Biological and radiological exploration and management of non-functioning pituitary adenoma

AbstractNon-functioning pituitary adenoma may be totally asymptomatic and discovered “incidentally” during radiological examination for some other indication, or else induce tumoral signs with compression of the optic chiasm and pituitary dysfunction. Non-functioning adenomas are mainly gonadotroph, but may also be “silent”. Treatment strategy depends on initial clinical, biological, ophthalmological and radiological findings. The present French Society of Endocrinology Consensus work-group sought to update the pitfalls associated with hormone assay and outline a hormonal exploration strategy for diagnosis and follow-up, without overlooking the particularities of silent adenoma. We also drew up basic rules for initial exploration and radiological follow-up of both operated and non-operated pituitary adenomas

Evidence of Overcharging in the Complexation between Oppositely Charged Polymers and Surfactants

We report on the complexation between charged-neutral block copolymers and oppositely charged surfactants studied by small-angle neutron scattering. Two block copolymers/surfactant systems are investigated, poly(acrylic acid)-b-poly(acrylamide) with dodecyltrimethylammonium bromide and poly(trimethylammonium ethylacrylate methylsulfate)-b-poly(acrylamide) with sodium dodecyl sulfate. The two systems are similar in terms of structure and molecular weight but have different electrostatic charges. The neutron scattering data have been interpreted in terms of a model that assumes the formation of mixed polymer-surfactant aggregates, also called colloidal complexes. These complexes exhibit a core-shell microstructure, where the core is a dense coacervate microphase of micelles surrounded by neutral blocks. Here, we are taking advantage of the fact that the complexation results in finite-size aggregates to shed some light on the complexation mechanisms. In order to analyze quantitatively the neutron data, we develop two different approaches to derive the number of surfactant micelles per polymer in the mixed aggregates and the distributions of aggregation numbers. With these results, we show that the formation of the colloidal complex is in agreement with the overcharging predictions. In both systems, the amount of polyelectrolytes needed to build the core-shell colloids always exceeds the number that would be necessary to compensate the charge of the micelles. For the two polymer-surfactant systems investigated, the overcharging ratios are 0.66 and 0.38.Comment: 20 pages, 7 Figures, 6 Table

Interferon beta 1b following natalizumab discontinuation: one year, randomized, prospective, pilot trial

Background: Natalizumab (NTZ) discontinuation leads to multiple sclerosis reactivation. The objective of this study is to compare disease activity in MS patients who continued on NTZ treatment to those who were switched to subcutaneous interferon 1b (IFNB) treatment. Methods: 1-year randomized, rater-blinded, parallel-group, pilot study (ClinicalTrial.gov ID: NCT01144052). Relapsing remitting MS patients on NTZ for ≥12 months who had been free of disease activity on this therapy (no relapses and disability progression for ≥6 months, no gadolinium-enhancing lesions on baseline MRI) were randomized to NTZ or IFNB. Primary endpoint was time to first on-study relapse. Additional clinical, MRI and safety parameters were assessed. Analysis was based on intention to treat. Results: 19 patients (NTZ n=10; IFNB n=9) with similar baseline characteristics were included. 78% of IFNB treated patients remained relapse free (NTZ group: 100%), and 25% remained free of new T2 lesions (NTZ group: 62.5%). While time to first on-study relapse was not significantly different between groups (p=0.125), many secondary clinical and radiological endpoints (number of relapses, proportion of relapse free patients, number of new T2 lesions) showed a trend, or were significant (new T2 lesions at month 6) in favoring NTZ. Conclusions: De-escalation therapy from NTZ to IFNB over 1 year was associated with some clinical and radiological disease recurrence. Overall no major safety concerns were observed

MSSEG-2 challenge proceedings: Multiple sclerosis new lesions segmentation challenge using a data management and processing infrastructure

International audienceThis proceedings book gathers methodological papers describing the segmenta-tion methods evaluated at the second MICCAI Challenge on Multiple Sclerosisnew lesions segmentation challenge using a data management and processinginfrastructure. This challenge took place as part of an effort of the OFSEP1(French registry on multiple sclerosis aiming at gathering, for research purposes,imaging data, clinical data and biological samples from the French populationof multiple sclerosis subjects) and FLI2(France Life Imaging, devoted to setupa national distributed e-infrastructure to manage and process medical imagingdata). These joint efforts are directed towards automatic segmentation of MRIscans of MS patients to help clinicians in their daily practice. This challengetook place at the MICCAI 2021 conference, on September 23rd 2021.More precisely, the problem addressed in this challenge is as follows. Con-ventional MRI is widely used for disease diagnosis, patient follow-up, monitoringof therapies, and more generally for the understanding of the natural history ofMS. A growing literature is interested in the delineation of new MS lesions onT2/FLAIR by comparing one time point to another. This marker is even morecrucial than the total number and volume of lesions as the accumulation of newlesions allows clinicians to know if a given anti-inflammatory DMD (disease mod-ifying drug) works for the patient. The only indicator of drug efficacy is indeedthe absence of new T2 lesions within the central nervous system. Performingthis new lesions count by hand is however a very complex and time consumingtask. Automating the detection of these new lesions would therefore be a majoradvance for evaluating the patient disease activity.Based on the success of the first MSSEG challenge, we have organized aMICCAI sponsored online challenge, this time on new MS lesions detection3.This challenge has allowed to 1) estimate the progress performed during the2016 - 2021 period, 2) extend the number of patients, and 3) focus on the newlesions crucial clinical marker. We have performed the evaluation task on a largedatabase (100 patients, each with two time points) compiled from the OFSEPcohort with 3D FLAIR images from different centers and scanners. As in ourprevious challenge, we have conducted the evaluation on a dedicated platform(FLI-IAM) to automate the evaluation and remove the potential biases due tochallengers seeing the images on which the evaluation is made

Double reading of outsourced CT/MR radiology reports

OBJECTIVES: Our objective was to determine disagreement rates in radiological reports provided by using a double-reading protocol in a national teleradiology company. METHODS: From January 2015 to July 2016, 134169 radiological exams from 36 French centers, benefited outsourced interpretations by certified radiologists, in both regular and after-hours activities. Of these, 2040 CT and MR-scans (1.5%) were subjected to a second opinion by other radiologists in the field of their anatomical specialty (cerebral, thoracic, abdominal-pelvic, and osteoarticular). A five-point agreement scale graded from 0 to 4 was assigned for each exam. Disagreements were considered as minor if no clinical consequence for patient (scores 1 and 2) and major if potential clinical consequence (score 3 and 4). Independent radiologists performed a retrospective analysis and a stratified statistical analysis. RESULTS: Double reading was performed on CT-scans (n = 934/2040, 45.8%) and MR-scans (n = 1106/2040, 54.2%) performed in regular (80.1%) and after-hours activities (19.9%). Disagreement scores occurred in 437 exams (21.4%), including major disagreements in 59 (2.9%). Among these, 48/754 were assigned by the thoracic second reader (6.4%), 6/70 by the abdominal-pelvic second reader (8.6%), 3/901 by the osteoarticular second reader (0.3%), and 2/315 by the cerebral second reader (0.6%), with statistical significant difference. No additional disagreement rate was observed in regular and after-hours activities (P = 0.63). CONCLUSIONS: Double-reading of outsourced CT and MRI interpretations yielded 21.4% disagreement rate, with potential clinical consequence for patient in 2,9% of the cases. These results are in accordance with those previously reported and suggests that quality assurance of outsourced interpretations is needed

MRC Clinical Trials Unit, UK

www.ias-cipher.org

Validation of 2006 WHO Prediction Scores for True HIV Infection in Children Less than 18 Months with a Positive Serological HIV Test

All infants born to HIV-positive mothers have maternal HIV antibodies, sometimes persistent for 18 months. When Polymerase Chain Reaction (PCR) is not available, August 2006 World Health Organization (WHO) recommendations suggest that clinical criteria may be used for starting antiretroviral treatment (ART) in HIV seropositive children <18 months. Predictors are at least two out of sepsis, severe pneumonia and thrush, or any stage 4 defining clinical finding according to the WHO staging system.From January 2005 to October 2006, we conducted a prospective study on 236 hospitalized children <18 months old with a positive HIV serological test at the national reference hospital in Kigali. The following data were collected: PCR, clinical signs and CD4 cell count. Current proposed clinical criteria were present in 148 of 236 children (62.7%) and in 95 of 124 infected children, resulting in 76.6% sensitivity and 52.7% specificity. For 87 children (59.0%), clinical diagnosis was made based on severe unexplained malnutrition (stage 4 clinical WHO classification), of whom only 44 (50.5%) were PCR positive. Low CD4 count had a sensitivity of 55.6% and a specificity of 78.5%.As PCR is not yet widely available, clinical diagnosis is often necessary, but these criteria have poor specificity and therefore have limited use for HIV diagnosis. Unexplained malnutrition is not clearly enough defined in WHO recommendations. Extra pulmonary tuberculosis (TB), almost impossible to prove in young children, may often be the cause of malnutrition, especially in HIV-affected families more often exposed to TB. Food supplementation and TB treatment should be initiated before starting ART in children who are staged based only on severe malnutrition

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead