Multi-cohort analysis of host immune response identifies conserved protective and detrimental modules associated with severity across viruses.

Viral infections induce a conserved host response distinct from bacterial infections. We hypothesized that the conserved response is associated with disease severity and is distinct between patients with different outcomes. To test this, we integrated 4,780 blood transcriptome profiles from patients aged 0 to 90 years infected with one of 16 viruses, including SARS-CoV-2, Ebola, chikungunya, and influenza, across 34 cohorts from 18 countries, and single-cell RNA sequencing profiles of 702,970 immune cells from 289 samples across three cohorts. Severe viral infection was associated with increased hematopoiesis, myelopoiesis, and myeloid-derived suppressor cells. We identified protective and detrimental gene modules that defined distinct trajectories associated with mild versus severe outcomes. The interferon response was decoupled from the protective host response in patients with severe outcomes. These findings were consistent, irrespective of age and virus, and provide insights to accelerate the development of diagnostics and host-directed therapies to improve global pandemic preparedness.

A platform for distributed production of synthetic nitrated proteins in live bacteria.

The incorporation of the nonstandard amino acid para-nitro-L-phenylalanine (pN-Phe) within proteins has been used for diverse applications, including the termination of immune self-tolerance. However, the requirement for the provision of chemically synthesized pN-Phe to cells limits the contexts where this technology can be harnessed. Here we report the construction of a live bacterial producer of synthetic nitrated proteins by coupling metabolic engineering and genetic code expansion. We achieved the biosynthesis of pN-Phe in Escherichia coli by creating a pathway that features a previously uncharacterized nonheme diiron N-monooxygenase, which resulted in pN-Phe titers of 820 ± 130 µM after optimization. After we identified an orthogonal translation system that exhibited selectivity toward pN-Phe rather than a precursor metabolite, we constructed a single strain that incorporated biosynthesized pN-Phe within a specific site of a reporter protein. Overall, our study has created a foundational technology platform for distributed and autonomous production of nitrated proteins.

MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters.

With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC. We simultaneously constructed an accompanying online database of BGCs, which has since been widely used by the community as a reference dataset for BGCs and was expanded to 2021 entries in 2019 (MIBiG 2.0). Here, we describe MIBiG 3.0, a database update comprising large-scale validation and re-annotation of existing entries and 661 new entries. Particular attention was paid to the annotation of compound structures and biological activities, as well as protein domain selectivities. Together, these new features keep the database up-to-date, and will provide new opportunities for the scientific community to use its freely available data, e.g. for the training of new machine learning models to predict sequence-structure-function relationships for diverse natural products. MIBiG 3.0 is accessible online at https://mibig.secondarymetabolites.org/.

Sample-Treatment with the Virucidal ß-Propiolactone Does Not Preclude Analysis by Large Panel Affinity Proteomics, Including the Discovery of Biomarker Candidates.

Virus inactivation is a prerequisite for safe handling of high-risk infectious samples. ß-Propiolactone (BPL) is an established reagent with proven virucidal efficacy. BPL primarily reacts with DNA, RNA, and amino acids. The latter may modify antigenic protein epitopes interfering with binding properties of affinity reagents such as antibodies and aptamers used in affinity proteomic screens. We investigated (i) the impact of BPL treatment on the analysis of protein levels in plasma samples using the aptamer-based affinity proteomic platform SomaScan and (ii) effects on protein detection in conditioned medium samples using the proximity extension assay-based Olink Target platform. In the former setup, BPL-treated and native plasma samples from patients with ovarian cancer (n = 12) and benign diseases (n = 12) were analyzed using the SomaScan platform. In the latter, conditioned media samples collected from cultured T cells with (n = 3) or without (n = 3) anti-CD3 antibody stimulation were analyzed using the Olink Target platform. BPL-related changes in protein detection were evaluated comparing native and BPL-treated states, simulating virus inactivation, and impact on measurable group differences was assessed. While approximately one-third of SomaScan measurements were significantly changed by the BPL treatment, a majority of antigen/aptamer interactions remained unaffected. Interaction effects of BPL treatment and disease state, potentially altering detectability of group differences, were observable for less than one percent of targets (0.6%). BPL effects on protein detection with Olink Target were also limited, affecting 3.6% of detected proteins with no observable interaction effects. Thus, effects of BPL treatment only moderately interfere with affinity proteomic detectability of differential protein expression between different experimental groups. Overall, the results prove high-throughput affinity proteomics well suited for the analysis of high-risk samples inactivated using BPL.

Reductive amination cascades in cell-free and resting whole cell formats for valorization of lignin deconstruction products.

The selective introduction of amine groups within deconstruction products of lignin could provide an avenue for valorizing waste biomass while achieving a green synthesis of industrially relevant building blocks from sustainable sources. Here, we built and characterized enzyme cascades that create aldehydes and subsequently primary amines from diverse lignin-derived carboxylic acids using a carboxylic acid reductase (CAR) and an ω-transaminase (TA). Unlike previous studies that have paired CAR and TA enzymes, here we examine multiple homologs of each of these enzymes and a broader set of candidate substrates. In addition, we compare the performance of these systems in cell-free and resting whole-cell biocatalysis formats using the conversion of vanillate to vanillyl amine as model chemistry. We also demonstrate that resting whole cells can be recycled for multiple batch reactions. We used the knowledge gained from this study to produce several amines from carboxylic acid precursors using one-pot biocatalytic reactions, several of which we report for the first time. These results expand our knowledge of these industrially relevant enzyme families to new substrates and contexts for environmentally friendly and potentially low-cost synthesis of diverse aryl aldehydes and amines.

Predictors of Emotional Prosody Identification by School-Age Children With Cochlear Implants and Their Peers With Normal Hearing.

OBJECTIVES: Children with cochlear implants (CIs) vary widely in their ability to identify emotions in speech. The causes of this variability are unknown, but this knowledge will be crucial if we are to design improvements in technological or rehabilitative interventions that are effective for individual patients. The objective of this study was to investigate how well factors such as age at implantation, duration of device experience (hearing age), nonverbal cognition, vocabulary, and socioeconomic status predict prosody-based emotion identification in children with CIs, and how the key predictors in this population compare to children with normal hearing who are listening to either normal emotional speech or to degraded speech. DESIGN: We measured vocal emotion identification in 47 school-age CI recipients aged 7 to 19 years in a single-interval, 5-alternative forced-choice task. None of the participants had usable residual hearing based on parent/caregiver report. Stimuli consisted of a set of semantically emotion-neutral sentences that were recorded by 4 talkers in child-directed and adult-directed prosody corresponding to five emotions: neutral, angry, happy, sad, and scared. Twenty-one children with normal hearing were also tested in the same tasks; they listened to both original speech and to versions that had been noise-vocoded to simulate CI information processing. RESULTS: Group comparison confirmed the expected deficit in CI participants' emotion identification relative to participants with normal hearing. Within the CI group, increasing hearing age (correlated with developmental age) and nonverbal cognition outcomes predicted emotion recognition scores. Stimulus-related factors such as talker and emotional category also influenced performance and were involved in interactions with hearing age and cognition. Age at implantation was not predictive of emotion identification. Unlike the CI participants, neither cognitive status nor vocabulary predicted outcomes in participants with normal hearing, whether listening to original speech or CI-simulated speech. Age-related improvements in outcomes were similar in the two groups. Participants with normal hearing listening to original speech showed the greatest differences in their scores for different talkers and emotions. Participants with normal hearing listening to CI-simulated speech showed significant deficits compared with their performance with original speech materials, and their scores also showed the least effect of talker- and emotion-based variability. CI participants showed more variation in their scores with different talkers and emotions than participants with normal hearing listening to CI-simulated speech, but less so than participants with normal hearing listening to original speech. CONCLUSIONS: Taken together, these results confirm previous findings that pediatric CI recipients have deficits in emotion identification based on prosodic cues, but they improve with age and experience at a rate that is similar to peers with normal hearing. Unlike participants with normal hearing, nonverbal cognition played a significant role in CI listeners' emotion identification. Specifically, nonverbal cognition predicted the extent to which individual CI users could benefit from some talkers being more expressive of emotions than others, and this effect was greater in CI users who had less experience with their device (or were younger) than CI users who had more experience with their device (or were older). Thus, in young prelingually deaf children with CIs performing an emotional prosody identification task, cognitive resources may be harnessed to a greater degree than in older prelingually deaf children with CIs or than children with normal hearing.

Combinatorial gene inactivation of aldehyde dehydrogenases mitigates aldehyde oxidation catalyzed by E. coli resting cells.

Aldehydes are attractive chemical targets both as end products in the flavors and fragrances industry and as synthetic intermediates due to their propensity for C-C bond formation. Here, we identify and address unexpected oxidation of a model collection of aromatic aldehydes, including many that originate from biomass degradation. When diverse aldehydes are supplemented to E. coli cells grown under aerobic conditions, as expected they are either reduced by the wild-type MG1655 strain or stabilized by a strain engineered for reduced aromatic aldehyde reduction (the E. coli RARE strain). Surprisingly, when these same aldehydes are supplemented to resting cell preparations of either E. coli strain, under many conditions we observe substantial oxidation. By performing combinatorial inactivation of six candidate aldehyde dehydrogenase genes in the E. coli genome using multiplexed automatable genome engineering (MAGE), we demonstrate that this oxidation can be substantially slowed, with greater than 50% retention of 6 out of 8 aldehydes when assayed 4 h after their addition. Given that our newly engineered strain exhibits reduced oxidation and reduction of aromatic aldehydes, we dubbed it the E. coli ROAR strain. We applied the new strain to resting cell biocatalysis for two kinds of reactions - the reduction of 2-furoic acid to furfural and the condensation of 3-hydroxybenzaldehyde and glycine to form a non-standard ß-hydroxy-α-amino acid. In each case, we observed substantial improvements in product titer 20 h after reaction initiation (9-fold and 10-fold, respectively). Moving forward, the use of this strain to generate resting cells should allow aldehyde product isolation, further enzymatic conversion, or chemical reactivity under cellular contexts that better accommodate aldehyde toxicity.

A Future Blood Test to Detect Cerebral Aneurysms.

Intracranial aneurysms are reported to affect 2-5% of the population. Despite advances in the surgical management of this disease, diagnostic technologies have marginally improved and still rely on expensive or invasive imaging procedures. Currently, there is no blood-based test to detect cerebral aneurysm formation or quantify the risk of rupture. The aim of this review is to summarize current literature on the mechanism of aneurysm formation, specifically studies relating to inflammation, and provide a rationale and commentary on a hypothetical future blood-based test. Efforts should be focused on clinical-translational approaches to create an assay to screen for cerebral aneurysm presence and risk-stratify patients to allow for superior treatment timing and management. Cerebral Aneurysm Blood Test Considerations: There are multiple caveats to development of a putative blood test to detect cerebral aneurysm presence.

The chemical inventory of the inner regions of planet-forming disks - the JWST/MINDS program.

The understanding of planet formation has changed recently, embracing the new idea of pebble accretion. This means that the influx of pebbles from the outer regions of planet-forming disks to their inner zones could determine the composition of planets and their atmospheres. The solid and molecular components delivered to the planet-forming region can be best characterized by mid-infrared spectroscopy. With Spitzer low-resolution (R = 100, 600) spectroscopy, this approach was limited to the detection of abundant molecules, such as H2O, C2H2, HCN and CO2. This contribution will present the first results of the MINDS (MIRI mid-INfrared Disk Survey, PI:Th Henning) project. Due do the sensitivity and spectral resolution provided by the James Webb Space Telescope (JWST), we now have a unique tool to obtain the full inventory of chemistry in the inner disks of solar-type stars and brown dwarfs, including also less-abundant hydrocarbons and isotopologues. The Integral Field Unit (IFU) capabilities will enable at the same time spatial studies of the continuum and line emission in extended sources such as debris disks, the flying saucer and also the search for mid-IR signatures of forming planets in systems such as PDS 70. These JWST observations are complementary to ALMA and NOEMA observations of outer-disk chemistry; together these datasets will provide an integral view of the processes occurring during the planet-formation phase.

Exome sequence analysis of rare frequency variants in Late-Onset Alzheimer Disease.

Alzheimer disease (AD) is a leading cause of dementia in elderly patients who continue to live between 3 and 11 years of diagnosis. A steep rise in AD incidents is observed in the elderly population in East-Asian countries. The disease progresses through several changes, including memory loss, behavioural issues, and cognitive impairment. The etiology of AD is hard to determine because of its complex nature. The whole exome sequences of late-onset AD (LOAD) patients of Korean origin are investigated to identify rare genetic variants that may influence the complex disorder. Computational annotation was performed to assess the function of candidate variants in LOAD. The in silico pathogenicity prediction tools such as SIFT, Polyphen-2, Mutation Taster, CADD, LRT, PROVEAN, DANN, VEST3, fathmm-MKL, GERP + + , SiPhy, phastCons, and phyloP identified around 17 genes harbouring deleterious variants. The variants in the ALDH3A2 and RAD54B genes were pathogenic, while in 15 other genes were predicted to be variants of unknown significance. These variants can be potential risk candidates contributing to AD. In silico computational techniques such as molecular docking, molecular dynamic simulation and steered molecular dynamics were carried out to understand the structural insights of RAD54B with ATP. The simulation of mutant (T459N) RAD54B with ATP revealed reduced binding strength of ATP at its binding site. In addition, lower binding free energy was observed when compared to the wild-type RAD54B. Our study shows that the identified uncommon variants are linked to AD and could be probable predisposing genetic factors of LOAD.

Interaction of admission platelet count with current medications and the risk for chronic subdural recurrence.

OBJECTIVE: Chronic subdural hematoma (cSDH) has a reported 10%-24% rate of recurrence after surgery, and prognostic models for recurrence have produced equivocal results. The objective of this study was to leverage a data mining algorithm, chi-square automatic interaction detection (CHAID), which can incorporate continuous, nominal, and binary data into a decision tree, to identify the most robust predictors of repeat surgery for cSDH patients. METHODS: This was a retrospective cohort study of all patients with SDH from two level 1 trauma centers at a single institution. All patients underwent cSDH evacuation performed by 15 neurosurgeons between 2011 and 2020. The primary outcome was the rate of repeat surgery for recurrent cSDH following the initial evacuation. The authors used CHAID to identify relevant predictors of repeat surgery, including age, sex, comorbidities, postsurgical complications, platelet count prior to the first procedure, midline shift prior to the first procedure, hematoma volume, and preoperative use of anticoagulants, antiplatelets, or statins. RESULTS: Sixty (13.8%) of 435 study-eligible patients (average age 74.0 years) had a cSDH recurrence. These patients had 2.0 times greater odds of having used anticoagulants. The final CHAID model had an overall accuracy of 87.4% and an area under the curve of 0.76. According to the model, the predictor with the strongest association with cSDH recurrence was admission platelet count. Approximately 26% of patients (n = 23/87) with an admission platelet count < 157 × 109/L had a cSDH recurrence, whereas none of the 44 patients with admission platelets > 313 × 109/L had a recurrence. Approximately 17% of patients in the 157-313 × 109/L platelet group who had used preoperative statins required a second procedure, which was associated with a 2.3 times increased risk for repeat surgery compared to those who had not used statins preoperatively. Among those who had not used preoperative statins, a platelet count ≤ 179 × 109/L on admission for the first procedure was the strongest differentiator for a second surgery (n = 5/22 [23%]), which increased the risk of recurrence by 4.5 times. Among the patients using preoperative statins, the use of anticoagulants was the strongest differentiator for requiring repeat surgery (n = 11/33 [33%]). CONCLUSIONS: The described model identified platelet count on admission as the most important predictor of repeat cSDH surgery, followed by preoperative statin use and anticoagulant use. Critical cutoffs for platelet count were identified, which future studies should evaluate to determine if they are modifiable or reflective of underlying disease states.

Arachnoid webs causing rostral syrinx due to ball-valve effect: an illustrative report of two cases.

An arachnoid web is a pathological formation of the arachnoid membrane. It is a rare phenomenon but is known to lead to syrinx formation in the spinal cord along with pain and neurological deficits. On imaging, the 'scalpel sign' is pathognomonic for an arachnoid web. The etiology of syrinx formation from an arachnoid web is currently unknown. This report documents the only two cases of arachnoid webs with an extensive syrinx in which a likely pathophysiologic mechanism is identified. Both cases presented with motor deficits. The patients had no history of trauma or infection. After extensive workup in both patients and observation of the scalpel sign an arachnoid web was suspected. In both cases, the patients were treated surgically after an arachnoid web was suspected. Intra-operative ultrasound visualized in both cases demonstrates a fenestration in the web that allowed passage of cerebrospinal fluid in a rostral-caudal direction due to a ball-valve effect.

Frozen Section Biopsy and Nephron-Sparing Surgery for a Multiloculated Cyst of the Kidney; Is this the Ideal Approach?

Multiloculated cystic renal masses are uncommon in the pediatric population. The presentation may be as an asymptomatic incidental finding on imaging, abdominal mass, abdominal pain, or urinary tract infection. The differentiation between benign and malignant causes of a cystic lesion by clinical and radiological examination is difficult. Tru-cut biopsy is not recommended due to fear of upgrading a malignant tumor. A definitive diagnosis is confirmed histopathologically only after surgery. Based on certain imaging characteristics, benign nature can be suspected and a conservative approach to surgery can be contemplated to save the kidney. Frozen section biopsy is useful in ruling out malignancy while doing nephron-sparing surgery (NSS) in these patients. NSS may be done by an open or minimally invasive approach. After histological confirmation of cystic nephroma, no other adjuvant treatment is necessary, but long-term surveillance is strongly recommended.

Bilateral Synchronous Robotic-Assisted Adrenalectomies in a Patient of Bilateral Pheochromocytoma and Von Hippel-Lindau Disease - A Rewarding Approach.

Hypertensive crisis is rare in children. Among the rarest causes leading to this acute crisis, is bilateral adrenal tumour as a part of a syndrome, Von Hippel Lindau syndrome. The treatment is based on the excision of the adrenal tumour followed by long term surviellence. The authors present a case where conventional imaging with ultrasound and contrast enhanced CT scan demonstrated a right side adrenal tumour with raised catecholamines. The small left side tumour got missed on conventional imaging and got picked up on DOTA scan. The persistence of hypertension in post operative period can be related to such hidden functioning tumours. In view of the size of tumour & raised dopamine associated with high incidence of malignancy, robotic surgery was used for bilateral adrenal tumour excision which confirmed the diagnosis of Pheochromocytoma (PCC).

Right Phrenic Nerve Palsy following Long-gap Esophageal Atresia and Tracheoesophageal Fistula Repair.

Esophageal atresia (EA) and tracheoesophageal fistula (TEF) are surgically correctable congenital anomalies with reported surgical common complications such as anastomotic leaks, recurrent TEF, and esophageal strictures; however, phrenic nerve injury (PNI) is a very rare but possible complication which we have highlighted in our case report. Here, we report a baby girl operated for long-gap EA and TEF having respiratory distress and failed attempts to wean off oxygen support. Serial chest X-rays showed elevated right hemidiaphragm, whereas ultrasound thorax confirmed our diagnosis of right PNI causing diaphragmatic palsy. Conservative management with the hope of spontaneous recovery failed, so diaphragmatic plication was done at 5 weeks from index surgery. Postplication, the baby was weaned off oxygen and pressure support the very 1st day and had improved respiratory physiology.

Loss of REST in breast cancer promotes tumor progression through estrogen sensitization, MMP24 and CEMIP overexpression.

BACKGROUND: Breast cancer is the most common malignancy in women, and is both pathologically and genetically heterogeneous, making early detection and treatment difficult. A subset of breast cancers express normal levels of REST (repressor element 1 silencing transcription factor) mRNA but lack functional REST protein. Loss of REST function is seen in ~ 20% of breast cancers and is associated with a more aggressive phenotype and poor prognosis. Despite the frequent loss of REST, little is known about the role of REST in the molecular pathogenesis of breast cancer. METHODS: TCGA data was analyzed for the expression of REST target genes in breast cancer patient samples. We then utilized gene knockdown in MCF-7 cells in the presence or absence of steroid hormones estrogen and/ progesterone followed by RNA sequencing, as well as chromatin immunoprecipitation and PCR in an attempt to understand the tumor suppressor role of REST in breast cancer. RESULTS: We show that REST directly regulates CEMIP (cell migration-inducing and hyaluronan-binding protein, KIAA1199) and MMP24 (matrix metallopeptidase 24), genes known to have roles in invasion and metastasis. REST knockdown in breast cancer cells leads to significant upregulation of CEMIP and MMP24. In addition, we found REST binds to RE-1 sites (repressor element-1) within the genes and influences their transcription. Furthermore, we found that the estrogen receptor (ESR1) signaling pathway is activated in the absence of REST, regardless of hormone treatment. CONCLUSIONS: We demonstrate a critical role for the loss of REST in aggressive breast cancer pathogenesis and provide evidence for REST as an important diagnostic marker for personalized treatment plans.

Evolthon: A community endeavor to evolve lab evolution.

In experimental evolution, scientists evolve organisms in the lab, typically by challenging them to new environmental conditions. How best to evolve a desired trait? Should the challenge be applied abruptly, gradually, periodically, sporadically? Should one apply chemical mutagenesis, and do strains with high innate mutation rate evolve faster? What are ideal population sizes of evolving populations? There are endless strategies, beyond those that can be exposed by individual labs. We therefore arranged a community challenge, Evolthon, in which students and scientists from different labs were asked to evolve Escherichia coli or Saccharomyces cerevisiae for an abiotic stress-low temperature. About 30 participants from around the world explored diverse environmental and genetic regimes of evolution. After a period of evolution in each lab, all strains of each species were competed with one another. In yeast, the most successful strategies were those that used mating, underscoring the importance of sex in evolution. In bacteria, the fittest strain used a strategy based on exploration of different mutation rates. Different strategies displayed variable levels of performance and stability across additional challenges and conditions. This study therefore uncovers principles of effective experimental evolutionary regimens and might prove useful also for biotechnological developments of new strains and for understanding natural strategies in evolutionary arms races between species. Evolthon constitutes a model for community-based scientific exploration that encourages creativity and cooperation.

Stimulation of glycolysis promotes cardiomyocyte proliferation after injury in adult zebrafish.

Cardiac metabolism plays a crucial role in producing sufficient energy to sustain cardiac function. However, the role of metabolism in different aspects of cardiomyocyte regeneration remains unclear. Working with the adult zebrafish heart regeneration model, we first find an increase in the levels of mRNAs encoding enzymes regulating glucose and pyruvate metabolism, including pyruvate kinase M1/2 (Pkm) and pyruvate dehydrogenase kinases (Pdks), especially in tissues bordering the damaged area. We further find that impaired glycolysis decreases the number of proliferating cardiomyocytes following injury. These observations are supported by analyses using loss-of-function models for the metabolic regulators Pkma2 and peroxisome proliferator-activated receptor gamma coactivator 1 alpha. Cardiomyocyte-specific loss- and gain-of-function manipulations of pyruvate metabolism using Pdk3 as well as a catalytic subunit of the pyruvate dehydrogenase complex (PDC) reveal its importance in cardiomyocyte dedifferentiation and proliferation after injury. Furthermore, we find that PDK activity can modulate cell cycle progression and protrusive activity in mammalian cardiomyocytes in culture. Our findings reveal new roles for cardiac metabolism and the PDK-PDC axis in cardiomyocyte behavior following cardiac injury.

Optimal Medical Therapy Following Deep Venous Interventions: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel.

The optimal medical management of patients following endovascular deep venous interventions remains ill-defined. As such, the Society of Interventional Radiology Foundation (SIRF) convened a multidisciplinary group of experts in a virtual Research Consensus Panel (RCP) to develop a prioritized research agenda regarding antithrombotic therapy following deep venous interventions. The panelists presented the gaps in knowledge followed by discussion and ranking of research priorities based on clinical relevance, overall impact, and technical feasibility. The following research topics were identified as high priority: 1) characterization of biological processes leading to in-stent stenosis/rethrombosis; 2) identification and validation of methods to assess venous flow dynamics and their effect on stent failure; 3) elucidation of the role of inflammation and anti-inflammatory therapies; and 4) clinical studies to compare antithrombotic strategies and improve venous outcome assessment. Collaborative, multicenter research is necessary to answer these questions and thereby enhance the care of patients with venous disease.

Antithrombotic Therapy After Venous Interventions: AJR Expert Panel Narrative Review.

Interventions for thrombotic and nonthrombotic venous disorders have increased with technical advances and more trained venous specialists. Antithrombotic therapy is essential to clinical and procedural success; however, postprocedural therapeutic regimens exhibit significant heterogeneity due to limited prospective randomized data and incomplete mechanistic understanding of the critical factors driving long-term patency. Postinterventional antithrombotic therapy for thrombotic venous disorders should adhere to existing venous thromboembolism management guidelines, which include 3-6 months of therapeutic anticoagulation at minimum and consideration of extended therapy in patients with higher risk of thrombosis because of procedural or patient factors. The added benefit of antiplatelet agents in the acute and intermediate period is unknown, having shown improved long-term stent patency in some retrospective studies. Dual- and/or triple-agent therapy should be limited based on individual risks of thrombosis and bleeding. The treatment of nonthrombotic disorders is more heterogeneous, though patients with limited flow, extensive stent material, or underlying prothrombotic states such as malignancy or chronic inflammation may benefit from single-agent or multiagent antithrombotic therapy. However, the agent, dose, and duration of therapy remain indeterminate. Future prospective studies are warranted to improve patient risk stratification and standardize postprocedural anti-thrombotic therapy in patients receiving venous interventions.