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Abstract Automated quantification of brain tissues on MR images has greatly contributed to the diagnosis and follow-up of neurological pathologies across various life stages. However, existing solutions are specifically designed for certain age ranges, limiting their applicability in monitoring brain development from infancy to late adulthood. This retrospective study aims to develop and validate a brain segmentation model across pediatric and adult populations. First, we trained a deep learning model to segment tissues and brain structures using T1-weighted MR images from 390 patients (age range: 2–81 years) across four different datasets. Subsequently, the model was validated on a cohort of 280 patients from six distinct test datasets (age range: 4–90 years). In the initial experiment, the proposed deep learning-based pipeline, icobrain-dl, demonstrated segmentation accuracy comparable to both pediatric and adult-specific models across diverse age groups. Subsequently, we evaluated intra- and inter-scanner variability in measurements of various tissues and structures in both pediatric and adult populations computed by icobrain-dl. Results demonstrated significantly higher reproducibility compared to similar brain quantification tools, including childmetrix, FastSurfer, and the medical device icobrain v5.9 (p-value< 0.01). Finally, we explored the potential clinical applications of icobrain-dl measurements in diagnosing pediatric patients with Cerebral Visual Impairment and adult patients with Alzheimer’s Disease.

Introduction: Osteolytic spinal metastases (SM) have a higher risk of fracture. In this study we aim to confirm the remineralization of lytic SM after radiation therapy. Secondary the influence of SBRT compared to cEBRT and tumor type will be analyzed. Methods: A retrospective cohort study was performed. Results: 87 patients, 100 SM were included. 29 received SBRT, 71 cEBRT. Most common primary tumors were breast (35 %), lung (26 %) and renal (11 %). Both cEBRT and SBRT resulted in a significant increase of bone mineral density (BMD) (83.76 HU ± 5.72 → 241.41 HU ± 22.58 (p

Introduction Physical restraint (PR) is prescribed in patients receiving invasive mechanical ventilation in the intensive care unit (ICU) to avoid unplanned removal of medical devices. However, it is associated with an increased risk of delirium. We hypothesise that a restrictive use of PR, as compared with a systematic use, could reduce the duration of delirium in ICU patients receiving invasive mechanical ventilation.Methods and analysis The Restrictive use of Restraints and Delirium Duration in ICU (R2D2-ICU) study is a national multicentric, parallel-group, randomised (1:1) open-label, controlled, superiority trial, which will be conducted in 10 ICUs. A total of 422 adult patients requiring invasive mechanical ventilation for an expected duration of at least 48 hours and eligible for prescription of PR will be randomly allocated within 6 hours from intubation to either the restrictive PR use group or the systematic PR use group, until day 14, ICU discharge or death, whichever comes first. In both groups, PR will consist of the use of wrist straps. The primary endpoint will be delirium or coma-free days, defined as the number of days spent alive in the ICU without coma or delirium within the first 14 days after randomisation. Delirium will be assessed using the Confusion Assessment Method-ICU twice daily. Key secondary endpoints will encompass agitation episodes, opioid, propofol, benzodiazepine and antipsychotic drug exposure during the 14-day intervention period, along with a core outcome set of measures evaluated 90 days postrandomisation.Ethics and dissemination The R2D2-ICU study has been approved by the Comité de Protection des Personnes (CPP) ILE DE FRANCE III—PARIS (CPP19.09.06.37521) on June 10th, 2019). Participant recruitment started on 25 January 2021. Results will be published in international peer-reviewed medical journals and presented at conferences.Trial registration number NCT04273360.

Abstract Background Acute kidney injury (AKI) is frequent among critically ill patients. Renal replacement therapy (RRT) is often required to deal with severe complications of AKI. This technique is however associated with side effects such as hemodynamic instability and delayed renal recovery. In this study, we aimed to describe a novel model of hemodialysis in rats with AKI and depict a dialysis membrane performance. Methods Eighteen Sprague–Dawley rats received 0.75% adenine-rich diet to induce AKI. After 2 weeks, nine underwent an arterio-venous extracorporeal circulation (ECC) (ECC group) for 2 h without a dialysis membrane on the circuit and nine received a hemodialysis session (HD group) for 2 h with an ECC circuit. All rats were hemodynamically monitored, and glomerular filtration rate (GFR) was measured by transcutaneous fluorescence after the injection of FITC-Sinistrin. Blood samples were collected at different time points to assess serum creatinine and serum urea concentrations and to determine the Kt/V. Sinistrin concentration was also quantified in both plasma and dialysis effluent. Results After 2 weeks of adenine-rich diet, rats exhibited a decrease in GFR. Both serum urea and serum creatinine concentrations increased in the ECC group but remained stable in the HD group. We found no significant difference in serum creatinine and serum urea concentrations between groups. At the end of experiments, mean serum urea was 36.7 mmol/l (95%CI 19.7–46.9 mmol/l) and 23.6 mmol/l (95%CI 15.2–33.5 mmol/l) in the ECC and HD groups, respectively (p = 0.15), and mean serum creatinine concentration was 158.0 µmol/l (95%CI 108.1–191.9 µmol/l) and 114.0 µmol/l (95%CI 90.2–140.9 µmol/l) in the ECC and HD groups, respectively (p = 0.11). The Kt/V of the model was estimated at 0.23. Sinistrin quantity in the ultrafiltrate raised steadily during the dialysis session. After 2 h, the median quantity was 149.2 µg (95% CI 99.7–250.3 µg). Conclusions This hemodialysis model is an acceptable compromise between the requirement of hemodynamic tolerance which implies reducing extracorporeal blood volume (using a small dialyzer) and the demonstration that diffusion of molecules through the membrane is achieved.

Oncologic back pain, infection, inflammation, and trauma are the only specific etiologies of chronic low back pain (CLBP) in contrast to most patients who have non-specific CLBP. In oncologic patients developing CLBP, it is critically important to perform further investigation to exclude spinal metastases (SM).The incidence of cancer is increasing, with 15.7–30% developing SM. In the case of symptomatic SM, we can distinguish three main categories: tumor pain; mechanical pain due to instability, with or without pathologic fractures; and metastatic epidural spinal cord compression (MESCC) or radicular compression. Treatment of SM-related pain is dependent on these categories and consists of symptomatic treatment, target therapy to the bone, radiotherapy, systemic oncologic treatment, and surgery. The care for SM is a multidisciplinary concern, with rapid evolutions in all specialties involved. It is of primordial importance to incorporate the knowledge of specialists in all participating disciplines, such as oncology, radiotherapy, and spinal surgery, to determine the adequate treatment to preserve ambulatory function and quality of life while limiting the burden of treatment if possible. Awareness of potential SM is the first and most important step in the treatment of SM-related pain. Early diagnosis and timely treatment could prevent further deterioration. In this review, we explore the pathophysiology and symptomatology of SM and the treatment options for SM-related pain: tumor pain; mechanical pain due to instability, with or without pathologic fractures; and MESCC or radicular compression.

About half of patients with Graves' disease develop an orbitopathy related to an inflammatory expansion of the periorbital adipose tissue and muscles. We used a targeted metabolomic approach measuring 188 metabolites by mass spectrometry to compare the metabolic composition of tears in patients with active (n = 21) versus inactive (n = 24) thyroid-associated orbitopathy. Among the 44 metabolites accurately measured, 8 showed a significant alteration of their concentrations between the two groups. Two short-chain acylcarnitines, propionylcarnitine and butyrylcarnitine, and spermine showed increased concentrations in the tears of patients with active orbitopathy, whereas ornithine, glycine, serine, citrulline and histidine showed decreased concentrations in this group. In addition, the ratio putrescine/ornithine, representing the activity of ornithine decarboxylase, was significantly increased in patients with active compared to inactive orbitopathy (p = 0.0011, fold change 3.75). The specificity of this candidate biomarker was maintained when compared to a control group with unclassified dry eye disease. Our results suggest that the stimulation of ornithine decarboxylase by TSH receptor autoantibodies in orbital fibroblasts could lead to increased synthesis of spermine, through the increased activity of ornithine decarboxylase, that may contribute to periorbital expansion in Graves' ophthalmopathy.

This work investigates reactor model biases and their consequences in nuclear scenario simulations. Usually, the models for Pressurized Water Reactors are based on infinite 2D assembly depletion simulations, but recent work has shown the importance of 3D complete core simulation for uncertainty reduction. The consideration of a whole core leads to new reactor parameters in the simulations that may bring additional biases. The fuel temperature distribution is one of them, and previous work considered isothermal reactors, leading to probable uncertainties in spent fuel inventory at reactor discharge. To quantify those biases and their propagation in a full scenario simulation, new advanced reactor models have been developed, based on neutronics and thermal-hydraulics couplings at the core level performed with DONJON5. Results show that the plutonium isotopic quality of spent fuel is biased for an isothermal core, with values systematically higher than for multi-physics calculations. In order to propagate those discrepancies in fuel cycle simulations that involve plutonium recycling in PWR MOX fuels, the coupling between CLASS and DONJON was renewed in order to add new fuel parameters such as the fuel temperature in the core burn-up simulation. A new methodology for data interpolation from lattice calculation has been implemented that allows acceptable computational time for DONJON5 calculations that are done within the fuel cycle simulation performed by CLASS. Comparison between isothermal and multi-physics reactor models for advanced scenario simulations performed with CLASS shows that the isothermal hypothesis leads to biases up to 10% for plutonium inventory in the UOX spent fuel stockpile, comparable with biases associated with other reactor parameters such as the loading pattern.

Abstract Background The Biopsychosocial (BPS) model is recognized and widely accepted in the field of health care, particularly in rehabilitation. However, in clinical practice the applicability of the BPS model is a challenge for many professionals. Method This study aimed to explore the factors that impact the perception of rehabilitation professionals about the BPS model in Ukraine. In addition, the job satisfaction assessment was done to measure whether rehabilitation specialists in Ukraine fulfil their professional roles according to their expectations and values. Participants were 346 rehabilitation specialists from Ukraine who completed the Bio-Psycho-Social Scale (BPS) for Use in Healthcare and the Global Job Satisfaction Scale (GJSS). The ANOVA was used to investigate the outcome differences between the two scales. Results The highest proportion of responders in this study represented state health services. The BPS subscale outcomes on “assessment and reporting” and “professional knowledge and skills” were significantly higher for specialists from a private sector. The global job satisfaction scale outcomes did not differ between responders from the private and state health sector. The perception of professionals networks was associated with greater job satisfaction. Conclusions The findings suggest that conception of the BPS approach in rehabilitation system of Ukraine varies across the private and state settings. The professional network plays important role in job satisfaction of rehabilitation professionals in Ukraine. Future research focusing on education strategies to effectively train professionals to apply biopsychosocial approach to practice is of critical importance to prepare rehabilitation specialists in Ukraine.

The Wiskott–Aldrich syndrome (WAS) is an X-linked primary immune deficiency caused by a mutation in the WAS gene. This leads to altered or absent WAS protein (WASp) expression and function resulting in thrombocytopenia, eczema, recurrent infections, and autoimmunity. In T cells, WASp is required for immune synapse formation. Patients with WAS show reduced numbers of peripheral blood T lymphocytes and an altered T-cell receptor repertoire. In vitro, their peripheral T cells show decreased proliferation and cytokine production upon aCD3/aCD28 stimulation. It is unclear whether these T-cell defects are acquired during peripheral activation or are, in part, generated during thymic development. Here, we assessed the role of WASp during T-cell differentiation using artificial thymic organoid cultures and in the thymus of humanized mice. Although CRISPR/Cas9 WAS knockout hematopoietic stem and progenitor cells (HSPCs) rearranged the T-cell receptor and differentiated to T-cell receptor (TCR)+ CD4+ CD8+ double-positive (DP) cells similar to wild-type HSPCs, a partial defect in the generation of CD8 single-positive (SP) cells was observed, suggesting that WASp is involved in their positive selection. TCR repertoire analysis of the DP and CD8+ SP population, however, showed a polyclonal repertoire with no bias toward autoreactivity. To our knowledge, this is the first study of the role of WASp in human T-cell differentiation and on TCR repertoire generation.

Background and purpose: Spinal stereotactic ablative body radiotherapy (SABR) requires high precision. We evaluate the intrafraction motion during cone-beam computed tomography (CBCT) guided SABR with different immobilization techniques. Material and methods: Fifty-seven consecutive patients were treated for 62 spinal lesions with SABR with positioning corrected in six degrees of freedom. A surface monitoring system was used for patient set up and to ensure patient immobilization in 65% of patients. Intrafractional motion was defined as the difference between the last CBCT before the start of treatment and the first CT afterwards. Results: For all 194 fractions, the mean intrafractional motion was 0.1 cm (0–1.1 cm) in vertical direction, 0.1 cm (0–1.1 cm) in longitudinal direction and 0.1 cm (0–0.5 cm) in lateral direction. A mean pitch of 0.6° (0–4.3°), a roll of 0.5° (0–3.4°) and a rotational motion of 0.4° (0–3.9°) was observed. 95.5% of the translational errors and 95.4% of the rotational errors were within safety range. There was a significantly higher rotational motion for patients with arms along the body (p = 0.01) and without the use of the body mask (p = 0.05). For cervical locations a higher rotational motion was seen, although not significant (p = 0.1). The acquisition of an extra CBCT was correlated with a higher rotational (pitch) motion (p = 0

Background and purpose: Postoperative ultrahypofractionated radiation therapy (UHFRT) in 5 fractions (fx) for breast cancer patients is as effective and safe as conventionally hypofractionated RT (HFRT) in 15 fx, liberating time for higher-level daily online Image-Guided Radiation Therapy (IGRT) corrections. In this retrospective study, treatment uncertainties occurring in patients treated with 5fx (5fx-group) were evaluated using electronic portal imaging device (EPID)-based in-vivo dosimetry (EIVD) and compared with the results from patients treated with conventionally HFRT (15fx-group) to validate the new technique and to evaluate if the shorter treatment schedule could have a positive effect on the treatment uncertainties. Materials and methods: EPID-based integrated transit dose images were acquired for each treatment fraction in the 5fx-group (203 patients) and on the first 3 days of treatment and weekly thereafter in the 15fx-group (203 patients). A total of 1015 EIVD measurements in the 5fx-group and 1144 in the 15fx-group were acquired. Of the latter group, 755 had been treated with online IGRT correction (i.e., Online-IGRT 15fx-group). Results: In the 15fx-group 12.0% of fractions failed (FFs) compared to 3.8% in the 5fx-group and 6.9% in the online-IGRT 15fx-group. Causes for FFs in the 15fx-group compared with the 5fx-group were patient positioning (7.4% vs. 2.2%), technical issues (3.1% vs. 1.2%) and breast swelling (1.4% vs. 0.5%). In the online-IGRT 15fx-group, 2.5% were attributed to patient positioning, 3.8% to technical issues and 0.5% to breast swelling. Conclusions: EIVD demonstrated that UHFRT for breast cancer results in less FFs compared to standard HFRT. A large proportion of this decrease could be explained by using daily online IGRT.

Background: The purpose of this randomised study was to determine whether dose‐intensified stereotactic body radiotherapy (SBRT) for painful vertebral metastases results in increased rates of pain improvement compared with conventional external beam radiotherapy (cEBRT) (control) 6 months after treatment. Methods: This randomized, controlled phase 3 trial was conducted between November 2016 and January 2023, when it was stopped early. Patients were eligible if they were aged 18 years or older; had one or two painful, stable, or potentially unstable vertebral metastases; and had a life expectancy of 1 year or longer according to the investigator's estimates. Patients received 48.5 grays (Gy) in 10 fractions (with epidural involvement) or 40 Gy in five fractions (without epidural involvement) in the SBRT group and 30 Gy in 10 fractions or 20 Gy in five fractions in the cEBRT group, respectively. The primary end point was an improvement in the pain score at the treated site by at least 2 points (on a visual analog scale from 0 to 10 points) at 6‐month follow‐up. Data were analyzed on an intention‐to‐treat and per‐protocol basis. Results: Of 214 patients who were screened for eligibility, 63 were randomized 1:1 between SBRT (33 patients with 36 metastases) and cEBRT (30 patients with 31 metastases). The median age of all patients was 66 years, and 40 patients were men (63.5%). In the intention‐to‐treat analysis, the 6‐month proportion of patients who had metastases with pain reduction by 2 or more points was significantly higher in the SBRT group versus the control group (69.4% vs. 41.9%, respectively; two‐sided p =.02). Changes in opioid medication intake relative to baseline were nonsignificant between the groups. No differences were observed in vertebral compression fracture or adverse event rates between the groups. Conclusions: Dose‐intensified SBRT improved pain score more effectively than cEBRT at 6 months. In this randomized clinical trial that included 63 patients with 67 painful vertebral metastases, the proportion of those who had metastases with pain improvement at 6‐month follow‐up was 69% in the stereotactic body radiotherapy group versus 42% in the conventional external beam radiotherapy group: a significant difference. Changes in opioid medication intake relative to baseline between the groups were not significant, and dose‐intensified stereotactic body radiotherapy was not associated with increased risks of adverse events. [ABSTRACT FROM AUTHOR]

Oncologic back pain, infection, inflammation, and trauma are the only specific etiologies of chronic low back pain (CLBP) in contrast to most patients who have non-specific CLBP. In oncologic patients developing CLBP, it is critically important to perform further investigation to exclude spinal metastases (SM).The incidence of cancer is increasing, with 15.7–30% developing SM. In the case of symptomatic SM, we can distinguish three main categories: tumor pain; mechanical pain due to instability, with or without pathologic fractures; and metastatic epidural spinal cord compression (MESCC) or radicular compression. Treatment of SM-related pain is dependent on these categories and consists of symptomatic treatment, target therapy to the bone, radiotherapy, systemic oncologic treatment, and surgery. The care for SM is a multidisciplinary concern, with rapid evolutions in all specialties involved. It is of primordial importance to incorporate the knowledge of specialists in all participating disciplines, such as oncology, radiotherapy, and spinal surgery, to determine the adequate treatment to preserve ambulatory function and quality of life while limiting the burden of treatment if possible. Awareness of potential SM is the first and most important step in the treatment of SM-related pain. Early diagnosis and timely treatment could prevent further deterioration. In this review, we explore the pathophysiology and symptomatology of SM and the treatment options for SM-related pain: tumor pain; mechanical pain due to instability, with or without pathologic fractures; and MESCC or radicular compression. [ABSTRACT FROM AUTHOR]