Reversible Events Research Articles

Wearable chest sensor for stride and respiration detection during running

Endurance running is among the most popular physical activities partially due to its low barriers to entry. However, some people avoid running because of respiratory distress, and respiratory monitoring could help prevent this. Wearable sensors are valuable for respiration detection during exercise and enable respiratory feedback in real time. Therefore, this study presents a wearable chest-mounted stride and respiration sensor including step and flow reversal event detection algorithms. The algorithms were evaluated using precision and recall between detected and reference events with respect to different levels of breathing depth, motion artifact, thoracic skin temperature and sweat. Overall F1 scores reached 93.2%, 97.4% and 97.2% for step, expiration and inspiration events, respectively. No significant effect on event detection performance was observed for breathing depth, stride motion artifact, or thoracic skin temperature. In contrast, sweat level slightly decreased detection performance. Consequently, this sensor is able to accurately measure stride and respiration during running and could be suitable for use as a system to guide runners’ respiration during exercise.

Neurologic outcome following liver transplantation for methylmalonic aciduria.

Liver and liver/kidney transplantation are increasingly used in methylmalonic aciduria, but little is known on their impact on CNS. The effect of transplantation on neurological outcome was prospectively assessed in six patients pre- and post-transplant by clinical evaluation and by measuring disease biomarkers in plasma and CSF, in combination with psychometric tests and brain MRI studies. Primary (methylmalonic- and methylcitric acid) and secondary biomarkers (glycine and glutamine) significantly improved in plasma, while they remained unchanged in CSF. Differently, biomarkers of mitochondrial dysfunction (lactate, alanine, and related ratios) significantly decreased in CSF. Neurocognitive evaluation documented significant higher post-transplant developmental/cognitive scores and maturation of executive functions corresponding to improvement of brain atrophy, cortical thickness, and white matter maturation indexes at MRI. Three patients presented post-transplantation reversible neurological events, which were differentiated, by means of biochemical and neuroradiological evaluations, into calcineurin inhibitor-induced neurotoxicity and metabolic stroke-like episode. Our study shows that transplantation has a beneficial impact on neurological outcome in methylmalonic aciduria. Early transplantation is recommended due to the high risk of long-term complications, high disease burden, and low quality of life.

The 80th Anniversary of Cortical Spreading Depression of Leao: A Major Component in Experimental and Clinical Neuropathology

Understanding of the mechanisms behind brain neuropathology is a major factor in diagnosis as well as treatment of patients. The discovery of the reversible event of cortical spreading depression (CSD) in conjunction with epileptic activity led a new era in better understanding of brain pathology. Eighty years ago, A.A.P. Leao discovered this unique response, of the cerebral cortex of animals, to mechanical, chemical or electrical stimulation. A single CSD wave that propagate in the rate of 3-6 mm/minute includes electrical, ionic, circulatory and metabolic responses. The metabolic changes include activation of oxygen consumption as evaluated by monitoring of mitochondrial NADH redox state. It was found that CSD could be developed spontaneously after various perturbations such as moderate hypoxia or ischemia, epileptic activity, hyperbaric oxygenation, head injury and brain retraction. Our conclusion is that better clinical monitoring of the brain that will detect the appearance of CSD will improve patient’s care in critical situations.

Reiterative Code-Switching: Argument-Marking in Cena

Situations of language contact are often the norm for sign languages. This article investigates a case of unimodal contact between Cena, a young sign language in its third generation that is used in a small rural community in Brazil, and Libras, the national sign language of Brazil. Our analysis concerns one by-product of this contact: reiterative code-switches, wherein signers produce a sequence of two signs—one from each language—with the same meaning to label a single referent. We consider several motivations detailed in existing literature on code-switching, before proposing an explanation motivated by the disambiguation of reversible (therefore potentially ambiguous) verb events, primarily by using reiteration to focus agents. We suggest that with this phenomenon, we see signers employ a previously unattested strategy to mark arguments and thereby aid syntactic disambiguation.

Defective excitation-contraction coupling and mitochondrial respiration precede mitochondrial Ca2+ accumulation in spinobulbar muscular atrophy skeletal muscle

Polyglutamine expansion in the androgen receptor (AR) causes spinobulbar muscular atrophy (SBMA). Skeletal muscle is a primary site of toxicity; however, the current understanding of the early pathological processes that occur and how they unfold during disease progression remains limited. Using transgenic and knock-in mice and patient-derived muscle biopsies, we show that SBMA mice in the presymptomatic stage develop a respiratory defect matching defective expression of genes involved in excitation-contraction coupling (ECC), altered contraction dynamics, and increased fatigue. These processes are followed by stimulus-dependent accumulation of calcium into mitochondria and structural disorganization of the muscle triads. Deregulation of expression of ECC genes is concomitant with sexual maturity and androgen raise in the serum. Consistent with the androgen-dependent nature of these alterations, surgical castration and AR silencing alleviate the early and late pathological processes. These observations show that ECC deregulation and defective mitochondrial respiration are early but reversible events followed by altered muscle force, calcium dyshomeostasis, and dismantling of triad structure.

On multistability and constitutive relations of cell motion on fibronectin lanes

Cell motility on flat substrates exhibits coexisting steady and oscillatory morphodynamics, the biphasic adhesion-velocity relation, and the universal correlation between speed and persistence (UCSP) as simultaneous observations common to many cell types. Their universality and concurrency suggest a unifying mechanism causing all three of them. Stick-slip models for cells on one-dimensional lanes suggest multistability to arise from the nonlinear friction of retrograde flow. This study suggests a mechanical mechanism controlled by integrin signaling on the basis of a biophysical model and analysis of trajectories of MDA-MB-231 cells on fibronectin lanes, which additionally explains the constitutive relations. The experiments exhibit cells with steady or oscillatory morphodynamics and either spread or moving with spontaneous transitions between the dynamic regimes, spread and moving, and spontaneous direction reversals. Our biophysical model is based on the force balance at the protrusion edge, the noisy clutch of retrograde flow, and a response function of friction and membrane drag to integrin signaling. The theory reproduces the experimentally observed cell states, characteristics of oscillations, and state probabilities. Analysis of experiments with the biophysical model establishes a stick-slip oscillation mechanism, and explains multistability of cell states and the statistics of state transitions. It suggests protrusion competition to cause direction reversal events, the statistics of which explain the UCSP. The effect of integrin signaling on drag and friction explains the adhesion-velocity relation and cell behavior at fibronectin density steps. The dynamics of our mechanism are nonlinear flow mechanics driven by F-actin polymerization and shaped by the noisy clutch of retrograde flow friction, protrusion competition via membrane tension, and drag forces. Integrin signaling controls the parameters of the mechanical system.

Stress Features Inferred From Induced Earthquakes in the Weiyuan Shale Gas Block in Southwestern China

AbstractStress features, particularly local stress field and earthquake stress drops, are important to understand mechanism of induced earthquakes. Since shale gas exploitations in 2015, the Weiyuan shale gas block has experienced frequent earthquakes. In this paper, we determine focal mechanisms of 257 events with ML > 1.5 by fitting three‐component waveforms, invert for direction of maximum horizontal stress for two dense earthquake clusters, and then calculate stress drops for 17 earthquakes with moment magnitudes between 2.2 and 2.75 through the spectral ratio method. The focal mechanisms of all earthquakes are reverse faulting. The orientation of local maximum horizontal compressive stress is in the ESE direction, consistent with crustal movement indicated by GPS measurements. Both the focal mechanisms and microseismicity locations suggest the existence of steeply dipping faults with dip angles of ∼70°, which are relatively rare and difficult to slip under usual conditions, unlike major induced earthquakes with strike‐slip or low‐angle thrusting faults in the midwestern United States and western Canada. However, the steeply dipping reverse events can be induced by large pore pressure from hydraulic fracturing. The stress drops range from 2.5 to 54.7 MPa, comparable to those of potentially induced earthquakes in the midwestern United States. Our results imply earthquakes in the Weiyuan area are controlled by local tectonic stress and induced by large pore pressure from hydraulic fracturing, which advances our knowledge of reactivation of steeply dipping reverse faults.

On multistability and constitutive relations of cell motion on fibronectin lanes.

Cell motility on flat substrates exhibits multistability between steady and oscillatory morphodynamics, spread and moving states, the biphasic adhesion-velocity relation, and the universal correlation between speed and persistence (UCSP) as simultaneously observed phenomena. Their universality and concurrency suggest a unifying mechanism to exist causing all of them. We search for that mechanism by investigating trajectories of MDA-MB-231 cells on Fibronectin lanes. We also find multistability caused by the clutch mechanism of retrograde flow. Control of the clutch parameters by integrin signalling causes the biphasic adhesion-velocity relation. Protrusion competition based on the clutch causes direction reversal events, the statistics of which explains the UCSP. We suggest that F-actin polymerisation, the clutch mechanism of retrograde flow, protrusion competition via membrane tension and drag forces cause the multistability and dynamic cell states, state transition statistics causes the UCSP and the control of this dynamic system by integrin signalling entails the adhesion-velocity relation.

Research of Seismogenic Structures of the 2016 and 2022 Menyuan Earthquakes, in the Northeastern Tibetan Plateau

On 8 January 2022, a Moment Magnitude (Mw) 6.7 earthquake occurred in Menyuan, China. The epicenter was located in the western segment of the Lenglongling fault of the Qilian-Haiyuan fault zone. In this area, the Mw 5.9 Menyuan earthquake on 26 August 1986 and the Mw 5.9 Menyuan earthquake on 21 January 2016 successively occurred. The seismogenic structures of the 1986 and 2016 earthquakes are on the Northern Lenglongling fault, which is a few kilometers away from the Lenglongling fault. After the 2022 Menyuan earthquake, we collected GF-7 and Sentinel-1 satellite images to measure the surface deformation of the earthquake sequence. Based on the elastic dislocation theory, the fault model and fault slip distribution of the 2016 and 2022 Mengyuan earthquakes were inverted using coseismic surface displacements. The results show that the 2016 event is a reverse event, with the maximum coseismic surface displacement on LOS reaching 8 cm. The strike, dip, and rake of the earthquake rupture were 139°, 41°, and 78°, with the maximum slip reaching 0.6 m at a depth of 8 km. The surface rupture of the 2022 Mw 6.7 earthquake ran in the WNW–ESE direction with a maximum displacement on LOS of 72 cm. The main seismogenic fault of the 2022 event was the western segment of the Lenglongling fault. The strike, dip, and rake of the rupture were 112°, 85°, and 3°, with the maximum slip reaching 4 m at a depth of 4 km. The Coulomb failure stress change shows that the earthquake sequence generated a considerable positive Coulomb failure stress of more than 2 bar. These observations suggest that the earthquake sequence around Menyuan is mainly governed by the activities of the Lenglongling fault around the northeastern Tibetan Plateau. In addition, their sequential occurrences could be related to earthquake-triggering mechanisms due to stress interaction on different deforming faults. Thus, the Lenglongling fault has received a great amount of attention regarding its potential earthquake hazards.

Can metallic bipolar plates with low-cost Cr/a-C coating withstand cell reversal events in PEMFCs? Post-coated vs pre-coated BPs

The so-called cell reversal caused by H2 starvation during polymer electrolyte membrane fuel cell operation can lead to anode potentials >1.5 Vanode and thus to significant carbon corrosion in the anode catalyst layer. In this work, the influence of cell reversals on the electrochemical stability of low-cost Cr/a-C post- and pre-coating on metallic bipolar plates (BPs) was investigated in a vehicle application-oriented test cycle. While the electrical resistance of the BPs with the low-cost coatings increased after the tests, no impact on the H2/air polarization curves was detected in comparison to BPs coated with Au as reference. Nevertheless, surface changes of the carbon coatings were detected in regions of BP bends because of water accumulation. Further analyses showed that corrosion products from the chromium interlayer were detected. We therefore assume that the high electrochemical potential during the cell reversal events can only corrode the low-cost carbon coatings on the BP in the presence of water, while the overall degradation of the BPs regarding their electrical resistance was negligible compared to the performance loss due to anode catalyst layer corrosion. Furthermore, no significant difference of the degradation characteristics (metal ion leaching, anode catalyst layer thinning) was found regarding the coating sequence.

Acceptability and feasibility of a planned preconception weight loss intervention in women with long-acting reversible contraception: the Plan-it mixed-methods study

Women with overweight (a body mass index of ≥ 25 kg/m2) or obesity (a body mass index of ≥ 30 kg/m2) are at greater risk of experiencing complications during pregnancy and labour than women with a healthy weight. Women who remove their long-acting reversible contraception (i.e. coils or implants) are one of the few groups of people who contact services as part of their preparation for conception, creating an opportunity to offer a weight loss intervention. The objectives were to understand if routine NHS data captured the pathway from long-acting reversible contraception removal to pregnancy and included body mass index; to identify the suitable components of a preconception weight loss intervention; and to engage with key stakeholders to determine the acceptability and feasibility of asking women with overweight/obesity to delay the removal of their long-acting reversible contraception in order to take part in a preconception weight loss intervention. This was a preparatory mixed-methods study, assessing the acceptability and feasibility of a potential intervention, using routine NHS data and purposefully collected qualitative data. The NHS routine data included all women with a long-acting reversible contraception code. There were three groups of participants in the surveys and interviews: health-care practitioners who remove long-acting reversible contraception; weight management consultants; and women of reproductive age with experience of overweight/obesity and of using long-acting reversible contraception. UK-based health-care practitioners recruited at professional meetings; and weight management consultants and contraceptive users recruited via social media. Anonymised routine data from UK sexual health clinics and the Clinical Practice Research Datalink, including the Pregnancy Register; and online surveys and qualitative interviews with stakeholders. The records of 2,632,871 women aged 16-48 years showed that 318,040 had at least one long-acting reversible contraception event, with 62% of records including a body mass index. Given the identified limitations of the routine NHS data sets, it would not be feasible to reliably identify women with overweight/obesity who request a long-acting reversible contraception removal with an intention to become pregnant. Online surveys were completed by 100 health-care practitioners, four weight management consultants and 243 contraceptive users. Ten health-care practitioners and 20 long-acting reversible contraception users completed qualitative interviews. A realist-informed approach generated a hypothesised programme theory. The combination of weight discussions and the delay of long-acting reversible contraception removal was unacceptable as an intervention to contraceptive users for ethical and practical reasons. However, a preconception health intervention incorporating weight loss could be acceptable, and one potential programme is outlined. There was very limited engagement with weight management consultants, and the sample of participating stakeholders may not be representative. An intervention that asks women to delay long-acting reversible contraception removal to participate in a preconception weight loss intervention would be neither feasible nor acceptable. A preconception health programme, including weight management, would be welcomed but requires risk communication training of health-care practitioners. Work to improve routine data sets, increase awareness of the importance of preconception health and overcome health-care practitioner barriers to discussing weight as part of preconception care is a priority. This trial is registered as ISRCTN14733020. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 1.

Event Feature Pre-training Model Based on Public Opinion Evolution

The comments in the evolution of network public opinion events not only reflect the attitude of netizens towards the event itself, but also are the key basis for mastering the dynamics of public opinion. According to the comment data in the event evolution process, an event feature vector pre-training model NL2ER-Transformer is constructed to realize the real-time automatic extraction of event features. Firstly, a semi-supervised multi-label curriculum learning model is proposed to generate comment words, event word vectors, event words, and event sentences, so that a public opinion event is mapped into a sequence similar to vectorized natural language. Secondly, based on the Transformer structure, a training method is proposed to simulate the evolution process of events, so that the event vector generation model can learn the evolution law and the characteristics of reversal events. Finally, the event vectors generated by the presented NL2ER-Transformer model are compared with the event vectors generated by the current mainstream models such as XLNet and RoBerta. This paper tests the pre-trained model NL2ER-Transformer and three pre-trained benchmark models on four downstream classification models. The experimental results show that using the vectors generated by NL2ER-Transformer to train downstream models compared to using the vectors generated by other pre-trained benchmark models to train downstream models, the accuracy, recall, and F1 values are 16.66%, 44.44%, and 19% higher than the best downstream model. At the same time, in the evolutionary capability analysis test, only four events show partial errors. In terms of performance of semi-supervised model, the proposed semi-supervised multi-label curriculum learning model outperforms mainstream models in four indicators by 6%, 23%, 8%, and 15%, respectively.

A Reversible Event Leading to Lifestyle Reversion: About a Case of PRES

The posterior reversible encephalopathy syndrome (PRES) is a heterogeneous clinical-radiological characterized by a combination of encephalopathy, altered mental status, epileptic seizures, visual disturbances, headache, and focal neurologic signs. Other neurologic deficits, such as ataxia, may occur. PRES can be found in a nonposterior distribution, mainly in watershed areas, including the frontal, inferior temporal, cerebellar, and brainstem regions. We present the case of a middle age male presenting with headache, dizziness, ataxia, and hypertensive emergency. PRES was suspected, and the diagnosis was confirmed by brain magnetic resonance imaging. Computerized tomography showed bilateral hypodensities of the cerebellar white matter with associated narrowing of the cortical sulci and basal cisterns. This case represents a rare presentation of PRES with unusual clinical and topographical involvement, such as brainstem and cerebellum.

Back to restitutive readings again

This paper observes that adverbs meaning ‘back’ systematically give rise to restitutive readings which have long been thought of only as secondary readings of adverbs meaning ‘again’. Restitutive readings are argued to arise from two sources: repetition of a state, or reversal of an event. Languages like English and Hindi-Urdu have a separate dedicated adverb for each, showing the independence of these two sources. A single reversal-based/counterdirectional lexical entry (originally proposed for AGAIN) is demonstrated to capture an intuitive relationship that exists between three core readings of BACK. These readings are, however, shown to have several as yet unconsidered properties that necessitate a finer-grained expression of counterdirectionality than is afforded by the broad concept of reverse events. The paper significantly revises the counterdirectional presupposition, capturing the core readings of BACK-adverbs by appealing not to repetition or reversal but to elements that can be copied from the assertion itself: THEME, SCALE, and end point of scalar change.

Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C

BackgroundAdagrasib, an oral small-molecule inhibitor of mutant KRAS G12C protein, has shown clinical activity in pretreated patients with several tumor types, including colorectal cancer. Preclinical studies suggest that combining a KRAS G12C inhibitor with an epidermal growth factor receptor antibody could be an effective clinical strategy.MethodsIn this phase 1–2, open-label, nonrandomized clinical trial, we assigned heavily pretreated patients with metastatic colorectal cancer with mutant KRAS G12C to receive adagrasib monotherapy (600 mg orally twice daily) or adagrasib (at the same dose) in combination with intravenous cetuximab once a week (with an initial loading dose of 400 mg per square meter of body-surface area, followed by a dose of 250 mg per square meter) or every 2 weeks (with a dose of 500 mg per square meter). The primary end points were objective response (complete or partial response) and safety.ResultsAs of June 16, 2022, a total of 44 patients had received adagrasib, and 32 had received combination therapy with adagrasib and cetuximab, with a median follow-up of 20.1 months and 17.5 months, respectively. In the monotherapy group (43 evaluable patients), a response was reported in 19% of the patients (95% confidence interval [CI], 8 to 33). The median response duration was 4.3 months (95% CI, 2.3 to 8.3), and the median progression-free survival was 5.6 months (95% CI, 4.1 to 8.3). In the combination-therapy group (28 evaluable patients), the response was 46% (95% CI, 28 to 66). The median response duration was 7.6 months (95% CI, 5.7 to not estimable), and the median progression-free survival was 6.9 months (95% CI, 5.4 to 8.1). The percentage of grade 3 or 4 treatment-related adverse events was 34% in the monotherapy group and 16% in the combination-therapy group. No grade 5 adverse events were observed.ConclusionsAdagrasib had antitumor activity in heavily pretreated patients with metastatic colorectal cancer with mutant KRAS G12C, both as oral monotherapy and in combination with cetuximab. The median response duration was more than 6 months in the combination-therapy group. Reversible adverse events were common in the two groups. (Funded by Mirati Therapeutics; KRYSTAL-1 ClinicalTrials.gov number, NCT03785249.)

High incidence and reversible bradycardia events following alectinib initiation.

With the widespread use of alectinib in patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), its cardiotoxicity has gradually emerged, including new-onset sinus bradycardia (SB). However, the incidence, timing, severity, and risk factors of alectinib-induced bradycardia remain unknown. From January 2020 to June 2022, 93 patients with ALK-positive NSCLC treated with alectinib were enrolled in this retrospective analysis. These patients had heart rate (HR) recorded before and after alectinib administration. By reviewing electronic medical records and follow-up, the HR changes of patients during medication were recorded. The potential risk factors associated with alectinib-induced SB were explored. According to an HR cut-off of 60 beats per minute (bpm), 47 patients (50.54%) experienced at least one recorded bradycardia. The mean HR of total participants before alectinib administration was 78.32 (standard deviation [SD], 9.48) and after was 64.88 (SD, 12.21). The median maximum change in HR (range) for all patients was 11 (-55, +4) bpm. For the bradycardia subgroup, the HR of most patients (76.60%) hovered around 50-60 bpm, and 61.70% of SB occurred within 3months after alectinib administration. Multivariate analysis indicated that baseline HR (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.79-0.93, p< 0.001) and history of hypertension (OR 13.71, 95% CI 2.49-76.38, p= 0.003) were independent risk factors for alectinib-related bradycardia. Alectinib-induced bradycardia had a high incidence, appeared relatively early, and was reversible by dose reduction or withdrawal.

Application of a Human Blood Brain Barrier Organ-on-a-Chip Model to Evaluate Small Molecule Effectiveness against Venezuelan Equine Encephalitis Virus.

The blood brain barrier (BBB) is a multicellular microenvironment that plays an important role in regulating bidirectional transport to and from the central nervous system (CNS). Infections by many acutely infectious viruses such as alphaviruses and flaviviruses are known to impact the integrity of the endothelial lining of the BBB. Infection by Venezuelan Equine Encephalitis Virus (VEEV) through the aerosol route causes significant damage to the integrity of the BBB, which contributes to long-term neurological sequelae. An effective therapeutic intervention strategy should ideally not only control viral load in the host, but also prevent and/or reverse deleterious events at the BBB. Two dimensional monocultures, including trans-well models that use endothelial cells, do not recapitulate the intricate multicellular environment of the BBB. Complex in vitro organ-on-a-chip models (OOC) provide a great opportunity to introduce human-like experimental models to understand the mechanistic underpinnings of the disease state and evaluate the effectiveness of therapeutic candidates in a highly relevant manner. Here we demonstrate the utility of a neurovascular unit (NVU) in analyzing the dynamics of infection and proinflammatory response following VEEV infection and therapeutic effectiveness of omaveloxolone to preserve BBB integrity and decrease viral and inflammatory load.

Tetra(peri-naphthylene)anthracene: A Near-IR Fluorophore with Four-Stage Amphoteric Redox Properties.

A novel, benign synthetic strategy towards soluble tetra(peri-naphthylene)anthracene (TPNA) decorated with triisopropylsilylethynyl substituents has been established. The compound is perfectly stable under ambient conditions in air and features intense and strongly bathochromically shifted UV/vis absorption and emission bands reaching to near-IR region beyond 900 nm. Cyclic voltammetry measurements revealed four facilitated reversible redox events comprising two oxidations and two reductions. These remarkable experimental findings were corroborated by theoretical studies to identify the TPNA platform a particularly useful candidate for the development of functional near-IR fluorophores upon appropriate functionalization.

Tromancenium complexes with steric and electronic modulation

A series of new heteroleptic cationic (η7-cycloheptatrienyl)(η5-cyclopentadienyl)manganese(I) (“tromancenium”) sandwich complexes containing the cycloheptatrienyl ligand and various sterically bulky cyclopentadienyl ligands was synthesized in a one-pot two-step procedure via their cymantrene precursors by high-power LED photochemistry followed by oxidation. In comparison to their less-substituted congeners which display only partially reversible redox events, these new air-stable tromancenium salts show reversible Mn(I)/Mn(II) and quasi-reversible Mn(I)/Mn(0) redox couples, as intended by the conceptual design of this work. Full spectroscopic and structural characterization of by 1H, 13C, 55Mn NMR, IR, UV–vis spectroscopy, high-resolution mass spectrometry and single crystal structure analysis is reported.

Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage

Direct oral anticoagulant (DOAC)-associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH are limited. To evaluate the safety and outcomes of DOAC reversal agents among patients with ICH. PubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022. The eligibility criteria were (1) adult patients (age ≥18 years) with ICH receiving treatment with a DOAC, (2) reversal of DOAC, and (3) reported safety and anticoagulation reversal outcomes. All nonhuman studies and case reports, studies evaluating patients with ischemic stroke requiring anticoagulation reversal or different dosing regimens of DOAC reversal agents, and mixed study groups with DOAC and warfarin were excluded. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for abstracting data and assessing data quality and validity. Two reviewers independently selected the studies and abstracted data. Data were pooled using the random-effects model. The primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent. A total of 36 studies met criteria for inclusion, with a total of 1832 patients (967 receiving 4-factor prothrombin complex concentrate [4F-PCC]; 525, andexanet alfa [AA]; 340, idarucizumab). The mean age was 76 (range, 68-83) years, and 57% were men. For 4F-PCC, anticoagulation reversal was 77% (95% CI, 72%-82%; I2 = 55%); all-cause mortality, 26% (95% CI, 20%-32%; I2 = 68%), and thromboembolic events, 8% (95% CI, 5%-12%; I2 = 41%). For AA, anticoagulation reversal was 75% (95% CI, 67%-81%; I2 = 48%); all-cause mortality, 24% (95% CI, 16%-34%; I2 = 73%), and thromboembolic events, 14% (95% CI, 10%-19%; I2 = 16%). Idarucizumab for reversal of dabigatran had an anticoagulation reversal rate of 82% (95% CI, 55%-95%; I2 = 41%), all-cause mortality, 11% (95% CI, 8%-15%, I2 = 0%), and thromboembolic events, 5% (95% CI, 3%-8%; I2 = 0%). A direct retrospective comparison of 4F-PCC and AA showed no differences in anticoagulation reversal, proportional mortality, or thromboembolic events. In the absence of randomized clinical comparison trials, the overall anticoagulation reversal, mortality, and thromboembolic event rates in this systematic review and meta-analysis appeared similar among available DOAC reversal agents for managing ICH. Cost, institutional formulary status, and availability may restrict reversal agent choice, particularly in small community hospitals.