Purpose
In clinically node-positive breast cancer patients receiving neoadjuvant systemic therapy (NST), nodal metastases can be initially marked and then removed during surgical axillary staging. ...Marking methods vary significantly in terms of feasibility and cost. The purpose of the extended TATTOO trial was to report on the false-negative rate (FNR) of the low-cost method carbon tattooing.
Methods
The international prospective single-arm TATTOO trial included clinically node-positive breast cancer patients planned for NST from November 2017 to January 2021. For the present analysis, patients who received both the targeted procedure with or without an additional sentinel lymph node (SLN) biopsy
and
a completion axillary lymph node dissection (ALND) were selected. Primary endpoint was the FNR.
Results
Out of 172 included patients, 149 had undergone a completion ALND. The detection rate for the tattooed node was 94.6% (141 out of 149). SLN biopsy was attempted in 132 out of 149 patients with a detection rate of 91.7% (121 out of 132). SLN and tattooed node were identical in 58 out of 121 individuals (47.9%). The combined procedure, i.e. targeted axillary dissection (TAD) was successful in 147 of 149 cases (98.7%). Four out of 65 patients with a clinically node-negative status after NST had a negative TAD but metastases on ALND, corresponding to a FNR of 6.2%. All false-negative TAD procedures were performed in the first 2 years of the trial (2018–2019,
p
= 0.022).
Conclusion
Carbon tattooing is a feasible marking method for TAD with a high detection rate and an acceptably low FNR.
The TATTOO trial was preregistered as prospective trial before initiation at the University of Rostock, Germany (DRKS00013169).
Abstract
Tidal range barrage is a well-recognized approach to extract energy from tides in a large scale. Nevertheless, the complexity of tide oscillation poses a challenge to efficaciously regulate ...this type of plants. Optimization of the process control may result in enhancement of energy yield with low influences on environment. This paper presents a framework where the whole tidal-electric system is modelled and coupled with a nonlinear model predictive control (NMPC) strategy to determine the optimal state of turbo-generators over a complete spring-neap cycle in a month. The method allows the system model to be nonlinear and dynamic under tight constraints, which would be extremely appropriate for the deployment of this highly predictable but frequently varied energy. A potential bay in Norway is chosen to be a proposal site to verify the benefits of the control strategy, by comparing the energy extraction between a simple barrage without sluices and a conventional one with sluices assembly. Results show the conventional barrage type is superior with respect to energy generation, while keeping the turbine blade diameter as as factor. For excessively large turbines, though, the revenue may be curtailed by costs due to environmental factors, and turbine construction.
Molecular analyses have shown that tumours diagnosed as supratentorial primitive neuro-ectodermal tumours of the central nervous system (CNS-PNETs) in the past represent a heterogenous group of rare ...childhood tumours including high-grade gliomas (HGG), ependymomas, atypical teratoid/rhabdoid tumours (AT/RT), CNS neuroblastoma with forkhead box R2 (FOXR2) activation and embryonal tumour with multi-layered rosettes (ETMR). All these tumour types are rare and long-term clinical follow-up data are sparse. We retrospectively re-evaluated all children (0-18 years old) diagnosed with a CNS-PNET in Sweden during 1984-2015 and collected clinical data.
In total, 88 supratentorial CNS-PNETs were identified in the Swedish Childhood Cancer Registry and from these formalin-fixed paraffin-embedded tumour material was available for 71 patients. These tumours were histopathologically re-evaluated and, in addition, analysed using genome-wide DNA methylation profiling and classified by the MNP brain tumour classifier.
The most frequent tumour types, after histopathological re-evaluation, were HGG (35%) followed by AT/RT (11%), CNS NB-FOXR2 (10%) and ETMR (8%). DNA methylation profiling could further divide the tumours into specific subtypes and with a high accuracy classify these rare embryonal tumours. The 5 and 10-year overall survival (OS) for the whole CNS-PNET cohort was 45% ± 12% and 42% ± 12%, respectively. However, the different groups of tumour types identified after re-evaluation displayed very variable survival patterns, with a poor outcome for HGG and ETMR patients with 5-year OS 20% ± 16% and 33% ± 35%, respectively. On the contrary, high PFS and OS was observed for patients with CNS NB-FOXR2 (5-year 100% for both). Survival rates remained stable even after 15-years of follow-up.
Our findings demonstrate, in a national based setting, the molecular heterogeneity of these tumours and show that DNA methylation profiling of these tumours provides an indispensable tool in distinguishing these rare tumours. Long-term follow-up data confirms previous findings with a favourable outcome for CNS NB-FOXR2 tumours and poor chances of survival for ETMR and HGG.
Cholesterol-rich clusters of SNARE (soluble NSF attachment protein receptor) proteins have been implicated as being important for exocytosis. Here we demonstrate the significance of cholesterol for ...normal biphasic insulin secretion in mouse β cells by removal of cholesterol from the plasma membrane using methyl-β-cyclodextrin (MBCD). Maximal inhibition of insulin secretion in static incubations was achieved using 0.1 mM MBCD. In in situ pancreatic perfusion measurements, both first and second phase insulin secretions were reduced by ~50% (P<0.05). This was accompanied by a reduced number of docked large dense core vesicles (LDCVs) (~40%; P<0.01) and a reduced exocytotic response (>50%; P<0.01). Further, subcellular fractionations demonstrated movement of the synaptosomal protein of 25 kDa (SNAP-25) from the plasma membrane to the cytosol after MBCD treatment. The inhibitory actions of MBCD were counteracted by subsequent addition of cholesterol. We hypothesize that desorption of cholesterol leads to the disturbance of a basic exocytotic mechanism partly due to migration of SNAP-25, and we conclude that insulin secretion is highly sensitive to changes in plasma membrane cholesterol.--Vikman, J., Jimenez-Feltström, J., Nyman, P., Thelin, J., Eliasson, L. Insulin secretion is highly sensitive to desorption of plasma membrane cholesterol.
By the sequential action of dCTP deaminase and dUTPase, dCTP is converted to dUMP, the precursor of thymidine nucleotides. In addition, dUTPase has an essential role as a safeguard against uracil ...incorporation in DNA. The putative dCTP deaminase (MJ0430) and dUTPase (MJ1102) from the hyperthermophilic archaeon Methanocaldococcus jannaschii were overproduced in Escherichia coli. Unexpectedly, we found the MJ0430 protein capable of both reactions, i.e. hydrolytic deamination of the cytosine ring and hydrolytic cleavage of the phosphoanhydride bond between the α- and β-phosphates. When the reaction was followed by thin layer chromatography using 3HdCTP as substrate, dUMP and not dUTP was identified as a reaction product. In the presence of unlabeled dUTP, which acted as an inhibitor, no label was transferred from 3HdCTP to the pool of dUTP. This finding strongly suggests that the two consecutive steps of the reaction are tightly coupled within the enzyme. The hitherto unknown bifunctionality of the MJ0430 protein appears beneficial for the cells because the toxic intermediate dUTP is never released. The MJ0430 protein also catalyzed the hydrolysis of dUTP to dUMP but with a low affinity for the substrate (Km >100 μm). According to limited proteolysis, the C-terminal residues constitute a flexible region. The other protein investigated, MJ1102, is a specific dUTPase with a Km for dUTP (0.4 μm) comparable in magnitude with that found for previously characterized dUTPases. Its physiological function is probably to degrade dUTP derived from other reactions in nucleotide metabolism.
Patients with sentinel-node metastasis at the time of breast-cancer surgery may undergo axillary dissection to remove more nodes, which can lead to side effects. In a trial, the additional surgery ...did not prolong survival.
Visual difficulties are common after brain tumors, despite a lack of visual complaints at diagnosis. These include difficulties with eye movements, visual coordination, vergence, accommodation, and ...photophobia, in addition to more obvious problems such as visual field defects.This case report presents the results of a thorough neuro-visual evaluation in a boy with sequelae after a brain tumor including intermittent double vision that was not explained by routine visual examination. Subjective complaints included poor reading perseverance, intermittent blurred and double vision, headache around the eyes when performing near activities, less efficient eye movement behavior in reading tasks, and increased sensitivity to visual motion. The patient participated in a multidisciplinary visual rehabilitation program that included reading glasses with prism compensation and tinted glasses, as well as training with the aim of improving eye teaming, near vision functions, and perseverance in eye movements.The patient responded quickly to the vision therapy program, with positive changes after just four weeks. Repeated neuro-visual evaluations over eight months showed remarkable improvements that were stable over time. This encouraging case report supports the notion that neuro-visual evaluation and rehabilitation should be included in the follow-up of patients after brain tumors.
Background
The elapsed time taken to diagnose tumors of the central nervous system in children and adolescents varies widely. The aim of the present study was to investigate such diagnostic time ...intervals at a national level in Sweden as they correlate with clinical features.
Methods
Data prospectively accumulated over a 4‐year period in the Swedish Childhood Cancer Registry from patients aged 0–18 years were pooled, and diagnostic time intervals were analyzed considering tumor location, tumor type, patient age and sex, initial symptoms, and clinical timelines. All six pediatric oncology centers in Sweden contributed to collection of data. Time points for calculating the total diagnostic interval (TDI) defined as the time from symptom onset to diagnosis were reported in 257 of 319 patients (81%).
Results
The time from symptom onset to the first healthcare consultation, median 2.6 weeks, did not vary significantly between patients categorized according to tumor type or location. The median TDI was 8.3 weeks for the 4‐year study period. Patients with optic pathway glioma (TDI 26.6 weeks), those with tumors of the spinal cord (TDI 25.9 weeks), and those with midline tumors (TDI 24.6 weeks) had the longest lead times. Additionally, older age, too few initial symptoms, and seeking initial redress outside an emergency ward were factors associated with a longer time to diagnosis.
Conclusion
This study identified several factors associated with delayed diagnosis of central nervous system tumors among Swedish children and adolescents. These novel data ought to help direct future efforts toward clinical improvement.
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