Catastrophic Reactions Research Articles

Living in LALA land? Forty years of attenuating Fc effector functions.

The Fc region of antibodies is vital for most of their physiological functions, many of which are engaged through binding to a range of Fc receptors. However, these same interactions are not always helpful or wanted when therapeutic antibodies are directed against self-antigens, and can sometimes cause catastrophic adverse reactions. Over the past 40 years, there have been intensive efforts to "silence" unwanted binding to Fc-gamma receptors, resulting in at least 45 different variants which have entered clinical trials. One of the best known is "LALA" (L234A/L235A). However, neither this, nor most of the other variants in clinical use are completely silenced, and in addition, the biophysical properties of many of them are compromised. I review the development of different variants to see what we can learn from their biological properties and use in the clinic. With the rise of powerful new uses of antibody therapy such as bispecific T-cell engagers, antibody-drug conjugates, and checkpoint inhibitors, it is increasingly important to optimize the Fc region as well as the antibody binding site in order to achieve the best combination of safety and efficacy.

Identification of Prodromal Parkinson Disease: We May Be Able to But Should We?

Parkinson disease (PD) remains a progressive and incurable disease. Research over the past decade provides strong evidence of a detectible phase before the clinical diagnosis, known as the prodromal phase of PD (pPD). In this article, we review the debate about disclosure of risk of progression to PD and related disorders to individuals through the perspectives of the pillars of medical ethics: beneficence, nonmaleficence, autonomy, and justice. There is evidence that lifestyle modification may have positive effects on onset and progression of PD, providing justification of potential benefit. From a societal perspective, a diagnosis of pPD could allow targeted recruitment to disease-modifying trials. Regarding nonmaleficence, direct evidence that catastrophic reactions are scarce is largely derived from studies of monogenic conditions, which may not be generalizable. Diagnosis of PD can be traumatic, and appropriate communication and evaluation of circumstances to weigh up disclosure is crucial. Future research should therefore examine the potential harms of early and of false-positive diagnoses and specifically examine these matters in diverse populations. Autonomy balances the right to know and the right not to know, so an individualized patient-centered approach and shared decision-making is essential, acknowledging that knowledge of being in the prodromal phase could prolong autonomy in the longer term. Distributive justice brings focus toward health care and related planning at the individual and societal level and affects the search for disease modification in PD. We must acknowledge that waiting for established disease states is likely to be too little, too late and results in failures of expensive trials and wasted participant and researcher effort. Ultimately, clinicians must arrive at a decision with the patient that solicits and integrates patients' goals, taking into account their individual life circumstances, perspectives, and philosophies, recognizing that one size cannot fit all.

Ultra-thin and Mechanically Stable LiCoO2-Electrolyte Interphase Enabled by Mg2+ Involved Electrolyte.

LiCoO2 (LCO) cathode materials have attracted significant attention for its potential to provide higher energy density in current Lithium-ion batteries (LIBs). However, the structure and performance degradation are exacerbated by increasing voltage due to the catastrophic reaction between the applied electrolyte and delithiated LCO. The present study focuses on the construction of physically and chemically robust Mg-integrated cathode-electrolyte interface (MCEI) to address this issue, by incorporating Magnesium bis(trifluoromethanesulfonyl)imide (Mg[TFSI]2) as an electrolyte additive. During formation cycles, the strong MCEI is formed and maintained its 2nm thickness throughout long-term cycling. Notably, Mg is detected not only in the robust MCEI, but also imbedded in the surface of the LCO lattice. As a result, the parasitic interfacial side reactions, surface phase reconstruction, particle cracking, Co dissolution and shuttling are considerably suppressed, resulting in long-term cycling stability of LCO up to 4.5V. Therefore, benefit from the double protection of the strong MCEI, the Li||LCO coin cell and the Ah-level Graphite||LCO pouch cell exhibit high capacity retention by using Mg-electrolyte, which are 88.13% after 200 cycles and 90.4% after 300 cycles, respectively. This work provides a novel approach for the rational design of traditional electrolyte additives.

How to get over with medication errors underestimation? Improving indices of medication errors with focus on intravenous medications in hematopoietic stem cell transplantation setting; a direct observation study.

The administration of intravenous (IV) medications is a technically complicated and error-prone process. Especially, in the hematopoietic stem cell transplantation (HSCT) setting where toxic drugs are frequently used and patients are in critical immunocompromised conditions, medication errors (ME) can have catastrophic reactions and devastating outcomes such as death. Studies on ME are challenging due to poor methodological approaches and complicated interpretations. Here, we tried to resolve this problem using reliable methods and by defining new denominators, as a crucial part of an epidemiological approach. This was an observational, cross-sectional study. A total of 525 episodes of IV medication administration were reviewed by a pharmacist using the disguised direct observation method to evaluate the preparation and administration processes of 32 IV medications in three HSCT wards. We reported errors in 3 ratios; 1) Total Opportunities for Error (TOE; the number of errors/sum of all administered doses observed plus omitted medications), 2) Proportional Error Ratio (the number of errors for each drug or situation/total number of detected errors) and, 3) Corrected Total Opportunities for Errors (CTOE; the number of errors/ Sum of Potential Errors (SPE)). A total of 1,568 errors were observed out of 5,347 total potential errors. TOE was calculated as 2.98 or 298% and CTOE as 29.3%. Most of the errors occurred at the administration step. The most common potential errors were the use of an incorrect volume of the reconstitution solvent during medication preparation and lack of monitoring in the administration stage. Medication errors frequently occur during the preparation and administration of IV medications in the HSCT setting. Using precise detection methods, denominators, and checklists, we identified the most error-prone steps during this process, for which there is an urgent need to implement effective preventive measures. Our findings can help plan targeted preventive measures and investigate their effectiveness, specifically in HSCT settings.

Cold Urticaria: An Under-recognised Cause of Perioperative Anaphylaxis

Anaphylaxis is a rare but severe, potentially life threatening allergic reaction which commonly presents with cutaneous to multisystem involvement. The overall incidence rate of anaphylaxis during general anaesthesia varies greatly, ranging from 1:20,000 to 1:38. Cold urticaria, subset of chronic urticaria, is characterised with the presence of localised wheals to systemic and anaphylactic reactions. Physical urticaria can be due to physical stimuli such as friction, pressure, sun exposure and cold. Cold urticaria mainly comprises of physical urticaria rather which ranges from 3-33.8% with a higher incidence in cold climate. A case of physical cold urticaria was reported during perioperative period in a 40-year-old male who was posted in urology OT for a planned Ureteroscopy (URS). On pre-anaesthetic evaluation, patient’s medical, surgical and personal history found to be inconclusive. Patient was fit for surgery under ASA grade 1 and advised to be kept nil per orally for six hours for solid food and two hours for clear fluid. At the conclusion of surgery, patient developed shivering and was managed with warm blankets and radiant heater. After some time, patient develop wheals over chest, abdomen and lower back. Patient was managed with warm fluids, warming the patient, maintaining ambient OT temperature and drugs like injection pheniramine, epinephrine and dexamethasone to prevent catastrophic reaction. Through evaluation during preoperative period plays a key role in anticipation of these kind of untoward events. This case report describes the occurrence and management of this rare condition.

Boosting the Intrinsic Stability of Lithium Metal Anodes by an Electrochemically Active Encapsulating Framework

AbstractThe lithium metal anode (LMA) is a promising technology to promote the energy density of secondary batteries. However, the coupled growth of surface corrosion and deposited lithium with high reactivity causes capacity fading and safety hazards, especially at high temperatures. Great efforts have been focused on preventing the LMA from direct contact with electrolytes to extend its lifespan, but few pay attention to its stability at high temperatures, which is crucial to battery safety. Herein, a 3D Li22Sn5‐based interpenetrated skeleton is introduced into the bulk of LMA with mechanical kneading, which enables a LMA with fast and stable cycles at high temperatures and improved safety under thermal abuse. The Li22Sn5 skeleton acts as a solid electrolyte inside the bulk, allowing rapid Li+ ion transport and homogenous lithium stripping/plating into the porous bulk through Li/Li22Sn5 interface. The encapsulating framework expands the electrochemically active area and limits its exposure to the electrolyte, enabling a LMA with steady cyclability even at 60 °C. Trapping lithium inside the thermally stable skeleton postpones the catastrophic exothermal reactions between lithium and electrolytes. The strategy for constructing a 3D encapsulating lithiophilic framework is promising for creating safe and stable lithium metal batteries working under harsh circumstances.

Vaccine-induced immune thrombotic thrombocytopenia: what do we know hitherto?

Vaccine-induced immune thrombotic thrombocytopenia (VITT), also known as thrombosis with thrombocytopenia syndrome, is a catastrophic and life-threatening reaction to coronavirus disease 2019 (COVID-19) vaccines, which occurs disproportionately in response to vaccination with non-replicating adenovirus vector (AV) vaccines. The mechanism of VITT is not well defined and it has not been resolved why cases of VITT are predominated by vaccination with AV vaccines. However, virtually all VITT patients have positive platelet-activating anti-platelet factor 4 (PF4) antibody titers. Subsequently, platelets are activated and depleted in an Fcγ-receptor IIa (FcγRIIa or CD32a)-dependent manner, but it is not clear why or how the anti-PF4 response is mounted. This review describes the pathogenesis of VITT and provides insight into possible mechanisms that prompt the formation of a PF4/polyanion complex, which drives VITT pathology, as an amalgam of current experimental data or hypotheses.

Goldstein's 'catastrophic reactions' reinterpreted as neuroaesthetic 'signatures': Comment on "Can we really 'read' art to see the changing brain? A review and empirical assessment of clinical case reports and published artworks for systematic evidence of quality and style changes linked to damage or neurodegenerative disease" by Matthew Pelowski et al.

Goldstein's 'catastrophic reactions' reinterpreted as neuroaesthetic 'signatures': Comment on "Can we really 'read' art to see the changing brain? A review and empirical assessment of clinical case reports and published artworks for systematic evidence of quality and style changes linked to damage or neurodegenerative disease" by Matthew Pelowski et al.

Emotional disorders after stroke

Emotional disorders are common among patients after stroke. They include anger, fear, emotional expression control (uncontrollable crying, laughing), emotional indifference (apathy), disorders of emotion recognition and emotional empathy. They might develop independently or as a presentation of depression, anxiety, catastrophic reaction, posttraumatic stress disorder etc. Treatment of post-stroke emotional disorders include pharmacotherapy, psychotherapy, neuromodulation.

Innovative Accident Tolerant Fuel Materials May Help Extending the Life of Light Water Reactors: A Perspective

One of the main sources of clean electricity in the civilian power grid comes from light water reactors (LWRs). Some of these LWRs are being decommissioned prematurely because they may not be economically sustainable. It is proposed that the use of accident-tolerant fuel concepts may enable for LWR plant operation extension by making them safer and more economically competitive to operate. For example, the use of iron-chromium-aluminum (FeCrAl) alloys for the cladding of the fuel would not only reduce the risk of catastrophic reaction between the cladding and its environment in the case of a loss of coolant accident situation but also, for example, allow for higher fuel burnup during normal plant operation.

An improved pillar design methodology

Empirical pillar design methods are commonly used in the mining industry. The parameters within which these methods are valid are frequently unknown to the user or ignored. In addition, empirical design may not consider essential parameters such as blasting effects, orebody dip and the presence of geological structures, which all adversely affect the stability of the pillars. This can result in potentially serious pillar design strength over-estimates. Although the commonly based tributary area method is generally conservative, as the spans are seldom that large relative to the depth, failing to consider other relevant parameters can result in errors. Problems associated with an under-designed pillar can range from a local pillar collapse to a catastrophic chain reaction collapse (or run). Over-designed pillars are generally safe but reduce the extraction of the orebody, thus adversely affecting the profitability of the mining operation. We used laboratory tests and numerical modelling to understand the effects of pillar orientation, blasting and the presence of discontinuities on pillar strength. Reduction factors were developed with these models to be implemented in conjunction with the existing empirical pillar design methods. For any pillar or mine design, once it is implemented, the actual performance of the system must be checked regularly by observation and monitoring and adjusted if needed. The pillar design approach outlined in this paper can better optimize the pillar mining method by considering other generally ignored but important parameters, thus improving safety, productivity, and economic aspects.

Evaluation of progressive collapse behavior in reinforced concrete buildings

Progressive collapse is a catastrophic chain reaction of failure of a structure that is caused due to loss of vertical load bearing element of the structure, resulting damage of a part of the structure or entire structure. In our research work 10 storey regular Reinforced Concrete framed structure is considered and is seismically designed with IS 1893:2016 in SAP2000 version 20 modeling. The different column removal scenarios both in plan and elevation suggested by guidelines were examined by alternate load path method using nonlinear staged construction available in the software and then identify the potential of the structure to withstand progressive collapse. Numerical results were compared by analyzing columns and beams separately by calculating demand capacity ratios and the requirement of percentage of steel for failed structural elements are predicted both in flexure and shear stresses. Our objective is to provide clear conceptual step-by-step descriptions of various procedures for progressive collapse analysis 3D (three-dimensional) Finite Element Methods (FEM) and non-linear static push-down analysis in SAP2000 software was used to assess the progressive collapse potential of a typical gravity-load designed mid-rise reinforced concrete building with open ground floor. The beam is actually designed to resist the shear force up to 39.84 kN. So in order to resist the shear failure we need to provide enough vertical reinforcement. The failed structural elements were re-designed to resist progressive collapse in order to satisfy the acceptance criteria recommended by the guidelines. It’s showed that the incorporation of perimeter beams in buildings improved the progressive collapse resistance as it reduces joint displacement and chord rotation at column removal locations by providing sufficient stiffness and load paths for increased gravity loads. The study results can be used to develop and calibrate the nonlinear numerical model for analyzing high-rise building progressive collapse behavior and can help provide information that may improve new and existing reinforced concrete core-wall building robustness against progressive collapse.

STUDY OF PROGRESSIVE COLLAPSE ON MULTI-STORIED STEEL STRUCTURE

Progressive collapse is a catastrophic chain reaction of failure initiated by loss of vertical bearing load element of the structure resulting in damage of a part of the structure or entire structure. In the current study, it is intended to investigate the progressive collapse potential of multi-storied steel structure according to IS 1893:2002. The buildings include regular and irregular plans of total 5 models with column removed at three different locations at first storey in order to study consequences and check safety of adjacent members. Pushover Analysis is also conducted for all the models. The seismic response of steel structure in terms of performance point and the effect of earthquake forces on multi storey building with the help of pushover analysis is carried out in this paper. Modelling and Analysis of the buildings are performed using ETABS 2017. Key Words: Progressive collapse, DCR ratio, Pushover Analysis, Performance point, Hinge Formation

Chronic Tinnitus and the Positive Effects of Sound Treatment via a Smartphone App: Mixed-Design Study.

BackgroundTinnitus is a phantom auditory sensation in the absence of an external stimulus. It is accompanied by a broad range of negative emotional symptoms and a significantly lower quality of life. So far, there is no cure for tinnitus, although various treatment options have been tried. One of them is mobile technology employing dedicated apps based on sound therapy. The apps can be managed by the patient and tailored according to their needs.ObjectiveThe study aims to assess the effect of a mobile app that generates background sounds on the severity of tinnitus.MethodsThe study involved 68 adults who had chronic tinnitus. Participants were divided into a study group (44 patients) and a control group (24 patients). For 6 months those in the study group used a free mobile app that enriched the sound environment with a background sound. Participants were instructed to use the app for at least 30 minutes a day using their preferred sound. The participants in the control group did not use the app. Subjective changes in the day-to-day functioning of both groups were evaluated using the Tinnitus Handicap Inventory (THI) questionnaire, a visual analog scale, and a user survey.ResultsAfter 3 months of using the app, the THI global score significantly decreased (P<.001) in the study group, decreasing again at 6 months (P<.001). The largest improvements were observed in the emotional and catastrophic reactions subscales. A clinically important change in the THI was reported by 39% of the study group (17/44). Almost 90% of the study participants (39/44) chose environmental sounds to listen to, the most popular being rain and ocean waves. In the control group, tinnitus severity did not change over 3 or 6 months.ConclusionsAlthough the participants still experienced limitations caused by tinnitus, the advantage of the app was that it led to lower negative emotions and thus reduced overall tinnitus severity. It is worth considering whether a mobile app might be incorporated into the management of tinnitus in a professional setting.

Indigo Carmine Hemodynamic Studies to Treat Vasoplegia Induced by Compound 48/80 in a Swine Model of Anaphylaxis.

IntroductionThere are many reasons to believe that the nitric oxide/guanosine 3’5’ - cyclic monophosphate (or NO/cGMP) pathway on vasoplegic states is underestimated. To study indigo carmine (IC) as an alternative to methylene blue was the investigation rationale.MethodsThe IC (3mg/kg intravenous infusion) study protocol included five experimental groups; 1) Control group — saline was injected at 0 and 10 minutes; 2) IC group — IC was injected at 0 and saline at 10 minutes; 3) compound 48/80 (C48/80) group — C48/80 was injected at 0 minute and saline at 10 minutes; 4) C48/80 + IC group — C48/80 was injected at 0 minute and IC at 10 minutes; and 5) IC + C48/80 group — IC was injected at 0 minute and C48/80 at 10 minutes. The studies were carried out by registering and measuring hemodynamic and blood gasometric parameters, including continuous cardiac output.Results1) The effects of the drugs (IC and C48/80) were more evident in the first 20 minutes of recording; 2) hypotensive responses were more pronounced in the C48/80 groups; 3) IC isolated or applied before C48/80 caused transient pulmonary hypertension; and 4) after the first 20 minutes, the pressure responses showed stability with apparent hypotension more pronounced in the C48/80 groups. Clinical observations showed significant hemodynamic instability and catastrophic anaphylactic reactions (agitation, pulmonary hypertension, severe bronchospasm, urticaria, high-intensity cyanosis, violent gastric hypersecretion, and ascites).ConclusionA global results analysis showed differences between groups only in the first 20 minutes of the experiments.

Aortic homograft for aortic valve replacement in patient with Alpha-Gal allergy.

Allergy to Galactose-Alpha-1,3-Galactose is an allergy to mammalian proteins, that are present on the surface of standard bioprosthestic valves, and could result in a catastrophic allergic reaction or may cause early deterioration of the bioprostheses. Aortic homograft is an acceptable alternative to standard prosthetic valves (biological and mechanical) to avoid a potential allergic manifestation and the need for definitive oral anticoagulation. We report the implantation of an aortic homograft in a patient with an aortic stenosis who presents a documented AlphaGal allergy.

Dysregulation, Catastrophic Reactions, and the Anxiety Disorders.

Normal developmental activities (eg, going to school, raising a hand in class, and managing typical life uncertainties) are 'triggers' for children and adolescents with anxiety disorders. To cope, children with anxiety avoid; however, when avoidance of developmentally appropriate activities is not possible, catastrophic responses can ensue. If these catastrophic reactions result in successful avoidance, they are likely to recur leading to a generalized pattern of dysregulated behavior. Interventions include treating anxiety disorder symptoms to remission. For parents the goal is to challenge their child to engage in important developmental activities, reward positive coping and avoid reinforcing avoidance behavior.

Tensegrity Metamaterials: Tensegrity Metamaterials: Toward Failure‐Resistant Engineering Systems through Delocalized Deformation (Adv. Mater. 10/2021)

Failure of materials and structures is the inevitable consequence of a catastrophic chain reaction of locally confined damage events. Breaking with this paradigm, in article number 2005647, Julian J. Rimoli, Lorenzo Valdevit, and co-workers introduce a novel class of tensegrity metamaterials. By connecting isolated loops of compressive elements through a continuous tension network, these metamaterials delocalize deformation, demonstrating a pathway toward superior failure-resistant engineering systems.

Chapter 7 - Hemispheric stroke: Mood disorders

Stroke causes many forms of disability, including emotional and mood disorders. Depression is the most common of these, affecting approximately one-third of stroke patients. Other disorders like mania, bipolar disorder, anxiety disorder, or apathy may also develop following stroke, although they are less common. The development of mood and emotional disorders is dependent on the severity of brain injury, the side of injury, and hemispheric location. Whereas a left hemispheric stroke often results in depression or a catastrophic reaction with anxiety, injury to the right hemisphere has predominantly been associated with the development of emotional indifference (anosodiaphoria) or euphoria. In this chapter, we discuss the mood disorders associated with hemispheric strokes and the neuropsychological mechanisms that might account for the clinical manifestations of these affective disorders.

Genetic counselling and testing for inherited dementia: single-centre evaluation of the consensus Italian DIAfN protocol

BackgroundA consensus protocol for genetic counselling and testing of familial dementia, the Italian Dominantly Inherited Alzheimer’s and Frontotemporal Network (IT-DIAfN) protocol, has been developed in Italy by a network of expert dementia centres. The aim of this study is to evaluate feasibility and acceptability of the genetic counselling and testing process, as undertaken according to the IT-DIAfN protocol in one of the IT-DIAfN dementia research centres.MethodsThe protocol was tested by a multidisciplinary team at the IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy, on affected individuals with suspected inherited forms of Alzheimer’s disease (AD) or frontotemporal dementia (FTD), and to healthy at-risk relatives. The genetic counselling and testing process consisted of (i) pre-test consultation and psychological assessment (ii) genetic testing, (iii) genetic test result disclosure and (iv) follow-up consultation and psychological assessment.ResultsTwenty affected individuals from 17 families fulfilled the family history criteria of the IT-DIAfN protocol for suspected inherited dementia (17 for AD, 2 for FTD, 1 for inclusion body myopathy with Paget disease of bone and frontotemporal dementia) and were included in the protocol. Nineteen out of 20 affected individuals received the genetic test result (one left after the pre-test consultation being not ready to cope with an unfavourable outcome). A pathogenic mutation was found in 6 affected individuals (1 in PSEN1, 2 in PSEN2, 1 in GRN, 1 in MAPT, 1 in VCP). Eleven healthy at-risk relatives asked to undergo predictive testing and were included in the protocol. Three completed the protocol, including follow-up; one did not ask for the genetic test result after genetic testing; and eight withdrew before the genetic testing, mainly due to an increased awareness about the possible consequences of an unfavourable test result. To date, no catastrophic reactions were reported at the follow-up.ConclusionsOur case series shows that a structured genetic counselling and testing protocol for inherited dementia can be implemented in both affected individuals and at-risk relatives in a research setting. The procedure was shown to be safe in terms of occurrence of catastrophic events. A formal validation in larger cohorts is needed.