Abstract Background The cerebrospinal fluid (CSF) biomarkers amyloid beta 1–42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. ...However, there are large variations in biomarker measurements among and within laboratories. Methods Data from the first nine rounds of the Alzheimer's Association quality control program was used to define the extent and sources of analytical variability. In each round, three CSF samples prepared at the Clinical Neurochemistry Laboratory (Mölndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection. Results A total of 84 laboratories participated. Coefficients of variation (CVs) between laboratories were around 20% to 30%; within-run CVs, less than 5% to 10%; and longitudinal within-laboratory CVs, 5% to 19%. Interestingly, longitudinal within-laboratory CV differed between biomarkers at individual laboratories, suggesting that a component of it was assay dependent. Variability between kit lots and between laboratories both had a major influence on amyloid beta 1–42 measurements, but for total tau and phosphorylated tau, between-kit lot effects were much less than between-laboratory effects. Despite the measurement variability, the between-laboratory consistency in classification of samples (using prehoc-derived cutoffs for AD) was high (>90% in 15 of 18 samples for ELISA and in 12 of 18 samples for xMAP). Conclusions The overall variability remains too high to allow assignment of universal biomarker cutoff values for a specific intended use. Each laboratory must ensure longitudinal stability in its measurements and use internally qualified cutoff levels. Further standardization of laboratory procedures and improvement of kit performance will likely increase the usefulness of CSF AD biomarkers for researchers and clinicians.
In this study. we aimed to detect vestibular schwannomas (VSs) in individual magnetic resonance imaging (MRI) slices by using a 2D-CNN. A pretrained CNN (ResNet-34) was retrained and internally ...validated using contrast-enhanced T1-weighted (T1c) MRI slices from one institution. In a second step, the model was externally validated using T1c- and T1-weighted (T1) slices from a different institution. As a substitute, bisected slices were used with and without tumors originating from whole transversal slices that contained part of the unilateral VS. The model predictions were assessed based on the categorical accuracy and confusion matrices. A total of 539, 94, and 74 patients were included for training, internal validation, and external T1c validation, respectively. This resulted in an accuracy of 0.949 (95% CI 0.935-0.963) for the internal validation and 0.912 (95% CI 0.866-0.958) for the external T1c validation. We suggest that 2D-CNNs might be a promising alternative to 2.5-/3D-CNNs for certain tasks thanks to the decreased demand for computational power and the fact that there is no need for segmentations. However, further research is needed on the difference between 2D-CNNs and more complex architectures.
BACKGROUND/AIMTo evaluate patients and treatment characteristics as well as clinical outcome in patients with intracranial metastases from prostate cancer (PCA) treated with palliative radiotherapy. ...PATIENTS AND METHODSFifteen patients treated for intracranial metastases of PCA were identified. The median age of patients was 69 years. 80% of patients received whole brain radiotherapy and 20% received partial brain radiotherapy. Clinical outcome was assessed. Univariate analysis was performed to analyze the impact of patient specific parameters on survival. RESULTSThere was no >G2 acute or any late toxicity. Median time from the first diagnosis of PCA to first diagnosis of intracranial metastases was 62 months (range=15-160 months). Median survival from first diagnosis of intracranial metastases was 14 weeks (range=0-126 weeks) and 6 weeks (range=0-47 weeks) from the start of radiotherapy. In univariate analysis, survival was significantly better for patients with an Eastern Cooperative Oncology Group (ECOG) performance status 1 compared to ECOG 2-3 18 weeks (range=5-47 weeks) vs. 3 weeks (range=0-21 weeks), p=0.030 and Recursive Partitioning Analysis (RPA) class 2 compared to RPA class 3 18 weeks (range=5-47 weeks) vs. 6 weeks (range=0-21 weeks), p=0.045. CONCLUSIONOverall survival of the patients with wide-spread intracranial metastases from PCA was poor. The decision for a radiotherapy should be done on individual patient basis.
•Recent data on prostate re-irraidation using different treatment machines show good efficacy and low toxicity.•The pooled 2-year biochemical recurrence-free survival was 72 % (95 % CI: 64–92 %).•The ...pooled rate of acute GU and GI toxicity ≥ G2 were 13 % (95 % CI: 7–18 %) and 2 % (95 % CI: 0–4 %).•The pooled rate of late GU and GI toxicity ≥ G2 were 25 % (95 % CI: 14–35 %) and 5 % (95 % CI: 1–9 %).
There is increasing data on re-irradiation to the prostate using stereotactic body radiotherapy (SBRT) after definitive radiotherapy for prostate cancer, with increasing evidence on prostate re-irradiation using a C-arm LINAC or an MR LINAC in recent years. We therefore conducted this systematic review and meta-analysis on prostate re-irradiation including studies published from 2020 to 2023, to serve as an update on existing meta-analysis.
We searched the PubMed and Embase databases in October 2023 with queries including combinations of “repeat”, “radiotherapy”, “prostate”, “re-irradiation”, “reirradiation”, “re treatment”, “SBRT”, “retreatment”. Publication date was set to be from 2020 to 2023. There was no limitation regarding language. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. After data extraction, heterogeneity testing was done by calculating the I2. A random effects model with a restricted maximum likelihood estimator was used to estimate the combined effect. Funnel plot asymmetry was assessed visually and using Egger’s test to estimate the presence of publication and/or small study bias.
14 publications were included in the systematic review. The rates of acute ≥ grade 2 (G2) genitourinary (GU) and gastrointestinal (GI) toxicities reported in the included studies ranged from 0.0-30.0 % and 0.0–25.0 % respectively. For late ≥ G2 GU and GI toxicity, the ranges are 4.0–51.8 % and 0.0–25.0 %. The pooled rate of acute GU and GI toxicity ≥ G2 were 13 % (95 % CI: 7–18 %) and 2 % (95 % CI: 0–4 %). For late GU and GI toxicity ≥ G2 the pooled rates were 25 % (95 % CI: 14–35 %) and 5 % (95 % CI: 1–9 %). The pooled 2-year biochemical recurrence-free survival was 72 % (95 % CI: 64–92 %).
SBRT in the re-irradiation of radiorecurrent prostate cancer is safe and effective. Further prospective data are warranted.
E-cigarettes are primarily used by teenagers and young adults. Flavors in e-cigarettes increase their attractiveness and encourage young people and adults to start using them. This exposes young ...people in particular to the risk of nicotine addiction and various toxic substances from the aerosol of e-cigarettes. There are indications that various flavors in e-cigarettes are harmful to health, although toxicological studies are still lacking for the majority of flavors. There is a need for independent scientific investigations in this area. The scientific societies involved are calling for a ban on flavors in e-cigarettes, a ban on disposable e-cigarettes, effective regulation of the sale of e-cigarettes and effective control and implementation of the provisions for the protection of minors.
Abstract Background The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer’s disease (AD). ...However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer’s Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods The program is open for laboratories using commercially available kits for Aβ, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Mölndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure Aβ-(1-42), P-tau(181P), and T-tau), and 5 used Meso Scale Discovery with the Aβ triplex (AβN-42, AβN-40, and AβN-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.
•GATA2 ZF1 mutants A318T and G320D permit erythroid differentiation.•GATA2 ZF2 mutant L359V blocks erythroid differentiation.•Inhibition of erythropoiesis by GATA2 L359V correlates with ...downregulation of GATA1.
GATA2 zinc-finger (ZF) mutations are associated with distinct entities of myeloid malignancies. The specific distribution of these mutations points toward different mechanisms of leukemogenesis depending on the ZF domain affected. In this study, we compared recurring somatic mutations in ZF1 and ZF2. All tested ZF mutants disrupted DNA binding in vitro. In transcription assays, co-expression of FOG1 counteracted GATA2-dependent transcriptional activation, while a variable response to FOG1-mediated repression was observed for individual GATA2 mutants. In primary murine bone marrow cells, GATA2 wild-type (WT) expression inhibited colony formation, while this effect was reduced for both mutants A318T (ZF1) and L359V (ZF2) with a shift toward granulopoiesis. In primary human CD34+ bone marrow cells and in the myeloid cell line K562, ectopic expression of GATA2 L359V, but not A318T or G320D, caused a block of erythroid differentiation accompanied by downregulation of GATA1, STAT5B, and PLCG1. Our findings may explain the role of GATA2 L359V during the progression of chronic myeloid leukemia and the collaboration of GATA2 ZF1 alterations with CEBPA double mutations in erythroleukemia.
The purpose of this review is to summarize the research on the accuracy of oxygen saturation (spO
) measurements using the Apple Watch (Apple Inc., Cupertino, California). The Medline and Google ...Scholar databases were searched for papers evaluating the spO
measurements of the Apple Watch vs. any kind of ground truth and records were analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The five publications with 973 total patients that met the inclusion criteria all used the Apple Watch Series 6 and described 95% limits of agreement of +/- 2.7 to 5.9% spO
. However, outliers of up to 15% spO
were reported. Only one study had patient-level data uploaded to a public repository. The Apple Watch Series 6 does not show a strong systematic bias compared to conventional, medical-grade pulse oximeters. However, outliers do occur and should not cause concern in otherwise healthy individuals. The impact of race on measurement accuracy should be investigated.
: Many proposed algorithms for tumor detection rely on 2.5/3D convolutional neural networks (CNNs) and the input of segmentations for training. The purpose of this study is therefore to assess the ...performance of tumor detection on single MRI slices containing vestibular schwannomas (VS) as a computationally inexpensive alternative that does not require the creation of segmentations.
: A total of 2992 T1-weighted contrast-enhanced axial slices containing VS from the MRIs of 633 patients were labeled according to tumor location, of which 2538 slices from 539 patients were used for training a CNN (ResNet-34) to classify them according to the side of the tumor as a surrogate for detection and 454 slices from 94 patients were used for internal validation. The model was then externally validated on contrast-enhanced and non-contrast-enhanced slices from a different institution. Categorical accuracy was noted, and the results of the predictions for the validation set are provided with confusion matrices.
: The model achieved an accuracy of 0.928 (95% CI: 0.869-0.987) on contrast-enhanced slices and 0.795 (95% CI: 0.702-0.888) on non-contrast-enhanced slices from the external validation cohorts. The implementation of Gradient-weighted Class Activation Mapping (Grad-CAM) revealed that the focus of the model was not limited to the contrast-enhancing tumor but to a larger area of the cerebellum and the cerebellopontine angle.
: Single-slice predictions might constitute a computationally inexpensive alternative to training 2.5/3D-CNNs for certain detection tasks in medical imaging even without the use of segmentations. Head-to-head comparisons between 2D and more sophisticated architectures could help to determine the difference in accuracy, especially for more difficult tasks.
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