Early Course Research Articles

Early Time Courses of Recurrent Venous Thromboembolism and Bleeding during Apixaban or Dalteparin Therapy for Patients with Cancer.

In patients with acute venous thromboembolism (VTE), the rates of recurrence and major bleeding are highest during the first weeks of anticoagulation. The CARAVAGGIO trial demonstrated noninferiority of apixaban to dalteparin for treatment of cancer-associated VTE without an increased risk of major bleeding. We compared the early time course of VTE recurrence and major bleeding events of apixaban compared with dalteparin at 7, 30, and 90 days of treatment in patients with cancer-associated VTE. The study design of the CARAVAGGIO trial has been described. Eligible patients were randomly assigned to receive monotherapy with either apixaban or dalteparin for 6 months. The primary efficacy outcome was the incidence of objectively confirmed recurrent VTE. The primary safety outcome was major bleeding. In 1,155 patients, recurrent VTE after 7, 30, and 90 days occurred in 6 (1%), 15 (2.6%), and 27 (4.7%) patients in the apixaban arm versus 5 (0.9%), 20 (3.5%), and 36 (6.2%) patients respectively in the dalteparin arm. By day 7, 30, and 90, major bleeding events had occurred in 3 (0.5%), 9 (1.6%), and 16 (2.8%) patients in the apixaban group versus 5 (0.9%), 11 (1.9%), and 17 (2.9%) patients in the dalteparin group. The frequencies of recurrent VTE and major bleeding events at 7, 30, and 90 days of apixaban compared with dalteparin were similar in patients with cancer-associated VTE. This supports the use of apixaban for the initiation and early phase of anticoagulant therapy in cancer-associated VTE.

Enhancing Structural Engineering Education: Integrating Artificial Intelligence for Continuous Improvement

The study aims to analyze the impact of artificial intelligence (AI) usage on structural learning through student-developed programming in open-source software languages: Python, Octave, and OpenSees. The research collaborates with 90 undergraduate students in the early courses of civil engineering at the Universidad Nacional de Chimborazo. The ADDIE methodology is employed in the initial phase for planning, development, and monitoring. A survey on students' perceptions regarding effectiveness, satisfaction, recommendation, and feedback is conducted, followed by academic performance evaluation using a grading rubric to verify the achievement of set objectives. An analysis of factors contributing to AI-focused learning is then performed. Initial results revealed outliers, some deviating from study parameters and others discarded for a comprehensive view of study behavior. Regarding the survey data analysis, efficiency and satisfaction exhibited the highest reliability. Subsequently, variables were correlated considering their normality, showing a relationship between effectiveness and satisfaction; however, a strong connection cannot be guaranteed for these or other variables. Therefore, ANOVA tests, indicating positive linear relationships, and hypothesis testing were employed, demonstrating that students achieved objectives with a moderately high degree of effectiveness and satisfaction. The use of technological options and consideration of innovative learning methods can positively enhance the learning experience, contingent on prior education. Exploring artificial intelligence may prove challenging without guided information search based on predefined criteria and constraints.

The critical role of neutrophil-endothelial cell interactions in sepsis: new synergistic approaches employing organ-on-chip, omics, immune cell phenotyping and in silico modeling to identify new therapeutics.

Sepsis is a global health concern accounting for more than 1 in 5 deaths worldwide. Sepsis is now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis can develop from bacterial (gram negative or gram positive), fungal or viral (such as COVID) infections. However, therapeutics developed in animal models and traditional in vitro sepsis models have had little success in clinical trials, as these models have failed to fully replicate the underlying pathophysiology and heterogeneity of the disease. The current understanding is that the host response to sepsis is highly diverse among patients, and this heterogeneity impacts immune function and response to infection. Phenotyping immune function and classifying sepsis patients into specific endotypes is needed to develop a personalized treatment approach. Neutrophil-endothelium interactions play a critical role in sepsis progression, and increased neutrophil influx and endothelial barrier disruption have important roles in the early course of organ damage. Understanding the mechanism of neutrophil-endothelium interactions and how immune function impacts this interaction can help us better manage the disease and lead to the discovery of new diagnostic and prognosis tools for effective treatments. In this review, we will discuss the latest research exploring how in silico modeling of a synergistic combination of new organ-on-chip models incorporating human cells/tissue, omics analysis and clinical data from sepsis patients will allow us to identify relevant signaling pathways and characterize specific immune phenotypes in patients. Emerging technologies such as machine learning can then be leveraged to identify druggable therapeutic targets and relate them to immune phenotypes and underlying infectious agents. This synergistic approach can lead to the development of new therapeutics and the identification of FDA approved drugs that can be repurposed for the treatment of sepsis.

Early left ventricular microvascular dysfunction in diabetic pigs: a longitudinal quantitative myocardial perfusion CMR study

BackgroundMicrovascular pathology is one of the main characteristics of diabetic cardiomyopathy; however, the early longitudinal course of diabetic microvascular dysfunction remains uncertain. This study aimed to investigate the early dynamic changes in left ventricular (LV) microvascular function in diabetic pig model using the cardiac magnetic resonance (CMR)-derived quantitative perfusion technique.MethodsTwelve pigs with streptozotocin-induced diabetes mellitus (DM) were included in this study, and longitudinal CMR scanning was performed before and 2, 6, 10, and 16 months after diabetic modeling. CMR-derived semiquantitative parameters (upslope, maximal signal intensity, perfusion index, and myocardial perfusion reserve index [MPRI]) and fully quantitative perfusion parameters (myocardial blood flow [MBF] and myocardial perfusion reserve [MPR]) were analyzed to evaluate longitudinal changes in LV myocardial microvascular function. Pearson correlation was used to analyze the relationship between LV structure and function and myocardial perfusion function.ResultsWith the progression of DM duration, the upslope at rest showed a gradually increasing trend (P = 0.029); however, the upslope at stress and MBF did not change significantly (P > 0.05). Regarding perfusion reserve function, both MPRI and MPR showed a decreasing trend with the progression of disease duration (MPRI, P = 0.001; MPR, P = 0.042), with high consistency (r = 0.551, P < 0.001). Furthermore, LV MPR is moderately associated with LV longitudinal strain (r = − 0.353, P = 0.022), LV remodeling index (r = − 0.312, P = 0.033), fasting blood glucose (r = − 0.313, P = 0.043), and HbA1c (r = − 0.309, P = 0.046). Microscopically, pathological results showed that collagen volume fraction increased gradually, whereas no significant decrease in microvascular density was observed with the progression of DM duration.ConclusionsMyocardial microvascular reserve function decreased gradually in the early stage of DM, which is related to both structural (but not reduced microvascular density) and functional abnormalities of microvessels, and is associated with increased blood glucose, reduced LV deformation, and myocardial remodeling.

Co-Construction Online Learning Models in Early Childhood Education Management Courses

The challenge of online learning in higher education is that there is often a lack of focus on students taking part in lectures, which causes a loss of learning. This study aims to analyze the feasibility and effectiveness of the co-construction online learning model in early childhood education management courses. The research method uses a research and development approach with the ADDIE model. Data collection was carried out by interviews, questionnaires, and observations on 88 students taking early childhood education management courses. Product feasibility testing was carried out from questionnaire data analysis on 10 statement items using a four-rating scale, while observations and interviews were used to analyze the effectiveness of implementing the co-construction online learning model. Data analysis used qualitative descriptive and quantitative techniques to analyze the feasibility and effectiveness of implementing the co-construction online learning model. The results of the study in the electronic feasibility test for teaching materials achieved a score of 71.4%, which means it is feasible and does not need revision. While the effectiveness test was carried out twice with different timeframes, in the first data collection there were 73% of active students, then it increased in the second data collection with 88% of active students. This increase is to Skinner's theory of operant conditioning learning, where individual behavior is influenced by the repetition of actions received.

Mycosis Fungoides: The Great Masquerader – Trilogy Case Series

Mycosis fungoides, also known as granuloma fungoides or Alibert-Bazin syndrome, is the most common form of primary cutaneous T-cell lymphoma. In the early course of the disease, the skin lesions have significant overlap with many other primary cutaneous disorders like psoriasis, eczema, and tinea infections. Hence, early suspicion, prompt diagnosis by histopathological and immunohistochemical analysis, and regular follow-up are of utmost importance. Here we present a trilogy of cases of mycosis fungoides with varied skin lesions.

Obrasci neuropsihijatrijskih simptoma u primarnim i sekundarnim tauopatijama iz ugla negovatelja i pacijenata

Introduction/Aims: Understanding the differences in neuropsychiatric symptoms (NPSs) across tauopathies, particularly in the early stages of the disease, may aid in differential diagnosis. The aims of the research are as follows: a) to examine the patterns of NPSs in primary (frontotemporal dementia - FTD and progressive supranuclear palsy - PSP) and secondary (Alzheimer's disease - AD) tauopathies; b) to examine the differences in NPSs reported by patients and caregivers. Methods: The study included 312 patients, 176 of whom had a disease duration of ≤3 years. The presence of NPSs based on caregiver's report was assessed by neuropsychiatric questionnaire (NPI). Patient's assessment of NPSs was examined by Hamilton's Depression and Anxiety Scales and the Apathy Scale. Results: In AD, the most common and severe neuropsychiatric symptoms are mood disorders and apathy. In contrast, agitation-related symptoms are also prominent in FTD and PSP. The profile of NPSs in FTD and PSP is similar, but irritability and aberrant motor behavior are more pronounced in FTD, while sleep disturbances are dominant in PSP. The prevalence of NPSs reported by caregivers on NPI was higher than that reported by patients. Conclusions: FTD and PSP are characterized by more frequent and more severe NPSs and have distinct psychiatric patterns compared to AD, even in the early disease course. Caregiver's observations of the patient's behavior could be of key importance in distinguishing these tauopathies, particularly in the absence of hard motor and cognitive symptoms in early disease course. Assessments of depression, anxiety, and apathy by patients themselves and their caregivers differ significantly, and data from these two sources cannot be considered interchangeable and comparable.

A Comparative Analysis for GPA Prediction of Undergraduate Students Using Machine and Deep Learning

Recently the research field of machine learning has experienced a huge rise in popularity and growth. Machine Learning (ML) is a way of improving computational prediction models by allowing the computer to generate its own algorithm to predict outcomes, based on an existing dataset. In this paper, we demonstrate the application of Machine Learning to enhance the educational processes. We implemented regression and supervised learning techniques on data from King Saud University, Riyadh, Saudi Arabia, to construct a predictive model for student performance. This allows for timely interventions in students' academic paths. We utilized extensive and diverse course records, encompassing several academic years and programs, to conduct a comparative analysis of various Machine and Deep Learning methodologies, assessing their efficacy through performance metrics. The developed ML/DL algorithms use Grade Point Averages (GPAs) of courses and semesters as explanatory features to predict the student’s final GPA, which is the target value of the models. Based on the results, the linear and bagging regression models have the best Mean Absolute Error (MAE) performance metric. To ensure there will be enough time for academic intervention, data of early courses and semesters are used.

An Effective Therapy of Acute Necrotizing Encephalopathy of Childhood: a Case Report

Acute necrotizing encephalopathy of childhood is a rare type of encephalopathy characterized by multiple bilateral brain lesions, mainly involving the thalami but also the putamina, internal and external capsules, cerebellar white matter, and the brainstem tegmentum. It is a rare condition; the first case was described in 1995, and many cases have been reported in Asia and in many Western countries. Most cases are sporadic; however, a few cases of recurrent and/or familial episodes have been reported, secondary to mutations in the RANBP2 gene) and other gene mutations that are all responsible of normal mitochondrial functions. Clinically, it is characterized by acute encephalopathy with dramatic neurological deficits/symptoms. The condition usually has a poor prognosis with high morbidity and mortality rates. We report a 5-year-old boy who showed a typical presentation of this rare condition after obtaining the consent of his legal guardians. We demonstrate how the effective combination of immune suppressive therapy with the mitochondrial cocktail during the early course of the disease leads to clinical and radiological improvement.

Meta-analysis of laparoscopic versus open D2 gastrectomy in managing locally advanced gastric cancer: early postoperative course and pathological outcomes

Background With a fifth incidence and a third death rate among all malignancies, stomach cancer is a serious worldwide health problem. The best course of treatment is removing all lymph nodes together with the tumor, increasing the likelihood of survival. Laparoscopic gastrectomy has become more common because of its advantages in terms of appearance, decreased discomfort, and shorter hospital stays; this is especially true in Korea and Japan. For locally advanced gastric cancer, it is still unclear if laparoscopic D2 gastrectomy is more feasible and effective than open surgery. Patients and methods This study conducted a systematic review and meta-analysis to evaluate the differences between laparoscopic and open D2 gastrectomy in terms of feasibility, radicality, surgical outcomes, and postoperative complications. PRISMA statement guidelines and Cochrane handbook for Systematic Reviews of Interventions were followed. Relevant databases were searched, and studies published between 2017 and September 2022 were included. Key outcome measures included operative time, blood loss, postoperative recovery, pathological outcomes, and lymph node involvement. Results The meta-analysis included a total of 22 studies. The operative time was significantly shorter for laparoscopic D2 gastrectomy compared with open surgery. However, laparoscopic D2 gastrectomy was associated with higher blood loss. Postoperative recovery measures, such as the time to first flatus and first oral intake, were significantly shorter for laparoscopic D2 gastrectomy. Pathological outcomes showed no significant differences in terms of resection margins and tumor size. The number of harvested lymph nodes did not significantly differ between laparoscopic and open D2 gastrectomy. Laparoscopic D2 gastrectomy demonstrated a lower rate of positive lymph nodes compared with open surgery. Conclusion Based on the findings of this meta-analysis, laparoscopic D2 gastrectomy seems to be a safe and practical procedure for treating patients with locally advanced gastric cancer. It is associated with reduced blood loss, faster postoperative recovery, equivalent postoperative complications, and comparable oncological safety. These results support the use of laparoscopic D2 gastrectomy as an effective alternative to open surgery in the management of advanced gastric cancer.

누리과정 교사용 지도서 내용 분석: 신체활동과 영양교육을 중심으로

This study aimed to examine the content categories related to physical activity and nutrition education by area and analyze how much related activities are included in the early Nuri course at the national level related to physical health of young children, focusing on the Nuri course commentary by age and the teacher's guide. In order to analyze the contents and activities related to physical health in the Nuri course, the subjects of the study were the Nuri course commentary and the Nuri course teacher's guide distributed by the Ministry of Education, Science and Technology and the Ministry of Health and Welfare in 2013, and the frequency was calculated. As a result of the study, content related to physical activity was included in the physical exercise/health area and the art experience area, and the content categories directly related to physical activity and exercise were ‘body recognition’, ‘body control and basic exercise’, and ‘body control’. ‘Participating in activities’ and ‘Expressing through movement and dance’ among ‘Artistic expression’ in the field of art experience. In addition, the contents of nutrition education were covered in the physical exercise and health area, and it was related to ‘healthy living’ content category. Second, there were a total of 101 activities dealing with physical activity in the 5-year-old Nuri course, 147 activities in the 4-year-old and 120 activities in the 3-year-old, and the most physical activity-related activities were covered in the 4-year-old course. As for nutrition education activities, 24 activities were presented for 3 years old, 29 for 4 years old, and 22 activities for 5 years old. This study is significant in that it provided basic data on what parts are lacking and need to be improved to improve the physical health of young children when revising the national level curriculum for young children.

Post-laparoscopic cholecystectomy pancreatitis

Laparoscopic cholecystectomy is one of the commonest operations performed on the biliary system. Acute pancreatitis following Lap-chole is quite uncommon. Whether pancreatitis is a complication or a sequalae to surgical treatment of gall stone disease continues to be a debatable issue. A 37-year-old lady underwent laparoscopic cholecystectomy for incidentally diagnosed gall stones. Early post-operative course was uneventful. The patient presented 3 weeks after surgery with severe excruciating abdominal pain and was diagnosed as acute pancreatitis by ultrasound evaluation. Liver function tests were altered with raised bilirubin, serum lipase and amylase. MRCP revealed a normal biliary tract. Pancreas showed changes of acute interstitial pancreatitis. Patient responded to conservative line of treatment. Acute pancreatitis could be a known complication following laparoscopic cholecystectomy. What causes pancreatitis continues to be a matter for debate. MRCP is the investigation of choice. Interventional endoscopy (ERCP) is indicated in cases of impacted gallstone in the CBD. While if the CBD is clear of stones, aggressive conservative management will suffice.

Education on Rural Construction Issues in Lithuania, 1918–1940

In this article the education of farmers and craftsmen about the construction of modern farmsteads during interwar period is assessed. Information on the subject was collected from interwar press and archival documents. The main features of modern interwar farmsteads are rational structuring, compliance with hygiene requirements, comfortability and aestheticism. These ideas were propagated by state institutions, although up to the 3rd decade it was not fully established. When the administration of rural construction matters was commissioned to the Žemės ūkio rūmai, the most important works in this direction were carried out. The Construction Department was established in 1929, and the construction technicians who worked there were the key players in the promotion of the conceptual framework. Therefore, their proper training and the provision of the necessary number of specialists was an essential prerequisite for the purposeful education of farmers and building tradesmen.&#x0D; Organising education for farmers one of the main goals was to achieve the largest possible number of persons and thus promote the importance of the implementation of the ideas of modernization of rural construction. Therefore, for this, the periodical press, educational publications, short-term courses and lectures on the issues of improving rural construction and the management of homesteads, as well as exhibitions where construction technologies were demonstrated and specialist advice was provided, were actively used for this. Given the gradual increase in farmers’ interest in the ideas promoted, as well as their active participation in the educational programmes, there is no doubt that the measures chosen were quite successful.&#x0D; Rural craftsmen also played an equally important role in the modernisation campaign. Therefore, since the end of the 1930s, short courses have been organised annually to raise their qualifications. The scope of these works was rising, although it affected only part of craftsmen and did not solve the lack of qualified specialists. In the 4th decade, the new laws and rules of rural building regulation were implemented. Also, the necessity for higher number of qualified construction craftsmen that would be able to implement modern building principles was realized. This resulted in first specialized craft schools for carpenters, masons and furnace workers. It was thought that these schools together with earlier courses had to form construction craftsmen education system. Although work in this direction was halted shortly afterwards, the establishment of the specialised schools was an indication of the prioritisation of construction issues and thus of the implementation of modernisation principles.

The potential role of extracorporeal cytokine removal with CytoSorb® as an adjuvant therapy in Acute Respiratory Distress Syndrome.

Management of acute respiratory distress syndrome (ARDS) represents one of the greatest challenges in intensive care and despite all efforts mortality remains high. One common phenotype of ARDS is that of a secondary injury to a dysregulated inflammatory host response resulting in increased capillary congestion, interstitial lung edema, atelectasis, pulmonary embolism, muscle wasting, recurring infectious episodes, and multiple organ failure. In cases of hyperinflammation, immunomodulation by extracorporeal cytokine removal such as the CytoSorb hemoadsorption cartridge could conceptually enhance lung recovery during the early course of the disease. The aim of this narrative review is to summarize the currently available data in this field and to provide an overview of pathophysiology and rationale for the use of CytoSorb hemoadsorption in patients with hyperinflammatory ARDS.

Endoscopic Ultrasound-Guided Celiac Plexus Block Can Be a Useful Procedure for Pain Relief in Chronic Pancreatitis When Used Selectively

Abstract Background and Objectives: Endoscopic ultrasound (EUS)-guided celiac plexus block (CPB) for pain relief in chronic pancreatitis (CP) has wide variation in results as reported in the literature. The objective was to find out the efficacy of EUS-CPB in painful CP from our region where phenotype of CP is different from West and to find out factors favoring response to EUS-CPB. Methods and Results: Patients with known CP who underwent EUS-CPB were assessed for response to CPB. Response to EUS-CPB was recorded as more than 50% reduction in visual analogue scale (VAS) score for pain severity at 1 week, 4 weeks, 12 weeks and 24 weeks after procedure. Factors between responders and nonresponders were analyzed. Among 29 patients who underwent EUS-CPB during the study period, response was seen in 72.4% patients after the procedure. The mean time to response to EUS-CPB was 1.22 (± 0.43) days. Mean duration of response was 8 months (± 4.73). Short duration of painful CP (≤2 years) was seen in 15 patients (51.72%) and long duration (&gt;2 years) was seen in 14 (48.27%). Among responders (21/29), those patients who had short duration of disease had significantly lower median VAS score at 12 weeks, (1 versus 3, p-value= 0.026) and at 24 weeks, (1.5 versus 2.5, p-value= 0.049), as compared to those with longer duration of disease. Overall, 83.3% males responded as compared to 54.54% females (p = 0.04). Significant proportion of subjects who responded either stopped or used analgesics occasionally (p &lt; 0.0001). There was no statistically significant difference in response to EUS-CPB with respect to age, prior history of endoscopic retrograde cholangiopancreatography (ERCP), etiology of CP, prior history of surgery, or whether only EUS-CBP was done (p &gt; 0.05 for all). Conclusion: EUS-CPB can be effective when used in select group of painful CP patient who are not immediate candidates for surgery especially in early course of disease. It can be offered to patients with persistent pain despite optimum medical therapy. When effective, it can reduce need for analgesic medication at least in short to medium term.

A journey through course development

This paper discusses the design process in the development of an undergraduate early childhood course. This design process was grounded in learning theory, using a team-based collaborative process to consider, develop and refine the course design. It started with a reflection on the learners and the learning environment. It then moved into an iterative process of investigation, creation and refinement of a new course that addresses the characteristics of the learners, the learning environment, authentic assessment and the learning outcomes holistically. This paper details the design process from initial conceptual thinking through to the final proposal ready for the University governance process and accreditation approval. Future directions could consider investigating the experience of all stakeholders involved in the process, as well as the student experience of the new course, to inform the process of collaborative course design.

Pathologic approach to Neonatal cholestasis with a simple scoring system for biliary atresia

A liver biopsy is essential for the diagnostic workup of persistent neonatal cholestasis (NC). The differential diagnosis of NC is broad, including obstructive and non-obstructive causes. In addition, histologic features of certain disorders may be non-specific in the early course of the disease. To evaluate liver biopsies using a practical histopathologic approach for NC and to define a simple scoring system for biliary atresia (BA) for routine clinical practice. From June 2006 to December 2021, liver biopsy specimens from infants with persistent NC were examined by two independent pathologists. The cases diagnosed as BA were correlated with clinical, radiologic, and laboratory data to calculate the final score. Four hundred and fifty-nine cases were enrolled in the study. They had a mean age of 63.94 ± 20.62 days and were followed for a median time of 58 (1–191) months. They included 162 (35.3%) cases of BA. On multivariate analysis, portal edema, ductular proliferation, cholangiolitis, and bile duct/ductular plugs were the histopathologic predictors of BA. A liver biopsy did perform well with a 95.1% sensitivity, 91.6% specificity, 86% PPV, and 97.1% NPV. At a cutoff of 5 of the scoring system, diagnosis of BA could be done with a sensitivity of 95.1% and a specificity of 100%. We have shown detailed histopathologic features of BA with more depth to infants aged ≤ 6 weeks. We have developed a simple scoring system using a combination of liver biopsy with non-invasive methods to increase the diagnostic accuracy of BA.

Temporary employment and wage inequality over the life course

Abstract Wage inequality between workers with different levels of educational attainment has been shown to increase over the life course. In this study, we investigate to what extent this growth is explained by temporary employment. Using linked employer-employee register data from the Netherlands, we follow the labour market careers of workers born in 1979. We decompose the impact of temporary employment on the change in the wage gap over the life course into two distinct components: (i) changes in group-specific temporary employment rates (risk) and (ii) changes in group-specific effects of temporary employment on wages (vulnerability). In line with previous research, we find a marked growth of the educational wage gap over the life course in the Netherlands. While group differences in temporary employment risk changed throughout the observation period to the detriment of less-educated workers, group differences in vulnerability to temporary employment diverged specifically during the early life course. Overall, temporary employment explains around 9 per cent of the change in the wage gap between workers with different levels of educational attainment by the age of 38 relative to age 28.

The Association Between Tobacco Use and Risk of COVID-19 Infection and Clinical Outcomes in Sweden: A Population-Based Study

Background: The association between tobacco use and COVID-19 is controversial. During the early course of the pandemic, limited testing prevented studying a wide spectrum of clinical manifestations.Objective: To examine the potential causal association between tobacco use and COVID-19 during the second wave (1 October 2020–30 June 2021) of the pandemic in Stockholm, Sweden.Methods: A population-based cohort study was conducted in the Stockholm region of Sweden, with information on tobacco use collected prior to the pandemic. Adjusted relative risks (RR) of COVID-19 and 95% confidence intervals (CI) were calculated, contrasting current smokers and snus users to non-users of tobacco.Results: Compared with non-users of tobacco, current smokers had a lower risk of COVID-19 (RR 0.78, 95% CI = 0.75–0.81) and of hospitalisation for the disease. Current snus users had a higher risk of COVID-19. Heavy smokers and snus users had longer hospital stays than non-users of tobacco.Conclusion: Tobacco use may have a different impact on the risk of being infected with SARS-CoV-2 and the risk of developing severe clinical manifestations. Further research is needed to determine the underlying mechanisms.

Prolonged course of brain edema and neurological recovery in a translational model of decompressive craniectomy after closed head injury in mice.

The use of decompressive craniectomy in traumatic brain injury (TBI) remains a matter of debate. According to the DECRA trial, craniectomy may have a negative impact on functional outcome, while the RescueICP trial revealed a positive effect of surgical decompression, which is evolving over time. This ambivalence of craniectomy has not been studied extensively in controlled laboratory experiments. The goal of the current study was to investigate the prolonged effects of decompressive craniectomy (both positive and negative) in an animal model. Male mice were assigned to the following groups: sham, decompressive craniectomy, TBI and TBI followed by craniectomy. The analysis of functional outcome was performed at time points 3d, 7d, 14d and 28d post trauma according to the Neurological Severity Score and Beam Balance Score. At the same time points, magnetic resonance imaging was performed, and brain edema was analyzed. Animals subjected to both trauma and craniectomy presented the exacerbation of the neurological impairment that was apparent mostly in the early course (up to 7d) after injury. Decompressive craniectomy also caused a significant increase in brain edema volume (initially cytotoxic with a secondary shift to vasogenic edema and gliosis). Notably, delayed edema plus gliosis appeared also after decompression even without preceding trauma. In prolonged outcomes, craniectomy applied after closed head injury in mice aggravates posttraumatic brain edema, leading to additional functional impairment. This effect is, however, transient. Treatment options that reduce brain swelling after decompression may accelerate neurological recovery and should be explored in future experiments.