Background
Deep‐learning is widely used for lesion classification. However, in the clinic patient data often has missing images.
Purpose
To evaluate the use of generated, duplicate and empty(black) ...images for replacing missing MRI data in AI brain tumor classification tasks.
Study Type
Retrospective.
Population
224 patients (local‐dataset; low‐grade‐glioma (LGG) = 37, high‐grade‐glioma (HGG) = 187) and 335 patients (public‐dataset (BraTS); LGG = 76, HGG = 259). The local‐dataset was divided into training (64), validation (16), and internal‐test‐data (20), while the public‐dataset was an independent test‐set.
Field Strength/Sequence
T1WI, T1WI+C, T2WI, and FLAIR images (1.5T/3.0T‐MR), obtained from different suppliers.
Assessment
Three image‐to‐image translation generative‐adversarial‐network (Pix2Pix‐GAN) models were trained on the local‐dataset, to generate T1WI, T2WI, and FLAIR images. The rating‐and‐preference‐judgment assessment was performed by three human‐readers (radiologist (MD) and two MRI‐technicians). Resnet152 was used for classification, and inference was performed on both datasets, with baseline input, and with missing data replaced by 1) generated images; 2) duplication of existing images; and 3) black images.
Statistical Tests
The similarity between the generated and the original images was evaluated using the peak‐signal‐to‐noise‐ratio (PSNR) and the structural‐similarity‐index‐measure (SSIM). Classification results were evaluated using accuracy, F1‐score and the Kolmogorov–Smirnov test and distance.
Results
For baseline‐state, the classification model reached to accuracy = 0.93,0.82 on the local and public‐datasets. For the missing‐data methods, high similarity was obtained between the generated and the original images with mean PSNR = 35.65,32.94 and SSIM = 0.87,0.91 on the local and public‐datasets; 39% of the generated‐images were labeled as real images by the human‐readers. The classification model using generated‐images to replace missing images produced the highest results with mean accuracy = 0.91,0.82 compared to 0.85,0.79 for duplicated and 0.77,0.68 for use of black images;
Data Conclusion
The feasibility for inference classification model on an MRI dataset with missing images using the Pix2pix‐GAN generated images, was shown. The stability and generalization ability of the model was demonstrated by producing consistent results on two independent datasets.
Level of Evidence
3
Technical Efficacy
Stage 5
Purpose: White-matter tract segmentation in patients with brain pathology can guide surgical planning and can be used for tissue integrity assessment. Recently, TractSeg was proposed for automatic ...tract segmentation in healthy subjects. The aim of this study was to assess the use of TractSeg for corticospinal-tract (CST) segmentation in a large cohort of patients with brain pathology and to evaluate its consistency in repeated measurements. Methods: A total of 649 diffusion-tensor-imaging scans were included, of them: 625 patients and 24 scans from 12 healthy controls (scanned twice for consistency assessment). Manual CST labeling was performed in all cases, and by 2 raters for the healthy subjects. Segmentation results were evaluated based on the Dice score. In order to evaluate consistency in repeated measurements, volume, Fractional Anisotropy (FA), and Mean Diffusivity (MD) values were extracted and correlated for the manual versus automatic methods. Results: For the automatic CST segmentation Dice scores of 0.63 and 0.64 for the training and testing datasets were obtained. Higher consistency between measurements was detected for the automatic segmentation, with between measurements correlations of volume = 0.92/0.65, MD = 0.94/0.75 for the automatic versus manual segmentation. Conclusions: The TractSeg method enables automatic CST segmentation in patients with brain pathology. Superior measurements consistency was detected for the automatic in comparison to manual fiber segmentation, which indicates an advantage when using this method for clinical and longitudinal studies.
Abstract
Context
Daily growth hormone (GH) injections can be burdensome for patients and carers. Somapacitan is a long-acting, reversible albumin-binding GH derivative in development for once-weekly ...administration in patients with growth hormone deficiency (GHD).
Objective
The objective of this study is to evaluate the efficacy, safety, and tolerability of once-weekly somapacitan vs once-daily GH.
Design
REAL 3 is a multicenter, randomized, controlled, double-blind (somapacitan doses), phase 2 study with a 26-week main and 26-week extension phase (NCT02616562).
Setting
This study took place at 29 sites in 11 countries.
Patients
Fifty-nine GH treatment-naive prepubertal children with GHD were randomly assigned; 58 completed the trial.
Interventions
Interventions comprised 3 somapacitan doses (0.04 n = 16, 0.08 n = 15, or 0.16 mg/kg/wk n = 14) and daily GH (0.034 mg/kg/d n = 14), administered subcutaneously.
Main Outcome Measures
The primary end point was height velocity (HV) at week 26. Secondary efficacy end points included HV SD score (SDS) and insulin-like growth factor-I (IGF-I) SDS.
Results
At week 26, mean (SD) annualized HV for the somapacitan groups was 8.0 (2.0), 10.9 (1.9), and 12.9 (3.5) cm/year, respectively, vs 11.4 (3.3) cm/year for daily GH; estimated treatment difference (somapacitan 0.16 mg/kg/week—daily GH): 1.7 95% CI –0.2 to 3.6 cm/year. HV was sustained at week 52, and significantly greater with somapacitan 0.16 mg/kg/week vs daily GH. Mean (SD) change from baseline in HV SDS at week 52 was 4.72 (2.79), 6.14 (3.36), and 8.60 (3.15) for the somapacitan groups, respectively, vs 7.41 (4.08) for daily GH. Model-derived mean (SD) IGF-I SDS for the somapacitan groups was −1.62 (0.86), −1.09 (0.78), and 0.31 (1.06), respectively, vs −0.40 (1.50) observed for daily GH. Safety and tolerability were consistent with the profile of daily GH.
Conclusions
In children with GHD, once-weekly somapacitan 0.16 mg/kg/week provided the closest efficacy match with similar safety and tolerability to daily GH after 26 and 52 weeks of treatment. A short visual summary of our work is available (1).
Summary
Carfilzomib has been established in previous years as a treatment for patients with relapsed and/or refractory multiple myeloma (RR‐MM). A retrospective multicentre study to evaluate the ...clinical use of carfilzomib for RR‐MM outside of a clinical trial setting was conducted by our group. One hundred and thirty‐five patients were included. All patients had been previously exposed to bortezomib and 93% had also been treated with lenalidomide. The vast majority of patients received carfilzomib as part of a two‐ or three‐drug combination. The overall response rate was 47·2%. Multivariate analysis revealed bortezomib resistance, lenalidomide resistance and albumin <35 g/l to negatively impact the likelihood of achieving response. The median duration of response was 8·4 months, and was significantly higher in patients receiving three‐drug combination and patients presenting without extramedullary disease. The median progression‐free survival and overall survival for the entire cohort was 4·9 months (95% confidence interval CI 3·8–6·4) and 12·2 months (95% CI 9‐not reached), respectively. Toxicity was manageable, although treatment‐related death was seen in 5% of patients. In the setting of progressive multiple myeloma, carfilzomib in a combination regimens yields effective results with a manageable toxicity.
Tumors accumulate high levels of mutant p53 (mutp53), which contributes to mutp53 gain-of-function properties. The mechanisms that underlie such excessive accumulation are not fully understood. To ...discover regulators of mutp53 protein accumulation, we performed a large-scale RNA interference screen in a Burkitt lymphoma cell line model. We identified transformation/transcription domain-associated protein (TRRAP), a constituent of several histone acetyltransferase complexes, as a critical positive regulator of both mutp53 and wild-type p53 levels. TRRAP silencing attenuated p53 accumulation in lymphoma and colon cancer models, whereas TRRAP overexpression increased mutp53 levels, suggesting a role for TRRAP across cancer entities and p53 mutations. Through clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 screening, we identified a 109-amino-acid region in the N-terminal HEAT repeat region of TRRAP that was crucial for mutp53 stabilization and cell proliferation. Mass spectrometric analysis of the mutp53 interactome indicated that TRRAP silencing caused degradation of mutp53 via the MDM2-proteasome axis. This suggests that TRRAP is vital for maintaining mutp53 levels by shielding it against the natural p53 degradation machinery. To identify drugs that alleviated p53 accumulation similarly to TRRAP silencing, we performed a small-molecule drug screen and found that inhibition of histone deacetylases (HDACs), specifically HDAC1/2/3, decreased p53 levels to a comparable extent. In summary, here we identify TRRAP as a key regulator of p53 levels and link acetylation-modifying complexes to p53 protein stability. Our findings may provide clues for therapeutic targeting of mutp53 in lymphoma and other cancers.
•The HAT complex member TRRAP is vital for maintaining high p53 levels by shielding it against the natural p53 degradation machinery.•Acetylation-modifying complexes regulate p53 protein stability, which may provide a basis for therapeutic targeting of mutant p53.
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Changes in arterial blood pressure induced by mechanical ventilation allow assessment of cardiac preload. In this study, stroke volume variation (SVV), which is the percentage change between the ...maximal and minimal stroke volumes (SV) divided by the average of the minimum and maximum over a floating period of 30 s, continuously displayed by the PiCCO continuous cardiac output monitor, was evaluated as a predictor of fluid responsiveness. Fifteen patients undergoing brain surgery were included. During surgery, graded volume loading was performed with each volume loading step (VLS) consisting of 100 mL of 6% hydroxyethylstarch given for 2 min. Successive responsive VLSs were performed (increase in SV > 5% after a VLS) until a change in SV of < 5 % was reached (nonresponsive). A total of 140 VLSs were performed. Responsive and nonresponsive VLSs differed in their pre-VLS values of systolic blood pressure, SV, and SVV, but not in the values of heart rate and central venous pressure. By using receiver operating characteristic analysis, the area under the curve for SVV (0.870, 95% confidence interval CI: 0.809 to 0.903) was statistically more than those for central venous pressure (0.493, 95% CI: 0.397 to 0.590, P = 7 x 10(-10)), heart rate (0.593, 95% CI: 0.443 to 0.635, P = 5.7 x 10(-10)), and systolic blood pressure (0.729, 95% CI: 0.645 to 0.813, P: = 4.3 x 10(-3)). An SVV value of 9.5% or more, will predict an increase in the SV of at least 5% in response to a 100-mL volume load, with a sensitivity of 79% and a specificity of 93%.
Stroke volume variation may be used as a continuous preload variable and in combination with the continuously measured cardiac output, defining on-line the most important characteristics of cardiac function, allowing for optimal fluid management.
Purpose
Spondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in
ACP5.
We aimed to provide a survey of the skeletal, neurological and immune manifestations of ...this disease in a cohort of molecularly confirmed cases.
Methods
We compiled clinical, genetic and serological data from a total of 26 patients from 18 pedigrees, all with biallelic
ACP5
mutations.
Results
We observed a variability in skeletal, neurological and immune phenotypes, which was sometimes marked even between affected siblings. In total, 22 of 26 patients manifested autoimmune disease, most frequently autoimmune thrombocytopenia and systemic lupus erythematosus. Four patients were considered to demonstrate no clinical autoimmune disease, although two were positive for autoantibodies. In the majority of patients tested we detected upregulated expression of interferon-stimulated genes (ISGs), in keeping with the autoimmune phenotype and the likely immune-regulatory function of the deficient protein tartrate resistant acid phosphatase (TRAP). Two mutation positive patients did not demonstrate an upregulation of ISGs, including one patient with significant autoimmune disease controlled by immunosuppressive therapy.
Conclusions
Our data expand the known phenotype of SPENCD. We propose that the OMIM differentiation between spondyloenchondrodysplasia and spondyloenchondrodysplasia with immune dysregulation is no longer appropriate, since the molecular evidence that we provide suggests that these phenotypes represent a continuum of the same disorder. In addition, the absence of an interferon signature following immunomodulatory treatments in a patient with significant autoimmune disease may indicate a therapeutic response important for the immune manifestations of spondyloenchondrodysplasia.
•One-fifth of the patients died in the first 2 months after diagnosis.•The overall survival of those who survived the first 3 months was 22.5 months.•There was a survival advantage for those who ...received IMiD and for those who underwent hematopoietic cell transplantation.•In multivariate analysis, low performance status and increased uric acid were also associated with shorter overall survival.
Primary plasma cell leukemia (PPCL) is a rare form of multiple myeloma with a dismal prognosis. This retrospective multi-center study examines the national experience of PPCL in the era of novel agents. During 2002–2016, thirty-nine patients with PPCL were identified in 11 Israeli centers. One-fifth of them died in the first 2 months after diagnosis. The overall survival (OS) of those who survived the first 3 months was 22.5 months. About 70% of patients received at least one type of immunomodulatory drug (IMiD) and similarly proteasome inhibitor (PI) during treatment. There was a survival advantage for those who received IMiD but not for those who received PI or other type of standard dose chemotherapy. In multivariate analysis, low performance status and increased uric acid were also associated with shorter OS. In conclusion, this study demonstrates favorable impact of treatment with IMiDs and hematopoietic cell transplantation on the survival of PPCL patients.
yagil d., luria g., admi h., moshe‐eilon y. & linn s. (2010) Parents, spouses, and children of hospitalized patients: evaluation of nursing care. Journal of Advanced Nursing 66(8), 1793–1801.
Title. ...Parents, spouses, and children of hospitalized patients: evaluation of nursing care.
Aim. This paper is a report of a study of the effect of kinship type and gender on family members’ evaluation of nursing care for patients and their families in hospital units.
Background. With increasing competition in the healthcare system, hospitals attribute great importance to client satisfaction, which is strongly related to the quality of nursing care. However, to date there has been little research into family members’ evaluation of nursing care.
Methods. Questionnaires were administered to spouses, parents and children (n = 441) of hospitalized patients in three Israeli hospitals during 2007–2008.
Results. Kinship type interacted with gender in affecting family members’ evaluation of the quality of nursing care. Among men, husbands were the most satisfied with nursing behaviour, treatment of the patients, and the information they receive. Fathers were the least satisfied. Overall family evaluation of the service was predicted by their evaluation of caring, treatment, and the patient’s environment; departmental reputation was predicted by evaluation of treatment.
Conclusion. Nurses should be trained to develop sensitivity to the diverse expectations and needs of relatives, as well as awareness of how their own preconceptions affect their behaviour toward patients’ families. Nurses should develop self‐awareness of possible stereotypes and prejudices that may bias their behaviour towards family members. Reactions of family members should also be included in surveys of client satisfaction with nursing care.
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