We hypothesized that clinical risk factors could be identified within 2 weeks of onset of severe (stage 3 or 4) acute gut GVHD for identifying a patient population with a very poor outcome. Among ...1462 patients who had allogeneic hematopoietic cell transplantation (HCT) between January 2000 and December 2005, 116 (7.9%) developed stage 3-4 gut GVHD. The median time for onset of stage 3-4 gut GVHD was 35 (4-135) days after allogeneic HCT. Eighty-five of the 116 patients (73%) had corticosteroid resistance before or within 2 weeks after the onset of stage 3-4 gut GVHD. Significant risk factors for mortality included corticosteroid resistance (hazards ratio (HR)=2.93; P=0.0005), age >18 years (HR=4.95; P=0.0004), increased serum bilirubin (HR 2.53; P=0.0001) and overt gastrointestinal bleeding (HR 2.88; P=0.0004). Among patients with stage 3-4 gut GVHD, the subgroup with 0, 1 or 2 risk factors had a favorable prognosis, whereas the subgroup with 3 or 4 risk factors had a dismal prognosis. This information should be considered in designing future studies of severe gut GVHD and in counseling patients about prognosis.
We propose three innovative SOI Tunnel FET architectures to solve the recurrent issue of low ION and degraded subthreshold slope measured on TFETs. These are evaluated and compared with a standard ...TFET structure (with lateral tunneling) using the Sentaurus TCAD tool. Extending the source (anode) at the bottom of the body region generates vertical band-to-band tunneling. Moreover, reducing the vertical distance between the extension and the gate oxide (Lrt) yields a very steep slope and higher ION compared to a device with only lateral tunneling, but only for gate lengths longer than 100 nm. Using an ultrahigh boron dopant concentration (1021 cm−3) thin layer at the bottom for extremely small body thickness (TSi < 7 nm), increases ION even for small gate lengths (LG < 100 nm). The implementation of an embedded tip in the source enhances the maximum electric field at the source/channel junction, but the impact on the performance is limited because the tunneling area is not increased. Therefore, this architecture provides a performance similar to a standard TFET. TCAD simulations using SiGe with different germanium concentrations (30% and 50%) and pure germanium, instead of silicon, show an increase of the interband tunneling current when using an ultrahigh dopant concentration thin boron layer for small gate lengths (LG < 50 nm). The reduction of the tunneling current using a relatively thick channel (11–7 nm) can be compensated by using a higher germanium concentration to reduce the energy bandgap. However, this will increase the density of defects causing a TAT tunneling instead of interband tunneling, jeopardizing the possibility of achieving a subthreshold swing below 60 mV/dec.
Background
Cytokine release syndrome (CRS) is a common adverse event of CAR T cell or bispecific antibody (bsAb) therapy. Anti-IL6/IL6R drugs are used in the management of auto-immune diseases. Some ...reports showed increased risk of bacterial infection in this context. In onco-hematology, there are few data about the occurrence of infection after administration of an anti-IL6/IL6R for CRS.
Methods
We retrospectively reviewed all consecutive patients treated in Gustave Roussy Cancer Campus between 2018 and 2021, who received anti-IL6/IL6R for CRS due to bsAb in phase I clinical trials or adoptive cellular therapy (ACT). We constituted a control group including all the patients treated in the same clinical trials or standard of care ACT, naïve of anti-IL6/IL6R.
Results
Fifty-two patients have been included. In the anti-IL6/IL6R group (
n
= 26), five patients developed a grade 2 to 5 infection within a month after anti-IL6/IL6R treatment, including two grade 5 infections. In the control group (
n
= 26), only one patient had a grade 3 infection. The two patients who had grade 5 infections were treated for diffuse large B cell lymphoma (DLBCL), one with bsAb and the other with CAR T cell. Fifty percent (3/6) of DLBCL patients who received an anti-IL6/IL6R presented an infection, one of which was a grade 5. In solid tumor patients treated with bsAb and anti-IL6/IL6R, only one patient (/9, 11%) developed a grade 2 viral infection.
Conclusion
It seems that the use of anti-IL6/IL6R in CRS secondary to bsAb administration in solid tumors patients does not significantly increase the risk of infection, as opposed to DLBCL patients where secondary infection might be a concern.
Nous rapportons ici le premier patient français avec une polyneuropathie avec anticorps anti-Myelin-Associated Glycoprotein (PN-MAG) traité par autogreffe de cellules souches hématopoïétiques (ACSH). ...Il s’agit d’un homme de 60 ans aux antécédents de maladie thromboembolique veineuse sous apixaban et de syndrome d’apnée du sommeil. Le diagnostic de PN-MAG associé à une gammapathie IgM monoclonale de signification indéterminée (MGUS) est posé en 2010 devant une ataxie proprioceptive et des paresthésies des pieds apparues en 2009. Une atteinte motrice apparaît rapidement aux membres inférieurs et le patient marche avec une canne et des orthèses de cheville à partir de 2012. Le patient est traité par immunoglobulines polyvalentes intraveineuses (IgIV) de 2011 à 2012 sans amélioration clinique. Une atteinte sensitivomotrice des membres supérieurs apparaît en 2016, i.e., des paresthésies et une amyotrophie des 2 mains associées à un tremblement d’action qui conduisent notamment à la perte de l’écriture. Un traitement par rituximab semestriel est débuté en 2016, avec un total de 6 perfusions, sans amélioration des symptômes. L’indication d’ACSH est retenue après discussion avec le patient et avec le réseau MATHEC (maladies auto-immunes et thérapies cellulaires). Le score ONLS (Overall Neurologic Limitation Scale) prégreffe était estimé à 5 (3+2)/12 et l’électroneuromyogramme (ENMG) prégreffe montrait, outre une polyneuropathie démyélinisante sévère des 4 membres, une perte axonale sévère aux membres inférieurs. Le pic IgM était à 1g/L et les anticorps anti-MAG > 70,000 BTU. La mobilisation des cellules souches hématopoïétiques fut réalisée en janvier 2020 par cyclophosphamide puis aphérèse suivie un mois plus tard par un conditionnement par cyclophosphamide 200mg/kg et thymoglobuline 6,5mg/kg puis réinjection de cellules souches. Les suites de la greffe ont été simples, sans nécessité de support transfusionnel avec une sortie d’aplasie à j12 post-réinjection. Les complications précoces (< 100jours après la greffe) étaient une infection urinaire à Escherichia coli d’évolution rapidement favorable après antibiothérapie adaptée et une embolie pulmonaire à l’arrêt de l’anticoagulation efficace 3 mois après la greffe. Le tremblement des membres supérieurs et les paresthésies des deux mains disparurent quelques semaines après la greffe et le patient put à nouveau boutonner une chemise, ouvrir une bouteille, écrire, manipuler des clefs, autant de fonctions qu’il avait perdues avant la greffe (score ONLS global à 3). Deux ans après la greffe, le score ONLS est toujours estimé à 3(1+2)/12, il n’y a pas eu de récupération aux membres inférieurs, le taux d’anticorps anti-MAG diminue (17,202 BTU à M12, 28,713 à M24, 59,668 à M36) & le pic IgM disparaît. La PN-MAG est la plus fréquente des neuropathies associées aux gammapathies monoclonales dont la physiopathologie est directement liée à l l’effet pathogénique des anticorps anti-MAG sur la gaine de myéline, suggérant l’existence d’un clone B sous-jacent 1. De ce fait, les traitements les plus utilisés à l’heure actuelle sont dirigés contre la lignée B notamment le rituximab seul ou en association. Il n’existe cependant pas de traitement clairement codifié. D’autres thérapies sont prometteuses, comme les inhibiteurs de Bruton tyrosine Kinase, notamment l’ibrutinib, par analogie avec la maladie de Waldenstrom. Son efficacité est toutefois limitée chez les patients non mutés MYD88. Il existe, cependant, un certain nombre de patient pour lesquels il n’existe pas de clone spécifiquement identifié, ni de mutation MYD88 2 suggérant un mécanisme polyclonal auto-immun. L’autogreffe de cellules souches hématopoïétiques est actuellement possible en 3e ligne de traitement dans d’autres neuropathies dysimmunitaires, notamment les polyradiculonévrites inflammatoires démyélinisantes chroniques (PIDC). L’ACSH permet une « réinitialisation » du système immunitaire. Un seul cas de PN-MAG traitée par ACSH a été rapporté jusqu’à présent : le traitement fut efficace, mais le patient présenta une rechute clinique 3 ans après la greffe 3. Dans le cas présenté ici, l’ACSH a été particulièrement efficace, même avec 3 ans de recul.
Le cas rapporté ici montre que l’ACSH est une alternative thérapeutique pertinente pour les patients avec une PN-MAG sévère résistante aux traitements usuels.
BACKGROUND:At 07:39 am on March 11th, 2004, ten terrorist bomb explosions occurred almost simultaneously in four commuter trains in Madrid, Spain, killing instantly 177 people and injuring >2,000. ...There were 14 subsequent in-hospital deaths, bringing the definite death toll to 191 victims. This article describes the organization of the clinical management and patterns of injuries in casualties who were taken to the closest hospital, with emphasis on the critical patient population.
RESULTS:There were 312 patients taken to that center, and 91 were hospitalized, 89 of them (28.5%) for >24 hrs. Sixty-two patients only had superficial bruises or emotional shock, but the remaining 250 patients had more severe lesions. The data on 243 of the latter form the basis of this report. Tympanic perforation occurred in 41% of 243 victims with moderate-to-severe trauma, chest injuries in 40%, shrapnel wounds in 36%, fractures in 18%, first- or second-degree burns in 18%, eye lesions in 18%, head trauma in 12%, and abdominal injuries in 5%. Between 8:00 am and 5:00 pm, 34 surgical interventions were performed on 32 victims. Twenty-nine casualties (12% of the total or 32.5% of those hospitalized) were deemed in critical condition, and two of them died within minutes of arrival. The other 27 survived to be admitted to intensive care units, and three of them died, bringing the critical mortality rate to 17.2% (5/29). The mean Injury Severity Score and Acute Physiology and Chronic Health Evaluation II scores of critical patients were 34 and 23, respectively. Among these critical patients, soft-tissue and musculoskeletal injuries predominated in 85% of cases, ear blast injury was identified in 67%, and blast lung injury was present in 63% (17 cases). Fifty-two percent suffered head trauma.
CONCLUSIONS:There was probably an overtriage to the closest hospital, and the time of the blasts proved crucial for the adequacy of the medical and surgical response. The number of blast lung injuries seen is probably the largest reported by a single institution, and the critical mortality rate was reasonably low.
There has been growing scientific evidence in recent years that schizophrenia and bipolar disorder share clinical, cognitive, neuroimaging and genetic characteristics. This overlap might also be ...present in their offspring, who have an increased risk of developing both disorders. Comparing the characteristics of these samples may have important implications for understanding etiological processes. This study aimed to assess the development of cognitive functions over two years in a sample of child and adolescent offspring of patients diagnosed with schizophrenia (SZoff) or bipolar disorder (BDoff), comparing them with a community control group (CCoff).
90 BDoff, 41 SZoff and 107 CCoff aged between 6 and 17 years were included at baseline. At the two-year follow-up, 84.9% of the sample was re-assessed (78 BDoff, 32 SZoff and 92 CCoff). All subjects were assessed with a comprehensive neuropsychological test battery at baseline and at the two-year follow-up to evaluate: intelligence quotient, working memory, processing speed, verbal memory and learning, visual memory, executive functions and sustained attention.
Processing speed, verbal memory and executive functions showed different developmental patterns among the SZoff, BDoff and CCoff groups. The SZoff group maintained baseline performances in the three variables over time, while the BDoff group presented improved processing speed and executive functioning and the CCoff group showed improvements in verbal memory and executive functions at follow-up.
These findings suggest that the development of some cognitive functions might differ between child and adolescent SZoff and BDoff, indicating different trajectories during neurodevelopment.
•The evolution of some cognitive functions may differ between offspring of patients diagnosed with schizophrenia or bipolar disorder•Offspring of patients diagnosed with schizophrenia maintained their cognitive performance over time whereas•Offspring of patients diagnosed with bipolar disorder improved their performance over time
Autism Spectrum Disorders (ASD) and psychosis share deficits in social cognition. The insular region has been associated with awareness of self and reality, which may be basic for proper social ...interactions.
Total and regional insular volume and thickness measurements were obtained from a sample of 30 children and adolescents with ASD, 29 with early onset first-episode psychosis (FEP), and 26 healthy controls (HC). Total, regional, and voxel-level volume and thickness measurements were compared between groups (with correction for multiple comparisons), and the relationship between these measurements and symptom severity was explored.
Compared with HC, a shared volume deficit was observed for the right (but not the left) anterior insula (ASD: p = 0.007, FEP: p = 0.032), and for the bilateral posterior insula: (left, ASD: p = 0.011, FEP: p = 0.033; right, ASD: p = 0.004, FEP: p = 0.028). A voxel-based morphometry (VBM) conjunction analysis showed that ASD and FEP patients shared a gray matter volume and thickness deficit in the left posterior insula. Within patients, right anterior (r = -0.28, p = 0.041) and left posterior (r = -0.29, p = 0.030) insular volumes negatively correlated with the severity of insight deficits, and left posterior insular volume negatively correlated with the severity of 'autistic-like' symptoms (r = -0.30, p = 0.028).
The shared reduced volume and thickness in the anterior and posterior regions of the insula in ASD and FEP provides the first tentative evidence that these conditions share structural pathology that may be linked to shared symptomatology.
Potentiodynamic measurements together with SEM were used to analyze susceptibility to pitting corrosion of 13CrNiMo plate metals. Volume fractions of austenite in tempered conditions affect pitting ...resistance. Characteristic potentials (critical pitting and repassivation) increase according to the retained austenite content. Results correspond to a structural refinement resulting from a double tempering procedure. A comparison is made with results from weld metal samples. The importance of this evaluation is to be able to determine pitting resistance, either in a service application, or in laboratory test programs.
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