Probability Of Outcome Research Articles

Influence of maximum diameter on fine-needle aspiration biopsy outcomes in ACR TI-RADS 5 thyroid nodules.

Fine needle aspiration (FNA) biopsy is a widely accepted method for diagnosing thyroid nodules. However, the influence of maximum diameter (MD) of ACR TIRADS 5 (TR5) thyroid nodules on the FNA outcomes remains debated. This study examined the influence of MD on the FNA outcomes and investigated the optimal MD threshold for FNA in TR5 nodules. We conducted a retrospective analysis of 280 TR5 thyroid nodules from 226 patients who underwent FNA from January to June 2022 in our department. Probably malignant (PM) group was defined as Bethesda V in cytopathology with confirmed BRAF V600E mutation or Bethesda VI, the other cytopathology outcomes were defined as probably benign (PB) group. We examined factors influencing malignant cytopathology outcomes and determined the optimal MD threshold for FNA in TR5 nodules using logistic regression and restricted cubic spline (RCS) analysis. Among these nodules, 58.2% (163/280) had PM outcomes. The PM group had a significantly larger MD than the PB group [6.5mm (range 5.0-8.4) vs. 5.3mm (range 4.0-7.0), p < 0.001]. In multivariate logistic regression fully adjusted for confounders, MD was significantly associated with PM outcomes [odds ratio 1.16, 95%CI 1.05-1.31; p = 0.042]. The highest quartile of MD had a greater likelihood of PM outcomes compared to the lowest quartile [odds ratio 4.71, 95% CI 1.97-11.69, p = 0.001]. The RCS analysis identified 6.2mm as the optimal MD threshold for FNA in TR5 nodules. MD significantly affects the probability of malignant outcomes in FNA of TR5 thyroid nodules. A MD threshold of ≥6.2mm is suggested for FNA in these nodules.

Ex vivo platform en route to functional precision medicine: clinical relevance in gynecological cancers.

A scientific interrogation-driven approach to the clinical management of cancer patients is based on molecular profiling of the tumor. Empowered by the knowledge of oncogenic drivers and biomarkers, oncologists chart an optimal treatment path toward increasing the mathematical probability of a positive outcome. In this entire chain of events, an experimental proof of logical interrogation has never been incorporated before. Here, we provide the first evidence that the result of ex vivo testing of a drug matched to the genomic profiling of an N-of-1 tumor can deliver meaningful insight connecting scientific interrogation and a clinical event. Using resected tissues from endometrial (EC) and ovarian (OC) cancer patients, we designed a personalized ex vivo platform to test combinations of drugs in the default histological architecture of the individual tumors. Following the CART-T cells' principle, we co-cultured with autologous T-cells to test targeted drugs and immune checkpoint inhibitors. The study was designed with a limited clinical information window from patient registration/consent to obtaining the tumor tissues, and adjuvant treatment/post-surgery event (PSE) data were accessed retrospectively. Using a checkerboard analysis, we found that PSE-free survival time was longer in patients whose therapy "matched" the effective drug combination in ex vivo culture/co-cultures compared to those with no effect. Specifically, out of 32 EC patients in the "test & treatment-matched" category whose tumor cells failed to respond to ex vivo drug testing, none achieved > 4 and > 3 years of PSE-free survival. In contrast, out of 38 EC patients in the "test & treatment-matched" category, 4 and 6 patients, whose tumor cells responded to drugs in ex vivo culture, achieved > 4 and > 3 years of PSE-free survival, respectively. Cases with genomically-guided ex vivo testing showed that a "match" between an effective ex vivo drug combination and therapy resulted in late PSE, whereas a "match" between prescribed treatment and an ineffective drug combination in ex vivo testing led to early PSE. Our study demonstrates that integrating genomic data with personalized drug testing on an ex vivo culture/co-culture platform is an effective tool for modeling functional precision medicine in gynecological cancers. This approach bridges the gap between next-generation drug testing in translational research and patient care, providing insight for improved treatment outcomes.

Artificial ventilation in patients with stroke: main results of the Russian multicenter observational clinical trial RETAS

To analyze the relationship between the characteristics of respiratory support (RS) for patients with stroke and clinical factors with the number and structure of complications, deaths, and length of stay in the intensive care unit (ICU) and duration of artificial pulmonary ventilation (ALV). The Russian multicenter observational clinical study «Respiratory Therapy for Acute Stroke» (RETAS) that enrolled 1289 patients with stroke requiring RS was conducted under the auspices of the All-Russian public organization «Federation of Anesthesiologists and Resuscitators». Indications for ALV, the use of hyperventilation, the maximum level of positive end-expiratory pressure, starting modes of mechanical ventilation, timing of tracheostomy, the incidence of protein-energy malnutrition (PEM) and infectious complications were analyzed. The following scales were used to assess the severity of the condition: the National Institutes of Health Stroke Severity Scale (NIHSS), the Glasgow Coma Scale, the Glasgow Outcome Scale (GOS). For the group of patients with a stroke severity of more than 20 NIHSS points, the mortality increase was associated with initial hypoxia (p=0.004), hyperventilation used to relieve intracranial hypertension (p=0.034), and starting ventilation with volume control (VC) compared with starting pressure-controlled ventilation (PC) (p<0.001). We found that the use of the instrumental monitoring of intracranial pressure was associated with a decrease in mortality (p<0.001). The absence of PEM in patients with stroke is associated with a higher probability of a positive outcome (GOS 4 and 5) for the group with NIHSS less than 14 points (p<0.001). Ventilator-associated tracheobronchitis and ventilator-associated pneumonia were associated with an increase in the duration of ALV, the duration of weaning from the ventilator (for ventilator-associated tracheobronchitis) and the duration of stay in the ICU, and also reduced the chances of favorable outcomes (p<0.05). The factors associated with increased mortality in acute stroke are: hypoxemia at the start of ALV, hyperventilation, starting ventilation with VC in comparison with starting ventilation with PC, the use of only clinical methods of monitoring intracranial pressure in comparison with instrumental monitoring. The adverse effect of PEM and infectious complications on the outcome in patients with acute stroke has been proven.

Who Gets the Kid? Female Empowerment and Child Custody in Taiwan

Women’s status in Taiwan has improved substantially due to rapid social and legal changes, yet how female empowerment affects child custody outcomes has been studied little. This study analyzes the entirety of divorce registration records in 2002–2004 and 2018–2020 to reveal the evolution of custodial arrangements in Taiwan. It pays particular attention to how mother’s changing traits and spousal pairings in age and education affect the probability of different child custody outcomes. The findings show that maternal age and education matter in both absolute and relative terms. Higher maternal age and education are associated with more mother-sole and joint custody decisions. Women in age and educational hypogamy secure mother-sole custody more often than their nonhypogamous peers. Furthermore, with improved women’s status at the society level, all women and particularly those in nontraditional unions now have become less likely to face a complete loss of child custody upon divorce than before.

The probable future of toxicology - probabilistic risk assessment.

Both because of the shortcomings of existing risk assessment methodologies, as well as newly available tools to predict hazard and risk with machine learning approaches, there has been an emerging emphasis on probabilistic risk assessment. Increasingly sophisticated AI models can be applied to a plethora of exposure and hazard data to obtain not only predictions for particular endpoints but also to estimate the uncertainty of the risk assessment outcome. This provides the basis for a shift from deterministic to more probabilistic approaches but comes at the cost of an increased complexity of the process as it requires more resources and human expertise. There are still challenges to overcome before a probabilistic paradigm is fully embraced by regulators. Based on an earlier white paper (Maertens et al., 2022), a workshop discussed the prospects, challenges and path forward for implementing such AI-based probabilistic hazard assessment. Moving forward, we will see the transition from categorized into probabilistic and dose-dependent hazard outcomes, the application of internal thresholds of toxicological concern for data-poor substances, the acknowledgement of user-friendly open-source software, a rise in the expertise of toxicologists required to understand and interpret artificial intelligence models, and the honest communication of uncertainty in risk assessment to the public.

Generating Task Reallocation Suggestions to Handle Contingencies in Human-Supervised Multi-Robot Missions

In a mission with significant uncertainty due to intermittent communications, delayed information flow, and robotic failures, the role of human supervisors is extremely challenging. As and when any new information arrives, humans must infer both the existing and predicted future states, identify potential contingencies, and update task assignments to robots rapidly. We propose methodologies for automated generation of task reallocation suggestions to humans to assist in the decision-making process. Our generated robot retasking plan minimizes a modified makespan of the mission, which incorporates task criticality and penalty for incomplete tasks. The plan considers the effects of potential mission contingencies on the tasks, the robots, and the future performance of the robots operating based on the previous task plans. Our method includes the incorporation of two optional tasks, i.e., relay and robot rescue, for performance improvement. The rescue task has probabilistic outcomes affecting the team size. One or more rescues are incorporated in a way that can minimize the expected value of the modified makespan overall possibilities of rescue outcomes. We have conducted performance evaluation using simulation, demonstrating the value of the optional tasks and performance enhancement using our method of incorporating them. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Note to Practitioners</i> —The work reported in this paper will be useful in applications where a team of agents is deployed to carry on a large-scale mission with communication constraints where the number of functional agents can change probabilistically. Typically, such uncertainty is encountered in applications that are challenging or dangerous in nature. Agents can have non-zero probabilities to fail while doing certain risky tasks and to get recovered by other agents. The proposed centralized multi-agent task reallocation method can help in proactively addressing potential contingencies in surveillance, search and rescue, or disaster relief to support resilient operations while having a supervisor in the higher chain of command.

Academic Solidarity and Placefulness: How Does Universitas Depend on Place?*

Abstract In this paper, I explore the foundational role of place in shaping academic solidarity, drawing from insights in educational research and phenomenology, particularly focusing on the concepts of Universitas and placefulness. I argue that academic solidarity is intricately tied to the experience of place, making it vulnerable to contemporary phenomena of displacement, exemplified by the proliferation of non-places and placelessness. These phenomena are predominantly driven by advancements in digitalization. Consequently, this leads to fragmentation within the academic community and atomization of learners, educators, and researchers, who increasingly operate as isolated entities instead of striving to form and cultivate a community of those who study. I argue that the most probable outcomes of progressing digitalization (an online platform and a digitally steered campus) do not provide a placeful environment for the practices of study and thus do not foster the growth of academic solidarity in a way a placeful institution of the University can.

Striking a Balance: Navigating Ethical Complexity in Healthcare: A reply to Mandal, Jharna; Ponnambath, Dinoop Korol; Parija, Subhash Chandra

Background: Medical ethics is a rational area of moral philosophy that addresses probable outcomes and disputes in duties and obligations. There are two schools of ethics that focus on decision-making: utilitarian and deontological. While in the utilitarian method, outcomes define the means and most benefit expected for the greatest number of people, in the deontological approach, outcomes/consequences may not only justify the means to attain them. In this paper we explore the idea of striking a balance proposed by Mandal J., et al (2016) between two very strong and conflicting ethical approaches (deontological &amp; utilitarian) viewpoints while making ethical decisions in the healthcare industry and focusing on real-world implementation challenges of these ethical approaches. We argue about the practical implication of “balance” as well as the limitations of “Dual processing theory of moral judgment”. Objectives: The objectives of this commentary are to critically analyze the concept of balance between utilitarian and deontological perspectives in ethical decision-making within healthcare and to highlight the challenges it poses in practical implementation. Conclusions: In conclusion, it is emphasized that striking a balance in healthcare ethics is important yet difficult, necessitating a dedication to compassion and honesty as well as a sophisticated grasp of ethical reasoning. In order to provide patient care that is both ethically sound and patient-centered, healthcare practitioners work to integrate utilitarian and deontological principles while taking into account a variety of contextual elements.

Probabilistic Outcomes Are Valued Less in Expectation, Even Conditional on Their Realization

Most theories of decision making under risk assume that payoffs and probabilities are separable. In the context of a lottery, the subjective value of a prospective outcome (the payoff) is assumed to be independent of the likelihood that the outcome will occur (the probability). In violation of this assumption, we present eight experiments showing that people anticipate less utility from uncertain outcomes than from certain outcomes, even conditional on their realization. The devaluation of uncertain outcomes is observed across different measures of utility (willingness to spend money or time; choice between different options), different populations (student and online samples), and different manipulations of uncertainty. We show that this result does not simply reflect a misunderstanding of the instructions or people’s aversion toward a “weird” transaction with unexplained features. We highlight the implications of this phenomenon for empirical investigations of risk preferences and conclude with a discussion of the psychological mechanisms that might drive the devaluation of probabilistic outcomes. This paper was accepted by Yuval Rottenstreich, behavioral economics and decision analysis. Supplemental Material: The data files are available at https://doi.org/10.1287/mnsc.2021.02284 .

Statistical similarity matching and filtering for clinical image retrieval by machine learning approach

Clinical image retrieval plays a pivotal role in modern healthcare for diagnostics and research, but prior research has grappled with the challenge of achieving high accuracy due to limited filtering techniques. The proposed method includes statistical distance measurements for similarity comparison and a machine learning technique for image filtering. Throughout this framework, the search area for similarity matching is reduced by first filtering away irrelevant images using the probabilistic outcomes of the Support Vector Machine (SVM) classification as class predictions of search and database images. Resizing is done as part of the preprocessing. Then, using Principal Component Analysis (PCA), the preprocessed data’s textural features, visual characteristics, and low-level features are extracted. The study also suggested an adaptive similarity matching method centered on a linear integration of feature-level similarities on the individual-level level. The precision and ranking order details of the most appropriate images retrieved and predicted by SVMs are considered when calculating the feature weights. The system continually alters weights for every distinctive search to generate beneficial outcomes. The supervised and unsupervised learning strategies are studied to link low-level global image features in the generated PCA-based Eigen Space using their high-level semantic and visual classifications to reduce the semantic gap and enhance retrieval effectiveness. The ground-truth database used in experiments has 1594 unique medical images with 3 different databases. Our method significantly improves the precision and recall rates in image retrieval tasks by combining sophisticated feature extraction, data-driven algorithms, and deep learning models. Research obtained an impressive accuracy of 0.99, demonstrating the effectiveness of our approach. This novel methodology addresses the limitations of prior research and provides a robust and reliable solution for clinicians and researchers in the medical field seeking to access and analyze relevant clinical images.

Predictors Associated With Prognosis of Patients on the Waiting List for Heart Transplantation.

Aim To identify predictors associated with the prognosis of patients on the heart transplant waiting list (HTWL) corresponding to UNOS class 2.Material and methods A HTWL database for 2010-2021 was retrospectively evaluated. The study included patients (n=162) who at the time of inclusion into the HTWL met UNOS class 2 and reached the endpoint of death, heart transplantation (HT), or exclusion from the HTWL due to an improvement of their condition. Mean age was 48±13 (from 11 to 67) years, 80% (n=130) were men, and body weight index was 24.9±4.4 kg/m2. Patients were divided into two groups: group 1 (n=131), patients who left the HTWL (improvement of CHF functional class) and patients who maintained the UNOS class 2 until HT; group 2 (n=31), patients who transferred from UNOS class 2 to UNOS class 1B/1A or died while on the HTWL.Results Patients of group 2 had lower systolic BP compared to patients of group 1 (100±17, mm Hg vs. 107±17 mm Hg, respectively, p=0.03). In group 1 compared to group 2, there was a higher proportion of patients with obesity, 29 (22%) vs. 1 (3%) (p=0.02). Laboratory blood tests: absolute lymphocyte count (2.0±0.7×109/L and 1.6±0.9×109/L, p=0.03), serum albumin (42±5 g/l and 40±6 g/l, p=0.03), red cell distribution width (RDW) (16±4% and 18±4%, p=0.01); sodium concentration (139±4 and 136±4 mmol/l, p=0.009). Patients from group 2 had a higher pulmonary vascular resistance (PVR) (4.0±2.4 Wood units vs. 3.2±1.4 Wood units, p=0.01) at baseline. A predictive model (p&lt;0.001) was developed to determine a probability of prognosis in HTWL. The model sensitivity was 75% and the specificity was 67%. High PVR was a predictor that worsened the prognosis in HTWL; higher serum concentrations of sodium and albumin increased the probability of a favorable outcome in HTWL.Conclusion During the period of waiting for HT, 19% of patients that met UNOS class 2 experienced deterioration of their condition (transitioned to UNOS 1) or died. The most important predictors for a better outcome in patients on HTWL who meet UNOS class 2 were higher serum levels of sodium and albumin and low pulmonary vascular resistance.

Risk of 30-Day All-Cause Readmission in Interstitial Lung Disease Patients after COVID-19: National-Level Data.

Rationale: Hospital readmission within 30 days poses challenges for healthcare providers, policymakers, and patients because of its impact on care quality, costs, and outcomes. Patients with interstitial lung disease (ILD) are particularly affected by readmission, which is associated with increased morbidity and mortality and reduced quality of life. Because small sample sizes have hindered previous studies, this study seeks to address this gap in knowledge by examining a large-scale dataset. Objective: To determine the rate and probability of 30-day all-cause readmission and secondary outcomes in patients with coronavirus disease (COVID-19) or ILD admitted to the hospital. Methods: This study is a nested cohort study that used the PearlDiver patient records database. Adult patients (age ⩾18 yr) who were admitted to hospitals in 28 states in the United States with COVID-19 or ILD diagnoses were included. We defined and analyzed two separate cohorts in this study. The first cohort consisted of patients with COVID-19 and was later divided into two groups with or without a history of ILD. The second cohort consisted of patients with ILD and was later divided into groups with COVID-19 or with a non-COVID-19 pneumonia diagnosis at admission. We also studied two other subcohorts of patients with and without idiopathic pulmonary fibrosis within the second cohort. Propensity score matching was employed to match confounders between groups. The Kaplan-Meier log rank test was applied to compare the probabilities of outcomes. Results: We assessed the data of 2,286,775 patients with COVID-19 and 118,892 patients with ILD. We found that patients with COVID-19 with preexisting ILD had an odds ratio of 1.6 for 30-day all-cause readmission. Similarly, an odds ratio of 2.42 in readmission rates was observed among hospitalized individuals with ILD who contracted COVID-19 compared with those who were hospitalized for non-COVID-19 pneumonia. Our study also found a significantly higher probability of intensive care admission among patients in both cohorts. Conclusions: Patients with ILD face heightened rates of hospital readmissions, particularly when ILD is combined with COVID-19, resulting in adverse outcomes such as decreased quality of life and increased healthcare expenses. It is imperative to prioritize preventive measures against COVID-19 and establish effective postdischarge care strategies for patients with ILD.

The guaranteed euros: Probabilistic discounting in behavioural-variant frontotemporal dementia.

Financial decision-making requires trading off between guaranteed and probabilistic outcomes and between immediate and delayed ones. While research has demonstrated that patients with behavioural-variant frontotemporal dementia (bvFTD) prefer immediate rewards at the expense of future ones (i.e. temporal discounting), little is known about how patients choose between smaller, guaranteed and larger, but probabilistic, outcomes (i.e. probabilistic discounting). We thus investigated probabilistic discounting by inviting 18 patients with bvFTD and 20 control participants to choose between fixed smaller monetary amounts and a fixed larger monetary amount with a variated probability of occurrence (e.g. 'Would you rather have 40€ for sure or a 20% chance of winning 100€?'). Results demonstrated lower scores, indicating higher risk tolerance, on the probabilistic discounting task in patients with bvFTD (while impulsively choosing more immediate rewards on the temporal discounting task) compared to control participants. Probabilistic discounting was significantly correlated with a decline in general cognitive performance in patients with bvFTD. When dealing between smaller, guaranteed, and larger, but probabilistic, rewards, patients with bvFTD tend to prefer guaranteed rewards and discount the uncertain ones.

The role of clinical and immunological parameters in predicting the effectiveness of additional immunotropic therapy in oxygen-dependent patients with COVID-19 coronavirus disease

Aim. The purpose of the research is to find out the role of clinical and immunological parameters in predicting the effectiveness of additional immunotropic therapy in oxygen-dependent patients with the coronavirus disease COVID-19. Material and methods. 79 oxygen-dependent patients with COVID-19 were examined, who received additional therapy with tocilizumab according to current protocols. The patients were divided into groups: I group – 39 patients who recovered; group II – 40 patients with a fatal outcome of the disease. The content of ferritin (Monobind Inc., USA), interleukin (IL) IL-2 (Elabscience, USA), IL-6 (Invitrogen, Austria), monocyte chemotactic protein-1 (MCP-1) (Elabscience, USA) was determined in the blood serum of patients and persons of the control group by the method of immunoenzymatic analysis. Statistical processing of the obtained data was carried out in the program Statistica 13 for Windows (StatSoft Inc., No. JPZ804I382130ARCN10-J). Results. Threshold levels of immunological parameters at different stages of observation, which have prognostic value regarding the risk of a fatal outcome of COVID-19, have been established. After 5 days of tocilizumab administration, the preservation of the indicator of the absolute number of blood lymphocytes ≤1.2 × 109/l (AUC = 0.631, p = 0.039), CRP level &gt;67.5 mg/l (AUC = 0.670, p = 0.020), IL-2 &gt;309.45 pg/ml (AUC = 0.761, p = 0.013), IL-6 &gt;4.66 pg/ml (AUC = 0.871, p &lt; 0.001) indicated a high probability of developing a fatal outcome of the disease in patients with COVID-19. The analysis of the diagnostic significance of ferritin showed the informativeness of the level of its increase as at the time of the start of observation &gt;548.02 ng/ml (AUC = 0.718, p = 0.004) and after 5 days the application of additional immunotropic therapy &gt;443.55 ng/ml (AUC = 0.736, p = 0.026). It has been proven that, in addition to immunological parameters, when assessing the probability of a fatal outcome of COVID-19, such clinical parameters as the presence of febrile fever at the time of the appearance of oxygen dependence (p &lt; 0.05) and the duration of oxygen dependence at the time of additional immunotropic therapy with tocilizumab are informative (p &lt; 0.05). Under the conditions of additional immunotropic therapy with tocilizumab more than 4 days after the onset of oxygen dependence, the probability of ineffectiveness of the specified additional treatment was significant (AUC = 0.756, p &lt; 0.001). Conclusions. The dynamics of immunological parameters in oxygen-dependent patients with COVID-19 during additional immunotropic therapy with tocilizumab has certain features with different treatment results. When predicting the probable risk of a fatal outcome of the disease, clinical parameters are informative, namely the appearance of febrile fever during the development of oxygen dependence and the duration of oxygen dependence until the moment of tocilizumab administration, and immunological parameters, namely the level of the absolute content of lymphocytes, ferritin, CRP, IL-2, IL-6 in the blood.

Adolescents and young adults are the most undiagnosed of HIV and virally unsuppressed in Eastern and Southern Africa: Pooled analyses from five population-based surveys.

Age and gender disparities within the HIV cascade of care are critical to focus interventions efficiently. We assessed gender-age groups at the highest probability of unfavorable outcomes in the HIV cascade in five HIV prevalent settings. We performed pooled data analyses from population-based surveys conducted in Kenya, South Africa, Malawi and Zimbabwe between 2012 and 2016. Individuals aged 15-59 years were eligible. Participants were tested for HIV and viral load was measured. The HIV cascade outcomes and the probability of being undiagnosed, untreated among those diagnosed, and virally unsuppressed (≥1,000 copies/mL) among those treated were assessed for several age-gender groups. Among 26,743 participants, 5,221 (19.5%) were HIV-positive (69.9% women, median age 36 years). Of them, 72.8% were previously diagnosed and 56.7% virally suppressed (88.5% among those treated). Among individuals 15-24 years, 51.5% were diagnosed vs 83.0% among 45-59 years, p<0.001. Among 15-24 years diagnosed, 60.6% were treated vs 86.5% among 45-59 years, p<0.001. Among 15-24 years treated, 77.9% were virally suppressed vs 92.0% among 45-59 years, p<0.001. Among all HIV-positive, viral suppression was 32.9% in 15-24 years, 47.9% in 25-34 years, 64.9% in 35-44 years, 70.6% in 45-59 years. Men were less diagnosed than women (65.2% vs 76.0%, p <0.001). Treatment among diagnosed and viral suppression among treated was not different by gender. Compared to women 45-59 years, young people had a higher probability of being undiagnosed (men 15-24 years OR: 37.9, women 15-24 years OR: 12.2), untreated (men 15-24 years OR:2.2, women 15-24 years OR: 5.7) and virally unsuppressed (men 15-24 years OR: 1.6, women 15-24 years OR: 6.6). In these five Eastern and Southern Africa settings, adolescents and young adults had the largest gaps in the HIV cascade. They were less diagnosed, treated, and virally suppressed, than older counterparts. Targeted preventive, testing and treating interventions should be scaled-up.

Outcome of endovascular stroke therapy in a large mandatory stroke-registry

BackgroundEndovascular stroke treatment (EST) has become the standard treatment for patients with stroke due to large vessel occlusion, especially in earlier time windows. Only few data from population-based registries on effectiveness of EST have been published.MethodsBaden–Wuerttemberg is the third largest state in Germany in terms of area and population and has a structured stroke concept since 1998 which includes mandatory collection of quality assurance data. In 2018 and 2019, 3820 of 39,168 ischemic stroke patients (9.8%) were treated by EST (age median 78 y, NIHSS median 14). We analyzed the clinical outcome of these patients determined with the modified Rankin Scale (mRS) at discharge from the hospital or with the initiation of palliative therapy using logistic regression analysis with adjustment for the mRS at admission, additive IVT, age, and NIHSS.ResultsThe probability of an excellent clinical outcome (mRS 0 or 1 at discharge) and for a good clinical outcome (mRS 0–2) were significantly higher in EST-patients (odds-ratio (OR) 1.27; 95% confidence interval (95% CI) 1.13–1.43, and OR of 1.15 (95% CI 1.04–1.28). Also, the regression model showed an advantage for EST-patients with less frequent ‘decision for palliative care’ (OR 0.87; 95% CI 0.78–0.98). Sensitivity analysis adjusting for intracranial vessel occlusion as further factor showed similar results.ConclusionOur data suggest that EST can be of benefit also for an area-wide unselected stroke population, in a large German federal state with sometimes long distance to the next thrombectomy center.

Prolonged venous hemodiafiltration and hemoperfusion with polymixin in fulminant meningococcal disease: A case report

Fulminate meningococcal infection is one of the most formidable life-threatening conditions in children, accompanied by a high probability of complications and adverse outcomes, including disability, irreversible damage to the central nervous system, and death. The key link in the pathogenesis of this condition is the massive release of endotoxins by the pathogen and total damage to the endothelium of all vessels, which underlies the development of septic shock and all complications. The use of extracorporeal hemocorrection methods is one of the most effective methods of treating fulminate meningococcal infection; however, despite the undoubted therapeutic effect, they are not included in the recommendations of a high level of evidence and are rarely used in routine clinical practice and, in most cases, only in the terminal phase of the disease. The study presented the characteristics of the course of generalized meningococcal infection in a 7-year-old child, including intensive care measures. Particular attention was paid to assessing the severity of the condition and the effectiveness of extracorporeal hemocorrection methods. The child’s condition upon admission to the intensive care unit was 11 points according to the pSOFA scale, which indicated the presence of decompensated multiorgan dysfunction and was the basis for prolonged venovenous hemodiafiltration. Based on the results of the endotoxin activity assay (0.67 units), hemoperfusion with polymyxin was conducted. During therapy, the patient’s condition stabilized. Sixty-eight hours after admission, medical support for hemodynamics was discontinued, and the parameters of invasive mechanical ventilation were reduced. On day 7 of treatment, the patient was extubated, and the events of respiratory distress did not increase over time. On day 8 after admission, with full compensation of all vital functions following ischemic damage and deep necrosis of the tissues of the lower extremities, the patient was transferred to a multidisciplinary surgical hospital for further treatment. Early informed use of extracorporeal hemocorrection techniques contributes to the rapid regression of septic shock events and recovery of the patient, demonstrating the high efficacy of the methods used and the need for further multicenter randomized trials to routinely use these therapies in clinical practice.

Predicting outcome in acute stroke with large vessel occlusion-application and validation of MR PREDICTS in the ESCAPE-NA1 population.

Predicting outcome after endovascular treatment for acute ischemic stroke is challenging. We aim to investigate differences between predicted and observed outcomes in patients with acute ischemic stroke treated with endovascular treatment and to evaluate the performance of a validated outcome prediction score. MR PREDICTS is an outcome prediction tool based on a logistic regression model designed to predict the treatment benefit of endovascular treatment based on the MR CLEAN and HERMES populations. ESCAPE-NA1 is a randomized trial of nerinetide vs. placebo in patients with acute stroke and large vessel occlusion. We applied MR PREDICTS to patients in the control arm of ESCAPE-NA1. Model performance was assessed by calculating its discriminative ability and calibration. Overall, 556/1105 patients (50.3%) in the ESCAPE-NA1-trial were randomized to the control arm, 435/556 (78.2%) were treated within 6 h of symptom onset. Good outcome (modified Rankin scale 0-2) at 3 months was achieved in 275/435 patients (63.2%), the predicted probability of good outcome was 52.5%. Baseline characteristics were similar in the study and model derivation cohort except for age (ESCAPE-NA1: mean: 70 y vs. HERMES: 66 y), hypertension (72% vs. 57%), and collaterals (good collaterals, 15% vs. 44%). Compared to HERMES we observed higher rates of successful reperfusion (TICI 2b-3, ESCAPE-NA1: 87% vs. HERMES: 71%) and faster times from symptom onset to reperfusion (median: 201 min vs. 286 min). Model performance was good, indicated by a c-statistic of 0.76 (95%confidence interval: 0.71-0.81). Outcome-prediction using models created from HERMES data, based on information available in the emergency department underestimated the actual outcome in patients with acute ischemic stroke and large vessel occlusion receiving endovascular treatment despite overall good model performance, which might be explained by differences in quality of and time to reperfusion. These findings underline the importance of timely and successful reperfusion for functional outcomes in acute stroke patients.

The domestication of SARS-CoV-2 into a seasonal infection by viral variants.

The COVID-19 pandemic was caused by the zoonotic betacoronavirus SARS-CoV-2. SARS-CoV-2 variants have emerged due to adaptation in humans, shifting SARS-CoV-2 towards an endemic seasonal virus. We have termed this process 'virus domestication'. We analyzed aggregate COVID-19 data from a publicly funded healthcare system in Canada from March 7, 2020 to November 21, 2022. We graphed surrogate calculations of COVID-19 disease severity and SARS-CoV-2 variant plaque sizes in tissue culture. Mutations in SARS-CoV-2 adapt the virus to better infect humans and evade the host immune response, resulting in the emergence of variants with altered pathogenicity. We observed a decrease in COVID-19 disease severity surrogates after the arrival of the Delta variant, coinciding with significantly smaller plaque sizes. Overall, we suggest that SARS-CoV-2 has become more infectious and less virulent through viral domestication. Our findings highlight the importance of SARS-CoV-2 vaccination and help inform public policy on the highest probability outcomes during viral pandemics.

Case report: role of multidisciplinary approach in a case of spine osteosarcoma with oligometastatic heart disease

Introduction. Primary spinal osteosarcoma and rare metastatic heart lesion are considered significant factors for poor prognosis. The available work indicates that combined treatment, including the radical surgery of heart solitary metastatic lesion, probably provides the best outcome.Case report. Man, 27-year-old, with Th8 spinal osteosarcoma and solitary left atrial metastasis. From October 2019 to February 2020 5 cycles of chemotherapy (high doses of platinum and doxorubicin) were carried out with positive effect. Next steps were surgery: March 2020 – spondylectomy of the Th8 vertebra with combined stabilization; September 2020 – subtotal resection with plasty of the right atrium, tricuspid valve and prosthesis of the right coronary artery. Between the first and second surgery, 4 more same chemotherapy cycles were carried out. Currently, 24 months after completion of treatment, there are no signs of the disease.Conclusion. The article presents a unique case of treatment of primary osteosarcoma and metastatic lesion of rare location. Multidisciplinary approach and combination treatment in specialized centers increase the probability of favorable outcome in such cases.