Analysis of 3D pathology samples using weakly supervised AI.

Human tissue, which is inherently three-dimensional (3D), is traditionally examined through standard-of-care histopathology as limited two-dimensional (2D) cross-sections that can insufficiently represent the tissue due to sampling bias. To holistically characterize histomorphology, 3D imaging modalities have been developed, but clinical translation is hampered by complex manual evaluation and lack of computational platforms to distill clinical insights from large, high-resolution datasets. We present TriPath, a deep-learning platform for processing tissue volumes and efficiently predicting clinical outcomes based on 3D morphological features. Recurrence risk-stratification models were trained on prostate cancer specimens imaged with open-top light-sheet microscopy or microcomputed tomography. By comprehensively capturing 3D morphologies, 3D volume-based prognostication achieves superior performance to traditional 2D slice-based approaches, including clinical/histopathological baselines from six certified genitourinary pathologists. Incorporating greater tissue volume improves prognostic performance and mitigates risk prediction variability from sampling bias, further emphasizing the value of capturing larger extents of heterogeneous morphology.

The MT1 receptor as the target of ramelteon neuroprotection in ischemic stroke.

Stroke is the leading cause of death and disability worldwide. Novel and effective therapies for ischemic stroke are urgently needed. Here, we report that melatonin receptor 1A (MT1) agonist ramelteon is a neuroprotective drug candidate as demonstrated by comprehensive experimental models of ischemic stroke, including a middle cerebral artery occlusion (MCAO) mouse model of cerebral ischemia in vivo, organotypic hippocampal slice cultures ex vivo, and cultured neurons in vitro; the neuroprotective effects of ramelteon are diminished in MT1-knockout (KO) mice and MT1-KO cultured neurons. For the first time, we report that the MT1 receptor is significantly depleted in the brain of MCAO mice, and ramelteon treatment significantly recovers the brain MT1 losses in MCAO mice, which is further explained by the Connectivity Map L1000 bioinformatic analysis that shows gene-expression signatures of MCAO mice are negatively connected to melatonin receptor agonist like Ramelteon. We demonstrate that ramelteon improves the cerebral blood flow signals in ischemic stroke that is potentially mediated, at least, partly by mechanisms of activating endothelial nitric oxide synthase. Our results also show that the neuroprotection of ramelteon counteracts reactive oxygen species-induced oxidative stress and activates the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway. Ramelteon inhibits the mitochondrial and autophagic death pathways in MCAO mice and cultured neurons, consistent with gene set enrichment analysis from a bioinformatics perspective angle. Our data suggest that Ramelteon is a potential neuroprotective drug candidate, and MT1 is the neuroprotective target for ischemic stroke, which provides new insights into stroke therapy. MT1-KO mice and cultured neurons may provide animal and cellular models of accelerated ischemic damage and neuronal cell death.

EFMC: Trends in Medicinal Chemistry and Chemical Biology.

Ground-breaking research in disease biology and continuous efforts in method development have uncovered a range of potential new drug targets. Increasingly, the drug discovery process is informed by technologies involving chemical probes as tools. Applications for chemical probes comprise target identification and assessment, as well as the qualification of small molecules as chemical starting points and drug candidates. Progress in probe chemistry has opened the way to novel assay formats and pharmaceutical compound classes. The European Federation of Medicinal Chemistry and Chemical Biology (EFMC) has launched the Chemical Biology Initiative to advance science in the field of medicinal chemistry and chemical biology, while representing all members of this extended scientific community. This review provides an overview of the many important developments in the field of chemical biology that have happened at the lively interface of academic and industrial research.

The Role of Reconstruction on Desmoid Tumor Recurrence: A Systematic Review and Technical Considerations.

BACKGROUND: Desmoid tumors occur throughout the body, presenting as aggressive, locally invasive lesions that can impede quality of life. Many controversies remain regarding the optimal surgical treatment of desmoid. This article presents a systematic review and meta-analysis on surgical management, focusing on risk of recurrence and the utility of reconstruction within this unique patient population. METHODS: A systematic review was conducted to search for articles. The clinical course of patients diagnosed with desmoid tumors and treated by our institution's multidisciplinary team was retrospectively reviewed over a 13-year period. Meta-analysis study findings were compared with our cohort. RESULTS: From the systematic review, 10 studies with level of evidence III were found, which resulted in 981 patients. Twenty patients from our institution met the inclusion criteria for our study. In both our study cohort and the pooled results, recurrence was significantly higher in patients with positive microscopic margin after resection. In our study cohort, patients with recurrence had higher rates of positive margins compared with those without recurrence (83.3% vs 7.1%, P = 0.004), whereas the pooled study showed a difference of margin positivity of 50% vs 40% ( P = 0.01). No patients who underwent reconstruction in our study cohort had a recurrence during the study period. CONCLUSION: In both our cohort and pooled results, recurrence was significantly higher in patients with positive margins after initial resection. Reconstruction was not found to be a risk factor for recurrence. Reconstruction following desmoid tumor resection should be considered a viable option if a large and aggressive resection is required to obtain negative margins.

Static and Dynamic Stabilization of the Shoulder After Total Scapulectomy in an Electric Burn Patient.

ABSTRACT: An otherwise healthy 49-year-old man experienced a high-voltage electrical injury to the left shoulder resulting in total scapulectomy, partial calviculectomy, and a substantial soft tissue defect. The majority of the muscles around his shoulder were debrided because of necrosis, with only the pectoralis and latissimus dorsi muscles remaining attached to the humerus. Surprisingly, the patient's brachial plexus remained intact, and his left elbow, wrist, and hand function were preserved. A novel combination of 3 static and dynamic suspension techniques were used to stabilize his shoulder and prevent traction injury to the brachial plexus. Postoperative follow-up at 1 year demonstrated excellent stability of his reconstructed shoulder, which allowed him to ambulate independently and return to employment.

Doubly Constrained Waveform Optimization for Integrated Sensing and Communications.

This paper investigates threshold-constrained joint waveform optimization for an integrated sensing and communication (ISAC) system. Unlike existing studies, we employ mutual information (MI) and sum rate (SR) as sensing and communication metrics, respectively, and optimize the waveform under constraints to both metrics simultaneously. This provides significant flexibility in meeting system performance. We formulate three different optimization problems that constrain the radar performance only, the communication performance only, and the ISAC performance, respectively. New techniques are developed to solve the original problems, which are NP-hard and cannot be directly solved by conventional semi-definite programming (SDP) techniques. Novel gradient descent methods are developed to solve the first two problems. For the third non-convex optimization problem, we transform it into a convex problem and solve it via convex toolboxes. We also disclose the connections between three optimizations using numerical results. Finally, simulation results are provided and validate the proposed optimization solutions.

Affi-BAMS™: A Robust Targeted Proteomics Microarray Platform to Measure Histone Post-Translational Modifications.

For targeted protein panels, the ability to specifically assay post-translational modifications (PTMs) in a quantitative, sensitive, and straightforward manner would substantially advance biological and pharmacological studies. The present study highlights the effectiveness of the Affi-BAMS™ epitope-directed affinity bead capture/MALDI MS platform for quantitatively defining complex PTM marks of H3 and H4 histones. Using H3 and H4 histone peptides and isotopically labelled derivatives, this affinity bead and MALDI MS platform achieves a range of >3 orders of magnitude with a technical precision CV of <5%. Using nuclear cellular lysates, Affi-BAMS PTM-peptide capture resolves heterogeneous histone N-terminal PTMs with as little as 100 µg of starting material. In an HDAC inhibitor and MCF7 cell line model, the ability to monitor dynamic histone H3 acetylation and methylation events is further demonstrated (including SILAC quantification). Affi-BAMS (and its capacity for the multiplexing of samples and target PTM-proteins) thus provides a uniquely efficient and effective approach for analyzing dynamic epigenetic histone marks, which is critical for the regulation of chromatin structure and gene expression.

Bayesian structural time series for biomedical sensor data: A flexible modeling framework for evaluating interventions.

The development of mobile-health technology has the potential to revolutionize personalized medicine. Biomedical sensors (e.g., wearables) can assist with determining treatment plans for individuals, provide quantitative information to healthcare providers, and give objective measurements of health, leading to the goal of precise phenotypic correlates for genotypes. Even though treatments and interventions are becoming more specific and datasets more abundant, measuring the causal impact of health interventions requires careful considerations of complex covariate structures, as well as knowledge of the temporal and spatial properties of the data. Thus, interpreting biomedical sensor data needs to make use of specialized statistical models. Here, we show how the Bayesian structural time series framework, widely used in economics, can be applied to these data. This framework corrects for covariates to provide accurate assessments of the significance of interventions. Furthermore, it allows for a time-dependent confidence interval of impact, which is useful for considering individualized assessments of intervention efficacy. We provide a customized biomedical adaptor tool, MhealthCI, around a specific implementation of the Bayesian structural time series framework that uniformly processes, prepares, and registers diverse biomedical data. We apply the software implementation of MhealthCI to a structured set of examples in biomedicine to showcase the ability of the framework to evaluate interventions with varying levels of data richness and covariate complexity and also compare the performance to other models. Specifically, we show how the framework is able to evaluate an exercise intervention's effect on stabilizing blood glucose in a diabetes dataset. We also provide a future-anticipating illustration from a behavioral dataset showcasing how the framework integrates complex spatial covariates. Overall, we show the robustness of the Bayesian structural time series framework when applied to biomedical sensor data, highlighting its increasing value for current and future datasets.

Characterizing Thrombotic Complication Risk Factors Associated With COVID-19 via Heterogeneous Patient Data: Retrospective Observational Study.

BACKGROUND: COVID-19 has been observed to be associated with venous and arterial thrombosis. The inflammatory disease prolongs hospitalization, and preexisting comorbidities can intensity the thrombotic burden in patients with COVID-19. However, venous thromboembolism, arterial thrombosis, and other vascular complications may go unnoticed in critical care settings. Early risk stratification is paramount in the COVID-19 patient population for proactive monitoring of thrombotic complications. OBJECTIVE: The aim of this exploratory research was to characterize thrombotic complication risk factors associated with COVID-19 using information from electronic health record (EHR) and insurance claims databases. The goal is to develop an approach for analysis using real-world data evidence that can be generalized to characterize thrombotic complications and additional conditions in other clinical settings as well, such as pneumonia or acute respiratory distress syndrome in COVID-19 patients or in the intensive care unit. METHODS: We extracted deidentified patient data from the insurance claims database IBM MarketScan, and formulated hypotheses on thrombotic complications in patients with COVID-19 with respect to patient demographic and clinical factors using logistic regression. The hypotheses were then verified with analysis of deidentified patient data from the Research Patient Data Registry (RPDR) Mass General Brigham (MGB) patient EHR database. Data were analyzed according to odds ratios, 95% CIs, and P values. RESULTS: The analysis identified significant predictors (P<.001) for thrombotic complications in 184,831 COVID-19 patients out of the millions of records from IBM MarketScan and the MGB RPDR. With respect to age groups, patients 60 years and older had higher odds (4.866 in MarketScan and 6.357 in RPDR) to have thrombotic complications than those under 60 years old. In terms of gender, men were more likely (odds ratio of 1.245 in MarketScan and 1.693 in RPDR) to have thrombotic complications than women. Among the preexisting comorbidities, patients with heart disease, cerebrovascular diseases, hypertension, and personal history of thrombosis all had significantly higher odds of developing a thrombotic complication. Cancer and obesity were also associated with odds>1. The results from RPDR validated the IBM MarketScan findings, as they were largely consistent and afford mutual enrichment. CONCLUSIONS: The analysis approach adopted in this study can work across heterogeneous databases from diverse organizations and thus facilitates collaboration. Searching through millions of patient records, the analysis helped to identify factors influencing a phenotype. Use of thrombotic complications in COVID-19 patients represents only a case study; however, the same design can be used across other disease areas by extracting corresponding disease-specific patient data from available databases.

Patterns and Predictors of Extra-Corporeal Membrane Oxygenation Related Cerebral Microbleeds.

OBJECTIVES: Recent case-reports have described an atypical cerebral microbleed (CMB) topography after extracorporeal membrane oxygenation (ECMO). The objective of this study was to examine the prevalence, radiographic patterns, and clinical correlates of possibly-ECMO-related (PER) CMB. MATERIALS AND METHODS: We performed a retrospective study of 307 consecutive patients receiving ECMO support at our tertiary-care University Hospital (2013-2018). PER CMB were defined as CMB present in corpus-callosum and/or middle cerebellar peduncle with/without involvement of other lobar/deep structures. Leukoaraiosis was quantified using the Wahlund age-related white matter changes scale. Patient characteristics were compared between cohorts with and without PER CMB. RESULTS: Forty patients (median age 60 years; 33% vv-ECMO and 67% va-ECMO) received at-least one MRI-brain within 3 months of ECMO support. CMB were present in 77.5% (n = 31) patients with 39% (n = 12), 17% (n = 5), and 44% (n = 14) having low (< 10 CMB), moderate (10-30 CMB), and high (> 30 CMB) burden respectively. Among CMB-positive patients, 71% (n = 22) had PER CMB, with 91% of such cases demonstrating involvement of splenium. Leukoaraiosis did not corelate to PER CMB presence (p = 0.267) or burden (ρ = 0.09). Patients with PER CMB had higher rates of ischemic stroke (50 vs. 33%), intracranial hemorrhage (41 vs. 17%), and all-cause mortality (27 vs. 17%); with survivors demonstrating no differences in their discharge disposition or modified Rankin Score. CONCLUSIONS: Post-ECMO cerebral microbleeds have a distinct distribution pattern that commonly involves the splenium of corpus-callosum. Their etiopathogenesis may be independent of microvascular lipohyalinosis. This requires further study in a larger sample-size.

Chemical biology approaches to study histone interactors.

Protein-protein interactions (PPIs) in the nucleus play key roles in transcriptional regulation and ensure genomic stability. Critical to this are histone-mediated PPI networks, which are further fine-tuned through dynamic post-translational modification. Perturbation to these networks leads to genomic instability and disease, presenting epigenetic proteins as key therapeutic targets. This mini-review will describe progress in mapping the combinatorial histone PTM landscape, and recent chemical biology approaches to map histone interactors. Recent advances in mapping direct interactors of histone PTMs as well as local chromatin interactomes will be highlighted, with a focus on mass-spectrometry based workflows that continue to illuminate histone-mediated PPIs in unprecedented detail.

The value of federated learning during and post-COVID-19.

Federated learning (FL) as a distributed machine learning (ML) technique has lately attracted increasing attention of healthcare stakeholders as FL is perceived as a promising decentralized approach to address data privacy and security concerns. The FL approach stores and maintains the privacy-sensitive data locally while allows multiple sites to train ML models collaboratively. We aim to describe the most recent real-world cases using the FL in both COVID-19 and non-COVID-19 scenarios and also highlight current limitations and practical challenges of FL.

Risk of Pneumothorax With Internal Mammary Vessel Utilization in Autologous Breast Reconstruction.

BACKGROUND: Complications associated with autologous breast reconstruction are well reported in the literature. Regardless of the type of free flap harvested, the anastomosis is most commonly performed to the recipient internal mammary vessels. Although pneumothorax is a known possible complication of breast surgery, incidence of pneumothorax in breast reconstruction involving the use of the internal mammary vessels is rarely discussed. The aim of our study was to determine the incidence of pneumothorax in deep inferior epigastric perforator (DIEP) flap breast reconstruction. METHODS: A single-institution review was performed examining the incidence of pneumothorax in cases of DIEP flap breast reconstruction with anastomosis to the internal mammary vessels over a 4-year period. Intraoperative irrigation was used to visually assess for evidence of pneumothorax during recipient vessel dissection and anastomosis. Anteroposterior chest radiographs were obtained on the first postoperative day to assess for pneumothorax. Additional variables analyzed included type of retractor used during recipient vessel dissection and history of radiation. RESULTS: A total of 180 patients underwent autologous DIEP breast reconstruction at our institution. The overall incidence of pneumothorax was 1.4 per 100 recipient vessel dissections and 2.2 per 100 patients undergoing breast reconstruction. There was a total of 4 cases of pneumothorax. Three were attributed to unknown causes, and 1 was due to direct injury to the parietal pleura via electrocautery. CONCLUSION: The use of the internal mammary artery and vein as recipient vessels continues to be the most common and reliable recipient for autologous breast reconstruction. Based on our data, pneumothorax does not seem to be a common complication of this procedure. If concern for iatrogenic injury to the pleura arises intraoperatively, we suggest the use of a saline bubble test to investigate the possible injury. Routine postoperative radiographs are not indicated unless the patient develops symptoms suggestive of pneumothorax.

Surgical Treatment of Upper Extremity Gunshot Injures: An Updated Review.

INTRODUCTION: Firearm morbidity and mortality have been increasing in recent years, and with this, the demand for medical personnel firearm injury treatment knowledge. Extremities contribute to a majority of firearm injuries, with these injuries being particularly complex because of neurovascular proximity within a confined space. Knowledge of firearm mechanism of injury and treatment management options is important for any trauma hand surgeon. Many factors play vital roles in the treatment of complex upper extremity (UE) gunshot wounds (GSWs). The aim of our review and case illustrations is to provide hand surgeons with an up-to-date guide for initial emergent management, soft tissue, bony, and nerve repair and reconstruction. PATIENT AND METHODS: A literature review was conducted in the current management of UE GSW injuries, and 2 specific patient case examples were included. High-energy versus low-energy GSWs were documented and compared, as well as containment injures. Management including soft tissue, bony, and nerve injuries was explored along with patient outcome. Based on these findings, guidelines for GSW management were purposed. CONCLUSION: Gunshot wounds of the UE encompass a group of highly heterogeneous injuries. High-energy wounds are more extensive, and concomitant injuries to bone, vessel, nerve, muscle, and soft tissue are common. Early treatment with adequate debridement, skeletal fixation, and soft tissue coverage is indicated for complex injuries, and antibiotic treatment in the pre-, peri-, and postoperative period is indicated for operative injuries. Soft tissue coverage options include the entire reconstructive ladder, with pattern of injury and considerations of wound characteristics dictating reconstructive choice. There are arguments to using either external or internal bony fixation techniques for bone fracture management, with choice tailored to the patient. For management of nerve injuries, we advocate earlier nerve repair and a shorter duration of observation before secondary reconstruction in selective cases. If transected nerve endings cannot be brought together, nerve autografts of shorter length are recommended to bridge nerve ending gaps. A significant number of patients with GSW fail to make necessary follow-up appointments, which adds to challenges in treatment.

Global Pandemic and Plastic Surgery Residency Match: Can Social Media Fill the Void?

BACKGROUND: The type of content that influences plastic and reconstructive surgery (PRS) residency program selection and attracts applicants is continually changing and not clearly understood. Further, the COVID-19 pandemic has had a major yet undetermined impact on residency selection. OBJECTIVES: The purpose of this study was to determine the type of PRS social media (SM) content that drives prospective applicants' interest in a residency program, and the degree of SM influence on applicants, especially in the context of COVID-19. METHODS: Prospective PRS residency applicants were surveyed anonymously. RESULTS: An average of 60% of respondents reported that PRS SM content influenced their perception of a program. Fifty-eight percent reported that resident lifestyle content made them more interested in a program. Separately, 32% reported that resident lifestyle content influenced them to rank a program higher. Seventy-two percent of respondents claimed SM content did not make them lose interest in a program. Rarely posting, outdated content, and lack of engagement were cited as factors for loss of interest in a program. A majority of respondents (53%) reported wanting to see more resident life and culture content on SM. Of the existing PRS SM content, respondents were most interested in resident lifestyle, followed by clinical and program-specific content. CONCLUSIONS: The COVID-19 pandemic amplified the importance of SM PRS residency selection. Resident lifestyle content was consistently indicated as more likely to make respondents gain interest in a program, rank a program higher, and as the most desired content. PRS programs will benefit from highlighting resident camaraderie, quality of life, hobbies, and lifestyle to attract applicants.

Old age and other factors associated with salivary microbiome variation.

BACKGROUND: Many factors can contribute to the exact makeup of the salivary microbiome. Differences in the oral microbiome occur with old age, which may be due to oral conditions and diseases associated with old age, such as edentulism, as well as other unknown causes. METHODS: The salivary microbiome was sampled in patients from a large urban clinic. For all subjects age, gender, periodontal status, caries status, presence of edentulism, medications, and tobacco usage were recorded. Multifactor analysis was used to study variation in salivary microbiome profiles linked to these factors. RESULTS: In the population sampled, there were significantly higher numbers of edentulous subjects, and increased levels of polypharmacy found with aging. Large differences in alpha diversity and beta diversity of the salivary microbiome in the old age group were largely linked to edentulism. However, multivariable analysis revealed, even after adjusting for differences in edentulism, polypharmacy, tobacco usage, periodontal disease, caries level, and gender, that old age itself was associated with lower levels of taxa Porphyromonas endodontalis, Alloprevotella tannerae, Filifactor alocis, Treponema, Lautropia Mirabilis and Pseudopropionibacterium sp._HMT_194. Surprisingly, of these taxa, most were ones known to reside on or near tooth surfaces. CONCLUSIONS: Another factor or factors beyond edentulism, polypharmacy and periodontal disease play a role in the differences seen in oral microbiome with old age. The nature of this factor(s) is not known.

Advanced Quality Training in Radiology: Inaugural Report of a 2-Year Program.

OBJECTIVE. The purpose of this study is to describe and analyze the outcomes of a 2-year advanced quality training program for radiology residents. MATERIALS AND METHODS. In 2016, the radiology quality committee of a quaternary health system created a hands-on 2-year advanced quality training curriculum for diagnostic and interventional radiology residents. Internal candidates with the following prerequisites submitted competitive applications: registration for a 2-day lean health care management course, completion of four or more Radiological Society of North America (RSNA) quality essentials certificates, identification of faculty mentor(s), selection of one quality improvement project to champion, and completion of a two-page essay summarizing interest in quality improvement, the proposed project, and its potential impact. Residents were required to attend monthly quality meetings, pursue their project and its derivatives, submit completed work for consideration to a national meeting and for publication, and present at departmental grand rounds. Outcomes were summarized using descriptive statistics. RESULTS. Five residents submitted four projects for consideration, and all five were selected. In addition to the four submitted projects, seven additional projects were pursued. Participants worked on nine local and three multicenter process improvements, gave one to two grand rounds each, presented three oral and five poster presentations, generated eight publications, received three awards, formed 14 mentor-mentee relationships, and influenced local and multisite practice patterns. Participants reported gaining firsthand experience in quality improvement principles and developing real-world leadership skills. CONCLUSION. A targeted 2-year curriculum emphasizing hands-on quality improvement experience with rich mentor-mentee relationships can produce meaningful results.

Characteristic Cerebrovascular Findings Associated with ACTA2 Gene Mutations.

A specific mutation (Arg179) of the ACTA2 gene has previously been described to cause a syndrome of multisystemic smooth muscle dysfunction with an extremely characteristic cerebrovascular appearance.1 Accurate neuroimaging diagnosis of this entity is important as this syndrome predisposes to complications such as early-onset ischemic stroke and ascending thoracic aortic aneurysm.2,3 The following case demonstrates a previously undescribed ACTA2 mutation (Met46) with an identical cerebrovascular imaging appearance to that of Arg179 mutations, but a less severe overall phenotype.

Sonography of Wrist Ganglion Cysts: Which Location Is Most Common?

OBJECTIVES: The literature states that wrist ganglion cysts are most commonly dorsal; however, our experience suggests a volar location is more common. The purpose of this study was to identify the locations of ganglion cysts of the wrist as imaged with sonography. METHODS: After Institutional Review Board approval with informed consent waived, retrospective review of wrist sonography reports from January to April 2016 was completed. Only patients who had a comprehensive evaluation that included the dorsal and volar wrist were included. Ultrasound images were reviewed to characterize wrist ganglion cysts. RESULTS: The study group consisted of 98 subjects (78% female, 22% male) (median age, 51 years; range 13-79) with 124 wrist ganglion cysts, where 69% (86 of 124) were volar and 31% (38 of 124) were dorsal. Ganglion cysts were located between the radial artery and flexor carpi radialis in 63% (78 of 124), followed by a dorsal location superficial to the scapholunate ligament in 20% (25 of 124), other dorsal locations in 11% (13 of 124), and other volar locations in 6% (8 of 124). With dorsal ganglion cysts, the scapholunate ligament when imaged appeared normal in 91% (20 of 22). Ganglion cysts were multilocular/multilobular in all subjects. CONCLUSIONS: The most common location for wrist ganglion cysts is in the volar wrist, particularly between the radial artery and flexor carpi radialis tendon, appearing multilocular or multilobular with a mean largest dimension of 1.0 cm. Given the propensity of ganglion cysts to occur at this site, attention to this area when imaging the wrist with sonography or magnetic resonance imaging should be considered.

A Systematic Literature Review of Patients With Carotid Web and Acute Ischemic Stroke.

Background and Purpose- Carotid web (CW) is a rare form of focal fibromuscular dysplasia defined as an abnormal shelf-like projection of intimal fibrous tissue into the carotid bulb. It is theorized that CW leads to ischemic stroke secondary to blood flow stasis and subsequent embolization. The natural history and optimal management of CW are unclear. To address this knowledge gap, we performed a systematic literature review (SLR) of CW. Methods- Our librarians performed a SLR for CW and related terminology. Patient-level demographics, stroke risk factors, neuroimaging findings, stroke recurrence or stroke free-duration, and treatment modality were extracted. We used descriptive statistics to characterize our results. When specific patient-level metrics were not reported, the denominators for reporting percentage calculations were adjusted accordingly. Results- Our literature search produced 1150 articles. Thirty-seven articles including 158 patients (median age 46 years [range 16-85], 68% women, 76% symptomatic) met entry criteria and were included in our SLR. Of the symptomatic CW patients: 57% did not have stroke risk factors, 56% who received medical therapy had recurrent stroke (median 12 months, range 0-97), and 72% were ultimately treated with carotid revascularization (50% carotid stenting, 50% carotid endarterectomy). There were no periprocedural complications or recurrent strokes in carotid revascularization patients. Conclusions- CW leads to ischemic stroke in younger patients without conventional stroke risk factors. We found a high stroke recurrence rate in medically managed symptomatic CW patients, whereas carotid revascularization effectively prevented recurrent stroke. Our findings should be interpreted with caution because of risk of publication and reporting bias.