A case of corticosteroid-dependent recurrent pericarditis with different response to two IL-1 blocking agents

Background: Recurrent pericarditis (RP) represents the most troublesome presentation of pericarditis and has a controversial pathogenesis that crosses infectious, auto-immune and auto-inflammatory pathways. It has been suggested that in some cases it might be an unrecognized auto-inflammatory disease. Recent studies have demonstrated that anakinra, an interleukin-1 receptor antagonist (IL-1RA), represents an effective treatment for the control of corticosteroid-dependent cases. Objectives: To describe a case of cortico-dependent recurrent pericarditis with a different response to two IL-1 blocking agents, anakinra and canakinumab. Methods: Case report Results: 11 years old boy who was admitted to our hospital because of acute precordial pain, orthopnea, fever and increased levels of acute phase reactants. Acute pericarditis was confirmed by echocardiography and a treatment with prednisone was started with prompt clinical improvement. Pericarditis recurred twice during steroid tapering (1mg/kg/day and 0.5mg/kg/day respectively). After exclusion of infectious origin, therapy with anakinra (2mg/kg/day) was established (to avoid long term steroid side effects) followed by dramatic clinical response and normalisation of laboratory findings despite tapering and discontinuation of prednisone. Treatment with anakinra was discontinued after 5 months with recurrence of pericarditis one week later. Anakinra was resumed with an excellent response. Five months later, while being in complete remission, anakinra was replaced with canakinumab (2mg/kg/dose) due to patient’s intolerance of daily injections. One week later, the patient experienced a new episode of pericarditis requiring corticotherapy. Two more relapses occured during steroid tapering, after 6 weeks and 2 months, in spite of the uptitration of canakinumab to 4mg/kg/dose. Anakinra was restarted with prompt clinical and biological remission and prednisone was discontinuated without recurrence of pericarditis. After further four weeks follow-up under anakinra alone, the pericarditis is still in remission. Conclusion: We describe a case of steroid-dependent RP with a dramatic therapeutic response to IL-1RA (anakinra) but without response to IL-1β monoclonal antibody (canakinumab). This unexpected observation could suggest that Il-1α might have a role in the pathogenesis of RP. The definitive potential usefulness of each IL-1 blocking agent requires confirmation in prospective controlled trials

ODS steel as structral material for high temperature nuclear reactors

Oxide dispersed strengthened (ODS) ferritic-martensitic steels are investigated as possible structural material for the future generation of High Temperature Gas Cooled Nuclear Reactors. The Ni based austenitic ODS superalloys are not considered, because of the Ni presence, which is unfavorable under neutron irradiation. ODS-steels are considered to replace other high temperature materials for tubing or structural parts. Interestingly, ODS is also considered as material being used in future fusion applications. The oxide particles serve for interfacial pinning of moving dislocations. Therefore the creep resistance is improved. In case of the usage of these materials in reactor, the behavior under irradiation must be further clarified. In this paper the effects induced by He implantation are investigated. The induced swelling is measured and the mechanical behavior of the irradiated surface is investigated. These first tests are performed at room temperature, where a clear swelling and hardening could be observed.Окисно дисперговані зміцнені (ОДЗ) феритно-мартенситні сталі досліджуються як можливі конструкційні матеріали для нового покоління високотемпературних ядерних реакторів з газовим охолодженням. Аустенітні ОДЗ-сплави на основі никелю не вивчаються завдяки никелю, присутність якого під дією опромінення небажана. ОДЗ-сталі разглядаються як можливі кандидати на заміну інших високотемпературних матеріалів для вигoтовлення трубопроводів або інших конструкційних вузлів. Цікаво, що ОДЗ-матеріали розглядаються також з точки зору їх можливого використання для майбутнього застосування в термоядерних пристроях. Окисні частки служать як міжфазні пастки для закріплення дислокацій, що рухаються. У разі використання ціх материалів в реакторі їх поведінка під опроміненням повинна вивчатись більш ретельно. В роботі досліджуються ефекти, зумовлені проникненням Не. Вимірюється зумовлене розпухання та механічні характеристики опроміненої поверхні. Ці перші дослідження були виконані при кімнатній температурі, коли можно чітко спостерігати розпухання та зміцнення.Окисно диспергированные упрочненные (ОДУ) ферритно-мартенситные стали изучались как возможные конструкционные материалы для нового поколения высокотемпературных ядерных реакторов с газовым охлаждением. Аустенитные ОДУ-суперсплавы на базе никеля не рассматривались из-за присутствия никеля, который нежелателен при нейтронном облучении. ОДУ-стали рассматривались как возможные заменители других высокотемпературных материалов для изготовления трубопроводов или других композиционных узлов. Интересно, что ОДУ рассматривается так же, как возможный кандидат для использования в термоядерных устройствах. Окисные частицы служат как межфазные ловушки для закрепления движущихся дислокаций. Поэтому сопротивление ползучести увеличивается. В случае использования этих материалов в реакторе их поведение под облучением должно изучаться более тщательно. В предлагаемой работе исследуются эффекты, обусловленные внедрением Не. Измеряется обусловленное распухание и механические характеристики облученной поверхности. Эти первые испытания были выполнены при комнатной температуре, когда можно явно наблюдать распухание и упрочнение

A Positron Emission Tomography Study of Voluntarily and Electrically Contracted Human Quadriceps

peer reviewe

Issues in Assessing Environmental Exposures to Manufactured Nanomaterials

Manufactured nanomaterials (MNs) are commonly considered to be commercial products possessing at least one dimension in the size range of 10−9 m to 10−7 m. As particles in this size range represent the smaller fraction of colloidal particles characterized by dimensions of 10−9 m to 10−6 m, they differ from both molecular species and bulk particulate matter in the sense that they are unlikely to exhibit significant settling under normal gravitational conditions and they are also likely to exhibit significantly diminished diffusivities (when compared to truly dissolved species) in environmental media. As air/water, air/soil, and water/soil intermedium transport is governed by diffusive processes in the absence of significant gravitational and inertial impaction processes in environmental systems, models of MN environmental intermedium transport behavior will likely require an emphasis on kinetic approaches. This review focuses on the likely environmental fate and transport of MNs in atmospheric and aquatic systems. Should significant atmospheric MNs emission occur, previous observations suggest that MNs may likely exhibit an atmospheric residence time of ten to twenty days. Moreover, while atmospheric MN aggregates in a size range of 10−7 m to 10−6 m will likely be most mobile, they are least likely to deposit in the human respiratory system. An examination of various procedures including the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory of colloidal particle suspension stability in water indicates that more sophisticated approaches may be necessary in order to develop aquatic exposure models of acceptable uncertainty. In addition, concepts such as Critical Coagulation Concentrations and Critical Zeta Potentials may prove to be quite useful in environmental aquatic exposure assessments

Rogue wave generation by inelastic quasi-soliton collisions in optical fibres

Optical “rogue” waves are rare and very high intensity pulses of light that occur in optical devices such as communication fibers. They appear suddenly and can cause transmission errors and damage in optical communication systems. Indeed, the physics governing their dynamics is very similar to “monster” or “freak” waves on the Earth’s oceans, which are known to harm shipping. It is therefore important to characterize rogue wave generation, dynamics and, if possible, predictability. Here we demonstrate a simple cascade mechanism that drives the formation and emergence of rogue waves in the generalized non-linear Schrödinger equation with third-order dispersion. This generation mechanism is based on inelastic collisions of quasi-solitons and is well described by a resonant-like scattering behaviour for the energy transfer in pair-wise quasi-soliton collisions. Our theoretical and numerical results demonstrate a threshold for rogue wave emergence and the existence of a period of reduced amplitudes — a “calm before the storm” — preceding the arrival of a rogue wave event. Comparing with ultra-long time window simulations of 3.865 × 106ps we observe the statistics of rogue waves in optical fibres with an unprecedented level of detail and accuracy, unambiguously establishing the long-ranged character of the rogue wave power-distribution function over seven orders of magnitude

Cardiac assessment and inflammatory markers in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV2 (PIMS-TS) treated with methylprednisolone versus intravenous immunoglobulins: 6-month follow-up outcomes of the randomised controlled Swissped RECOVERY trial.

BACKGROUND: Previous findings from the Swissped RECOVERY trial showed that patients with Pediatric Inflammatory Multisystem Syndrome-Temporally Associated with SARS-CoV-2 (PIMS-TS) who were randomly assigned to intravenous immunoglobulins or methylprednisolone have a comparable length of hospital stay. Here, we report the 6-month follow-up outcomes of cardiac pathologies and normalisation of clinical or laboratory signs of inflammation from this study population. METHODS: This pre-planned follow-up of patients with PIMS-TS included the Swissped RECOVERY Trial reports on the 6-month outcomes of the cohort after randomisation, with a focus on cardiac, haematological, and biochemical findings. The trial was an investigator-initiated randomised multicentre open-label two-arm trial in children and adolescents hospitalised with PIMS-TS at ten hospitals in Switzerland. Cardiological assessments and laboratory analyses were prospectively collected in the intention-to-treat analysis on pre-defined intervals after hospital discharge. Differences between randomised arms were investigated using Chi-square test for categorical and Wilcoxon test for continuous variables. The trial is registered with the Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588). FINDINGS: Between May 21, 2021 and April 15, 2022, 75 patients with a median age of 9.1 years (IQR 6.2-12.2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulin group). During follow-up, the incidence of abnormal left ventricular systolic function, coronary artery aneurysms (CAA), and other signs of inflammation were comparable in both groups. However, we detected cardiac abnormalities with low incidence and a mild degree grade of pathology. CAAs were observed in 2/38 children (5.3%) in the IVIG group and 1/37 children (2.7%) in the methylprednisolone group at 6-month follow-up (difference proportion 0.75; 95% confidence interval (CI) -0.05 to 1.0; p = 0.39). INTERPRETATION: Methylprednisolone alone may be an acceptable first-line treatment as left ventricular systolic dysfunction and clinical/laboratory evidence for inflammation quickly resolved in all children. However, our findings need further confirmation through larger studies as our sample size is likely to be of insufficient power to address rare clinically relevant adverse outcomes. FUNDING: NOMIS, Vontobel, and Gaydoul Foundation

COVID-19 Vaccine Acceptance Among Parents of Children With Multisystem Inflammatory Syndrome in Children.

Data on COVID-19 vaccine acceptability among parents of children with multisystem inflammatory syndrome (MIS-C) are limited. In this cohort of children with MIS-C, enrolled in the Swissped RECOVERY trial (NCT04826588), comparing intravenous immunoglobulins or methylprednisolone, who, in accordance with Swiss guidelines, were recommended for SARS-CoV-2 vaccination, 65% (73/112) of parents reported being vaccinated against SARS-CoV-2 before the MIS-C, while 70% were vaccinated after the MIS-C episode of their child. None of the children were vaccinated before the occurrence of the MIS-C, and only 9% (5/56) received the COVID-19 vaccine after the MIS-C. The predominant barriers to COVID-19 vaccination were concerns over potential side effects and insufficient support from their doctors. This emphasizes the crucial role of health care providers in promoting COVID-19 vaccination among children