58 and 78%. Similar results were observed for the second assessment. The interobserver agreement between specialists diagnosing BPPV using eye movement recordings, was fair to moderate. The suboptimal agreement could be related to missing clinical information (e.g. patient history and symptoms during positional maneuvers). Future studies should incorporate this information and reassess interobserver agreement
Light-Gated Amine Exchange in Diarylethene-Crosslinked Microgels
No full textThe functionalization of microgels with photoswitchable moieties enables the construction of multi-responsive systems, which are highly interesting for biological applications, for example, in drug delivery. Controlling the reversible uptake of functional molecules, however, remains a major challenge. To address this, we developed a novel aniline-type diarylethene (DAE) crosslinker and prepared a series of corresponding poly(N-vinylcaprolactam)-based microgels with varying degrees of DAE crosslinker. Upon UV light irradiation, the aniline (and thus enamine) motif of the DAE is converted to its imine form, thus allowing for reversible exchange with primary amines. Irradiating the DAE with blue light covalently locks the equilibrium and traps the amine in the microgels. The light-controlled covalent binding of fluorinated, hydrophobic, and hydrophilic amine derivatives was proven by dynamic light scattering and 19F NMR spectroscopy. Importantly, the impact of photoisomerization and amine binding on microgel properties was investigated and we were able to remotely control size as well as temperature and pH responsiveness by light. Overall, this study demonstrates optically gated uptake and release of functional amines in multi-responsive microgels and highlights their potential biological applications
Exploring the role of the electrically evoked Vestibulo-Ocular reflex in vestibular implant surgery
No full textPurposeVestibular implantation holds considerable potential as a therapeutic strategy for individuals with vestibular loss. A correct position of the stimulation electrodes is essential for effective implant functionality. For vestibular implants targeting the semi-circular canals, Vestibulo-Ocular Reflex testing (VOR testing) is used to evaluate functionality postoperatively. It might also be an effective tool for intraoperative decision making related to electrode placement. This study aimed to evaluate the predictive value of intraoperative VOR testing for the postoperative vestibular implant response. This would be the first step in exploring the usability of the VOR as intraoperative electrode placement indicator.MethodsNine patients with bilateral vestibulopathy were implanted with an investigational vestibulo-cochlear implant. Vestibulo-ocular reflexes (VOR) were electrically evoked using the implant, both intra- and postoperatively, and recorded using video-oculography. The correspondence between the intra- and postoperative measurements was evaluated. This included the presence of the VOR, activation threshold, eye velocity and alignment. Furthermore, the correlation between the intraoperative peak eye velocity and stimulation amplitude was assessed.ResultsIt was found that the presence of an intraoperative VOR has a high positive predictive value (1.0) for predicting the presence of a postoperative VOR. Additionally, the intraoperative VOR showed a high, though not perfect, negative predictive value (0.86) for predicting the absence of a postoperative VOR. The VOR activation threshold was higher, eye velocity was lower, and alignment differed on individual level, in the intra-operative measurements compared to the post-operative measurements. The intraoperative VOR peak eye velocity was related to stimulation amplitude.ConclusionIntraoperative VOR responses during vestibular implant surgery differ from postoperative responses, likely due to general anaesthesia. Despite this discrepancy, the presence of an intraoperative VOR is a strong predictor of postoperative VOR presence. Furthermore, intraoperative VOR eye velocity increases with higher stimulation amplitudes. These findings suggest that intraoperative VOR testing may aid in optimizing electrode placement during vestibular implant surgery
Clinical Applications of Corneal Cells Derived from Induced Pluripotent Stem Cells
No full textCorneal diseases are among the leading causes of blindness worldwide and the standard treatment is the transplantation of corneal donor tissue. Treatment for cornea-related visual impairment and blindness is, however, often constrained by the global shortage of suitable donor grafts. To alleviate the shortage of corneal donor tissue, new treatment options have been explored in the last decade. The discovery of induced pluripotent stem cells (iPSCs), which has revolutionized regenerative medicine, offers immense potential for corneal repair and regeneration. Using iPSCs can provide a renewable source for generating various corneal cell types, including corneal epithelial cells, stromal keratocytes, and corneal endothelial cells. To document the recent progress towards the clinical application of iPSC-derived corneal cells, this review summarizes the latest advancements in iPSC-derived corneal cell therapies, ranging from differentiation protocols and preclinical studies to the first clinical trials, and discusses the challenges for successful translation to the clinic
Magnetoelectric nanoparticle technology for mitigating motor deficits in Parkinsonian mice
No full textIntroduction: Deep brain stimulation (DBS) technology involves wired-in powering of electrodes to modulate deep brain targets in both clinical and preclinical settings. Previously, we demonstrated the feasibility of magnetoelectric nanoparticle (MENP)-based DBS for wireless modulation of the subthalamic nucleus (STh) in mice. However, key aspects such as their ability to alleviate symptoms in disease models, long-term stability and efficacy, as well as optimal magnetic field parameters used to power the particles, remain unaddressed. Material and method: Herein, for the first time, we applied MENP-based STh-DBS in a Parkinson's disease (PD) model induced by 6-hydroxydopamine (6-OHDA) lesioning to evaluate their potential to alleviate motor deficits. Throughout a parallel study, mice were monitored longitudinally for up to 18 months post injection to assess MENPs retention, efficacy, and long-term local effects. Results: MENP-based STh-DBS using a field of 140 Hz, 220 mT direct current (DC) and 8 mT of alternating current (AC) was able to improve the locomotion of 6-OHDA treated mice with over 95 % dopaminergic cell loss in the substantia nigra. Postmortem assessment revealed no evidence of sustained or enhanced astro- or microgliosis over 18 months, and no changes in MENP retention or performance. Conclusion: MENP-based STh-DBS can counteract behavioral disturbances caused by impaired neural circuits following extensive dopaminergic cell loss in PD mice. Additionally, no adverse effects or loss of efficacy were observed over time for up to 18 months with respect to astro- and microgliosis. While effective modulation was only achieved with a higher magnetic coil configuration, this finding represents a critical step toward refining MENP-based neuromodulation in PD
Sex and Treatment Outcomes of Atrial Fibrillation Ablation in End-Stage Heart Failure:Insights From CASTLE-HTx
No full textAssessing mesh size and diffusion of alginate bioinks:A crucial factor for successful bioprinting functional pancreatic islets
No full textThree-dimensional (3D) bioprinting has been utilised for the encapsulation of pancreatic islets for potentially treating type 1 diabetes. A crucial factor in selecting a cell compatible bioink, that maintains islet functionality, is the mesh size and diffusion capacity of the bioink. In this study, we present a screening strategy for alginate hydrogel formulations in three-dimensional bioprinting, utilizing the fluorescent recovery after photobleaching (FRAP) method and measuring the mesh size of the hydrogels. Subsequently, the 1.5 % alginate formulation that had been selected was used to bioprint the INS1E cell line, primary rat islets, or human islets. It was demonstrated that cell viability and functionality were maintained in all cell sources. This was evidenced by the observation that bioprinted pancreatic islets exhibited a response to physiological glucose levels. The present study indicates that both FRAP and hydrogel mesh size measurements are effective tools for predicting the diffusion of hormones through a hydrogel. These measures should therefore be incorporated into future screenings of hydrogel compositions for the 3D bioprinting of islets