Fibrin-targeting immunotherapy protects against neuroinflammation and neurodegeneration.

Activation of innate immunity and deposition of blood-derived fibrin in the central nervous system (CNS) occur in autoimmune and neurodegenerative diseases, including multiple sclerosis (MS) and Alzheimer's disease (AD). However, the mechanisms that link disruption of the blood-brain barrier (BBB) to neurodegeneration are poorly understood, and exploration of fibrin as a therapeutic target has been limited by its beneficial clotting functions. Here we report the generation of monoclonal antibody 5B8, targeted against the cryptic fibrin epitope γ377-395, to selectively inhibit fibrin-induced inflammation and oxidative stress without interfering with clotting. 5B8 suppressed fibrin-induced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and the expression of proinflammatory genes. In animal models of MS and AD, 5B8 entered the CNS and bound to parenchymal fibrin, and its therapeutic administration reduced the activation of innate immunity and neurodegeneration. Thus, fibrin-targeting immunotherapy inhibited autoimmunity- and amyloid-driven neurotoxicity and might have clinical benefit without globally suppressing innate immunity or interfering with coagulation in diverse neurological diseases.

RNAPII driven post-translational modifications of nucleosomal histones.

The current understanding of how specific distributions of histone post-translational modifications (PTMs) are achieved throughout the chromatin remains incomplete. This review focuses on the role of RNA polymerase II (RNAPII) in establishing H2BK120/K123 ubiquitination and H3K4/K36 methylation distribution. The rate of RNAPII transcription is mainly a function of the RNAPII elongation and recruitment rates. Two major mechanisms link RNAPII's transcription rate to the distribution of PTMs. First, the phosphorylation patterns of Ser2P/Ser5P in the C-terminal domain of RNAPII change as a function of time, since the start of elongation, linking them to the elongation rate. Ser2P/Ser5P recruits specific histone PTM enzymes/activators to the nucleosome. Second, multiple rounds of binding and catalysis by the enzymes are required to establish higher methylations (H3K4/36me3). Thus, methylation states are determined by the transcription rate. In summary, the first mechanism determines the location of methylations in the gene, while the second mechanism determines the methylation state.

Longitudinal Lower Airway Microbial Signatures of Acute Cellular Rejection in Lung Transplantation.

Rationale: Acute cellular rejection (ACR) after lung transplant is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. Objectives: To evaluate whether temporal changes in microbial signatures were associated with the development of ACR. Methods: We performed cross-sectional and longitudinal analyses (joint modeling of longitudinal and time-to-event data and trajectory comparisons) of 16S rRNA gene sequencing results derived from lung transplant recipient lower airway samples collected at multiple time points. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired 1 month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) than those with current or future (beyond 1 mo) ACR. However, a subgroup analysis of those who developed ACR beyond 1 month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared with baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in α-diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusions: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.

Kidney function and transplants in prune belly syndrome: a scoping review.

BACKGROUND: Children with prune belly syndrome (PBS) are at higher risk of developing kidney dysfunction and requiring kidney replacement therapy (KRT). While studies have described surgical and survival outcomes in these populations, there has yet to be a focused synthesis of evidence regarding kidney outcomes in this population. Here, the focus of this scoping review was to highlight knowledge gaps and report standards on kidney outcomes in PBS of all ages. METHODS: Following scoping review methodology, EMBASE, MEDLINE, and Scopus were searched for peer-reviewed literature that describe kidney outcomes in PBS. All studies with a broad set of kidney outcomes (such as kidney function measures, chronic kidney disease (CKD), KRT and associated outcomes) were included. Findings were summarized and qualitatively synthesized. RESULTS: Of the 436 unique records identified, 25 were included for synthesis. A total of 17 studies (441 patients) reported on kidney insufficiency outcomes, with an estimated prevalence of CKD ranging from 8 to 66%. A total of 15 studies (314 patients) described KRT, primary kidney transplant, and outcomes. Of these, the age for KRT ranged from 4 to 21 years, and graft survival ranged from 22 to 87% by last follow-up (range 1.3-27 years). CONCLUSIONS: There is significant variability in studies reporting kidney outcomes in PBS which limits meaningful synthesis. There is a need for future studies with comprehensive reporting of confounders and drivers for kidney insufficiency in PBS.

Fasting increases microbiome-based colonization resistance and reduces host inflammatory responses during an enteric bacterial infection.

Reducing food intake is a common host response to infection, yet it remains unclear whether fasting is detrimental or beneficial to an infected host. Despite the gastrointestinal tract being the primary site of nutrient uptake and a common route for infection, studies have yet to examine how fasting alters the host's response to an enteric infection. To test this, mice were fasted before and during oral infection with the invasive bacterium Salmonella enterica serovar Typhimurium. Fasting dramatically interrupted infection and subsequent gastroenteritis by suppressing Salmonella's SPI-1 virulence program, preventing invasion of the gut epithelium. Virulence suppression depended on the gut microbiota, as Salmonella's invasion of the epithelium proceeded in fasting gnotobiotic mice. Despite Salmonella's restored virulence within the intestines of gnotobiotic mice, fasting downregulated pro-inflammatory signaling, greatly reducing intestinal pathology. Our study highlights how food intake controls the complex relationship between host, pathogen and gut microbiota during an enteric infection.

Transition Readiness in Youth with Inflammatory Bowel Disease.

OBJECTIVES: To examine readiness of adolescents and young adults (AYAs) with inflammatory bowel disease (IBD) to transition to adult care. STUDY DESIGN: A cross-sectional multicenter study evaluating transition readiness in individuals with IBD 16-19 years old prospectively recruited from 8 Canadian IBD centers using the validated ON Taking Responsibility for Adolescent to Adult Care (ON TRAC) questionnaire. Secondary aims included (1) screening for depression and anxiety using the 8-item Personal Health Questionnaire Depression Scale and The Screen for Child Anxiety Related Emotional Disorders questionnaires, respectively; (2) evaluating the association between depression and anxiety with readiness and disease activity; and (3) subjectively evaluating AYA readiness based on physician and parent assessments. RESULTS: In total, 186 participants (139 adolescent, 47 young adult) were enrolled, mean age 17.4 years (SD, 0.87). ON TRAC scores determined that 26.6% of AYAs at pediatric and 40.4% at adult centers reached the threshold of readiness. On multivariable linear regression analysis age was positively (P = .001) and disease remission negatively (P = .03) associated with ON TRAC scores. No statistically significant differences were determined across centers. A significant percentage of AYAs reported moderate-to-severe depression (21.7%) and generalized anxiety (36%); however, neither were significantly associated with ON TRAC scores. Notably, physician and parental assessment of AYA readiness correlated poorly with ON TRAC scores (⍴ = 0.11, ⍴ = 0.24, respectively). CONCLUSIONS: Assessment of transition readiness in AYAs with IBD highlighted that a large proportion do not have adequate knowledge or behavior skills needed for transition to adult care. This study infers that readiness assessment tools are essential during transition to identify deficits in knowledge and behavior skills that could be specifically targeted by the youth, caregivers, and multidisciplinary team.

Surgical interhospital transfer mortality: national analysis.

BACKGROUND: Interhospital transfers of surgical patients are an independent risk factor for mortality. The Australian and New Zealand Audit of Surgical Mortality (ANZASM) aims to improve surgical care through assessment of all cases of surgical mortality. This study aimed to describe common clinical management issues that contributed to interhospital transfer patient mortality. METHODS: Data for all surgical patient mortality in Australia (except New South Wales) that underwent interhospital transfer between 1 January 2010 and 31 December 2019 were extracted from ANZASM. The surgeons' reports and assessors' evaluations were examined to identify clinical management issues. Thematic analysis was performed to develop pertinent themes and subthemes. RESULTS: Some 8679 patients were identified over the 10-year period. Of these, 2171 (25.0 per cent) had 3259 clinical management issues identified. Prominent themes were operative design (n = 466, 14.3 per cent), decision to operate (n = 425, 13.0 per cent), medical conditions (n = 344, 10.6 per cent), diagnosis (n = 326, 10 per cent), transfer (n = 293, 10.0 per cent), intraoperative issues (n = 278, 8.5 per cent), inadequate assessment (n = 238, 7.3 per cent), communication (n = 224, 6.9 per cent), delay in recognizing complications (n = 180, 5.5 per cent), coagulopathy (n = 151, 4.6 per cent), insufficient monitoring (n = 127, 3.9 per cent), infection (n = 107, 3.3 per cent), and hospital resources (n = 100, 3.1 per cent). Assessors considered 58.4 per cent of clinical management issues (n = 1903) probably or definitely preventable. CONCLUSION: This study identified 13 themes of potentially avoidable management issues present in surgical mortality following interhospital transfers. Quality-improvement initiatives targeting these areas may improve surgical patient outcomes.

Lung Transplantation for Primary Ciliary Dyskinesia and Kartagener Syndrome: A Multicenter Study.

Primary ciliary dyskinesia, with or without situs abnormalities, is a rare lung disease that can lead to an irreversible lung damage that may progress to respiratory failure. Lung transplant can be considered in end-stage disease. This study describes the outcomes of the largest lung transplant population for PCD and for PCD with situs abnormalities, also identified as Kartagener's syndrome. Retrospectively collected data of 36 patients who underwent lung transplantation for PCD from 1995 to 2020 with or without SA as part of the European Society of Thoracic Surgeons Lung Transplantation Working Group on rare diseases. Primary outcomes of interest included survival and freedom from chronic lung allograft dysfunction. Secondary outcomes included primary graft dysfunction within 72 h and the rate of rejection ≥A2 within the first year. Among PCD recipients with and without SA, the mean overall and CLAD-free survival were 5.9 and 5.2 years with no significant differences between groups in terms of time to CLAD (HR: 0.92, 95% CI: 0.27-3.14, p = 0.894) or mortality (HR: 0.45, 95% CI: 0.14-1.43, p = 0.178). Postoperative rates of PGD were comparable between groups; rejection grades ≥A2 on first biopsy or within the first year was more common in patients with SA. This study provides a valuable insight on international practices of lung transplantation in patients with PCD. Lung transplantation is an acceptable treatment option in this population.

Adenoid cystic carcinoma presenting as a midpalatal nodular mass with slow growth and long evolution: a case report with review of differential diagnosis.

Adenoid cystic carcinoma is an aggressive but slow-growing salivary gland tumor most commonly appearing in the palate. Though it is well recognized that this tumor has a slow-growing course, a clinical presentation of 10 years is uncommon. This article presents a case of a midpalatal nodular mass with a reported history of 10 years. The patient did not seek evaluation due to its small and asymptomatic clinical presentation, but an incisional biopsy later revealed the palatal nodular mass to be adenoid cystic carcinoma. The patient underwent surgical resection of the mass followed by adjuvant radiation therapy. This case report highlights the importance of prompt biopsy of a pathologic lesion despite an indolent history and benign clinical presentation. The various clinical differential diagnoses for a palatal nodular mass are also discussed.

Mitigation of nontuberculous mycobacteria in hospital water: challenges for infection prevention.

PURPOSE OF REVIEW: The purpose of this review is to summarize recent literature on nontuberculous mycobacteria in water of healthcare systems. Despite improvement in identification techniques and emergence of infection prevention and control programs, nontuberculous mycobacteria remain present in hospital water systems, causing outbreaks and pseudo-outbreaks in healthcare settings. RECENT FINDINGS: Waterborne outbreaks and pseudo-outbreaks of nontuberculous mycobacteria continue to affect hospitals. Improvements in methods of identification and investigation, including MALDI-TOF and whole genome sequencing with evaluation of single nucleotide polymorphisms, have been used successfully in outbreak and pseudo-outbreak investigations. Recent studies have shown control of outbreaks in immunocompromised patients through the use of sterile water for consumption, as well as control of pseudo-outbreaks by using sterile water for procedures. Construction activities have been implicated in outbreaks and pseudo-outbreaks of nontuberculous mycobacteria. Water management programs are now required by the Joint Commission, which will likely improve water risk mitigation. SUMMARY: Improvement in detection and identification of nontuberculous mycobacteria has led to increasing recognition of waterborne outbreaks and pseudo-outbreaks. Water management programs are of vital importance in infection prevention.

Blood Coagulation Factor Fibrinogen in Tumor Pathogenesis of Central Nervous System B-Cell Lymphoma.

Central nervous system (CNS) lymphoma is an extranodal non-Hodgkin B-cell lymphoma characterized by malignant lymph tissue arising in the brain or spinal cord, associated with inflammation and blood-brain barrier (BBB) disruption. Although BBB disruption is known to occur in patients with CNS lymphoma, a direct link between these two has not been shown. Herein, abundant deposition of the blood coagulation protein fibrinogen around B-cell lymphoma was detected in CNS lymphoma patients and in the CNS parenchyma in an orthotopic mouse model. Functional enrichment analysis of unbiased cerebrospinal fluid proteomics of CNS B-cell lymphoma patients showed that coagulation protein networks were highly connected with tumor-associated biological signaling pathways. In vivo two-photon imaging demonstrated that lymphoma growth was associated with BBB disruption, and in vitro experiments identified a role for fibrinogen in promoting lymphoma cell adhesion. Overall, these results identify perivascular lymphoma clustering at sites of fibrinogen deposition, and suggest that fibrinogen may be a target for pharmacologic intervention in metastatic B-cell lymphoma associated with BBB disruption.

Multi-institutional Validation of Improved Vesicoureteral Reflux Assessment With Simple and Machine Learning Approaches.

PURPOSE: Vesicoureteral reflux grading from voiding cystourethrograms is highly subjective with low reliability. We aimed to demonstrate improved reliability for vesicoureteral reflux grading with simple and machine learning approaches using ureteral tortuosity and dilatation on voiding cystourethrograms. MATERIALS AND METHODS: Voiding cystourethrograms were collected from our institution for training and 5 external data sets for validation. Each voiding cystourethrogram was graded by 5-7 raters to determine a consensus vesicoureteral reflux grade label and inter- and intra-rater reliability was assessed. Each voiding cystourethrogram was assessed for 4 features: ureteral tortuosity, proximal, distal, and maximum ureteral dilatation. The labels were then assigned to the combination of the 4 features. A machine learning-based model, qVUR, was trained to predict vesicoureteral reflux grade from these features and model performance was assessed by AUROC (area under the receiver-operator-characteristic). RESULTS: A total of 1,492 kidneys and ureters were collected from voiding cystourethrograms resulting in a total of 8,230 independent gradings. The internal inter-rater reliability for vesicoureteral reflux grading was 0.44 with a median percent agreement of 0.71 and low intra-rater reliability. Higher values for each feature were associated with higher vesicoureteral reflux grade. qVUR performed with an accuracy of 0.62 (AUROC=0.84) with stable performance across all external data sets. The model improved vesicoureteral reflux grade reliability by 3.6-fold compared to traditional grading (P < .001). CONCLUSIONS: In a large pediatric population from multiple institutions, we show that machine learning-based assessment for vesicoureteral reflux improves reliability compared to current grading methods. qVUR is generalizable and robust with similar accuracy to clinicians but the added prognostic value of quantitative measures warrants further study.

Risk factors associated with long-term mortality and complications after thoracoabdominal aortic aneurysm repair.

OBJECTIVE: We sought to determine the risk factors associated with late mortality or complications (thoracoabdominal aortic aneurysm [TAAA] life-altering events [TALE]: a composite of mortality, permanent paraplegia, permanent dialysis, and stroke) for patients who had undergone endovascular or open TAAA repair. METHODS: We performed a population-based study of patients who had undergone TAAA repair in Ontario, Canada, from 2006 to 2017. The association of baseline risk factors with mortality and complications after repair was examined using Cox hazards models with hospital-specific random effects. The survival of patients who had undergone TAAA repair was compared with that of controls without TAAAs. The two groups were matched by age, sex, area of residence, and average annual household income. The type of repair (endovascular vs open) was included in all models. RESULTS: We identified 664 adults (mean age, 69.3 ± 10.6 years; 71% men) who had undergone TAAA repair. At 5 and 8 years, survival was 55.0% (95% confidence interval [CI], 49.8%-60.1%) and 44.6% (95% CI, 40.4%-49.6%) for patients who had undergone TAAA repair vs 85.6% (95% CI, 83.9%-87.1%) and 76.3% (95% CI, 73.8%-78.8%) for the control population, respectively (hazard ratio [HR], 1.97; 95% CI, 1.67-2.32; P < .01). For the TAAA group, freedom from TALE was 49.2% (95% CI, 44.7%-53.7%) and 37.3% (95% CI, 33.1%-42.4%) at 5 and 8 years of follow-up, respectively. On multivariable analysis, the risk factors associated with mortality during follow-up included older age (HR, 1.21 per 5-year increase; 95% CI, 1.13-1.28), peripheral artery disease (HR, 1.46; 95% CI, 1.03-2.09), hypertension (HR, 1.58; 95% CI, 1.03-2.43), congestive heart failure (HR, 1.78; 95% CI, 1.34-2.36), and urgent procedures (HR, 2.27; 95% CI, 1.74-3.00). A lower rate of death was observed for those with previous coronary revascularization (HR, 0.63; 95% CI, 0.41-0.96) and those who had undergone repair at high-volume institutions (>60 TAAA repairs during the study period; HR, 0.71; 95% CI, 0.55-0.91). Older age, chronic kidney disease, congestive heart failure, and urgent procedures were associated with a higher rate of TALE. The type of repair (endovascular vs open) was not associated with mortality or TALE. CONCLUSIONS: TAAA repair was associated with reduced long-term survival compared with the general population, regardless of the mode of treatment. Urgent or emergent repair was the most profound risk factor for late adverse events. The type of repair (endovascular vs open) was not a predictor of long-term death or complications. Previous coronary revascularization and treatment performed at a high-volume institution were associated with improved late outcomes for patients undergoing TAAA repair.

One-year immunologic outcomes of lung transplantation utilizing hepatitis C-viremic donors.

Little is known about the effects of hepatitis C viremia on immunologic outcomes in the era of direct-acting antivirals. We conducted a prospective, single-arm trial of lung transplantation from hepatitis C-infected donors into hepatitis C-naïve recipients (n = 21). Recipients were initiated on glecaprevir-pibrentasvir immediately post-transplant and were continued on therapy for a total of 8 weeks. A control group of recipients of hepatitis C-negative lungs were matched 1:1 on baseline variables (n = 21). The primary outcome was the frequency of acute cellular rejection over 1-year post-transplant. Treatment with glecaprevir-pibrentasvir was well tolerated and resulted in viremia clearance after a median of 16 days of therapy (IQR 10-24 days). At one year, there was no difference in incidence of acute cellular rejection (71.4% vs. 85.7%, P = .17) or rejection requiring treatment (33.3% vs. 57.1%, P = .12). Mean cumulative acute rejection scores were similar between groups (.46 [SD ± .53] vs. .52 [SD ± .37], P = .67). Receipt of HCV+ organs was not associated with acute rejection on unadjusted Cox regression analysis (HR .55, 95% CI .28-1.11, P = .09), or when adjusted for risk factors known to be associated with acute rejection (HR .57, 95% CI .27-1.21, P = .14). Utilization of hepatitis C infected lungs with immediate treatment leads to equivalent immunologic outcomes at 1 year.

Code-free machine learning for object detection in surgical video: a benchmarking, feasibility, and cost study.

OBJECTIVE: While the utilization of machine learning (ML) for data analysis typically requires significant technical expertise, novel platforms can deploy ML methods without requiring the user to have any coding experience (termed AutoML). The potential for these methods to be applied to neurosurgical video and surgical data science is unknown. METHODS: AutoML, a code-free ML (CFML) system, was used to identify surgical instruments contained within each frame of endoscopic, endonasal intraoperative video obtained from a previously validated internal carotid injury training exercise performed on a high-fidelity cadaver model. Instrument-detection performances using CFML were compared with two state-of-the-art ML models built using the Python coding language on the same intraoperative video data set. RESULTS: The CFML system successfully ingested surgical video without the use of any code. A total of 31,443 images were used to develop this model; 27,223 images were uploaded for training, 2292 images for validation, and 1928 images for testing. The mean average precision on the test set across all instruments was 0.708. The CFML model outperformed two standard object detection networks, RetinaNet and YOLOv3, which had mean average precisions of 0.669 and 0.527, respectively, in analyzing the same data set. Significant advantages to the CFML system included ease of use, relatively low cost, displays of true/false positives and negatives in a user-friendly interface, and the ability to deploy models for further analysis with ease. Significant drawbacks of the CFML model included an inability to view the structure of the trained model, an inability to update the ML model once trained with new examples, and the inability for robust downstream analysis of model performance and error modes. CONCLUSIONS: This first report describes the baseline performance of CFML in an object detection task using a publicly available surgical video data set as a test bed. Compared with standard, code-based object detection networks, CFML exceeded performance standards. This finding is encouraging for surgeon-scientists seeking to perform object detection tasks to answer clinical questions, perform quality improvement, and develop novel research ideas. The limited interpretability and customization of CFML models remain ongoing challenges. With the further development of code-free platforms, CFML will become increasingly important across biomedical research. Using CFML, surgeons without significant coding experience can perform exploratory ML analyses rapidly and efficiently.

Geographical distribution of authorship for leading cardiothoracic surgery journals.

BACKGROUND: Evolution of surgical practice is influenced by publications in the leading journals of that field. If the authorship of a publication lacks geographical diversity, this could create bias and limit generalizability of the evidence. Accordingly, we conducted a geographical analysis of the leading Cardiothoracic Surgery journals worldwide. METHODS: Using 2020 Impact Factor, we searched the leading Cardiothoracic Surgery journals over the past decade. Only original articles were included. Data regarding first, second and last authors were extracted from every article. From this, we analysed country of affiliation, highest academic degree obtained and author location by metropolitan or rural setting. RESULTS: A total of 12,706 original articles were published in the top 5 ranked Cardiothoracic journals between 2011 and 2020. Authors originated from 69 countries, with the majority being from North America and Western Europe. The United States was the most common country of affiliation (42.8%) in all five journals, with New York City the most prominent city. A total of  63.7% of the authorship originated from large metropolitan areas (estimated as population greater than 500,000 residents), and the most common degrees obtained by authors were MD and PhD. CONCLUSION: The prominent Cardiothoracic authorship is predominantly located in Western countries, most commonly large metropolitan centers in the United States. This raises questions as to whether the literature adequately reflects populations in other geographical areas such as the continents of South America and Africa and rural settings. Leading journals should consider policies which encourage publication by authors from geographical locations that are underrepresented globally.

Endovascular thrombectomy for large vessel occlusion acute ischemic stroke after cardiac surgery.

INTRODUCTION: Acute ischemic stroke (AIS) can be a catastrophic complication of cardiac surgery previously without effective treatment. Endovascular thrombectomy (EVT) is a potentially life-saving intervention. We examined patients at our institution who had EVT to treat AIS post cardiac surgery. METHODS: We retrospectively reviewed a stroke database from January 1, 2016 to October 31, 2021 to identify patients who had undergone EVT to treat AIS following cardiac surgery. Demographic data, operation type, stroke severity, imaging features, management and outcomes (mortality and modified Rankin Score (mRS)) were assessed. RESULTS: Of 5022 consecutive patients with AIS, 870 underwent EVT. Seven patients (0.8%) had EVT following cardiac surgery. Operations varied: two coronary artery bypass grafting (CABG), two transcatheter AVR, one redo surgical aortic valve replacement (AVR), one mitral valve repair and one patient with combined aortic and mitral valve replacements and CABG. Meantime postsurgery to stroke symptoms onset was 3 days (range 0-9 days). Median NIHSS was 26 (range 10-32). Five patients had middle cerebral artery occlusion and two internal carotid artery (n = 2). Median time between onset of symptoms and recanalization was 157 min (range 97-263). Two patients received Intra-arterial Thrombolysis. All patients survived and were discharged to another hospital (n = 3), home (n = 2), or rehabilitation facility (n = 2). Median 3-month mRS was 3 (range 0-6). CONCLUSION: We report the largest case series of EVT after cardiac surgery. EVT can be associated with excellent outcomes in these patients. Close neurological monitoring postoperatively to identify patients who may benefit from intervention is key.

Trends in the Extracorporeal Membrane Oxygenation Literature: A Bibliometric Analysis in the COVID-19 Era.

Extracorporeal Membrane Oxygenation (ECMO) was first used in the 1970s. Its use is increasingly common in critical care and perioperative settings and has gained newfound prominence during COVID-19. To guide future research, we conducted a bibliometric analysis of ECMO literature. Thomson Reuters Web of Science was searched to March 7, 2021. Articles were ranked by total number of citations. Data was extracted from the 100 most cited papers relevant to ECMO for study design, topic, author, year, and institution. Journal impact factor for 2019 and Eigenfactor scores were also recorded. Our search retrieved a total of 18,802 articles. Median number of citations for the top 100 articles was 220 (range 157-1,819). These were published in 34 journals, with first authors originating from 15 countries. The Annals of Thoracic Surgery had the highest number of articles (n = 9) while Lancet publications had the most citations (n = 3,191). Use of ECMO was most commonly observed in cardiogenic shock or acute respiratory distress syndrome. United States had the greatest article output (n = 49). With 10 publications, 2013 was the most prolific year. Using linear regression, when controlled for time since publication, there was no statistically significant relationship between 2019 journal impact factor and number of article citations (p = .09). Top articles in the ECMO literature are of considerable impact and quality. As the United States produced the bulk of the prominent evidence base, and most data were regarding respiratory issues, outsized advances in ECMO may be possible within the United States during the COVID-19 era.

DR-SIP: protocols for higher order structure modeling with distance restraints- and cyclic symmetry-imposed packing.

MOTIVATION: Quaternary structure determination for transmembrane/soluble proteins requires a reliable computational protocol that leverages observed distance restraints and/or cyclic symmetry (Cn symmetry) found in most homo-oligomeric transmembrane proteins. RESULTS: We survey 118 X-ray crystallographically solved structures of homo-oligomeric transmembrane proteins (HoTPs) and find that ∼97% are Cn symmetric. Given the prevalence of Cn symmetric HoTPs and the benefits of incorporating geometry restraints in aiding quaternary structure determination, we introduce two new filters, the distance-restraints (DR) and the Symmetry-Imposed Packing (SIP) filters. SIP relies on a new method that can rebuild the closest ideal Cn symmetric complex from docking poses containing a homo-dimer without prior knowledge of the number (n) of monomers. Using only the geometrical filter, SIP, near-native poses of 7 HoTPs in their monomeric states can be correctly identified in the top-10 for 71% of all cases, or 29% among 31 HoTP structures obtained through homology modeling, while ZDOCK alone returns 14 and 3%, respectively. When the n is given, the optional n-mer filter is applied with SIP and returns the near-native poses for 76% of the test set within the top-10, outperforming M-ZDOCK's 55% and Sam's 47%. While applying only SIP to three HoTPs that comes with distance restraints, we found the near-native poses were ranked 1st, 1st and 10th among 54 000 possible decoys. The results are further improved to 1st, 1st and 3rd when both DR and SIP filters are used. By applying only DR, a soluble system with distance restraints is recovered at the 1st-ranked pose. AVAILABILITY AND IMPLEMENTATION: https://github.com/capslockwizard/drsip. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Cross-Sectional Analysis of Quality of Life in Pediatric Patients with Inflammatory Bowel Disease in British Columbia, Canada.

OBJECTIVES: To evaluate quality of life (QoL) in a large cohort of pediatric patients with inflammatory bowel disease (IBD) and to identify the clinical factors that influence QoL. STUDY DESIGN: This cross-sectional study analyzes a quality improvement initiative in 351 pediatric patients with IBD in British Columbia, Canada using the self-reported Pediatric Quality of Life Inventory (PedsQL) 4.0 generic scale. The questionnaire was completed at outpatient clinic and biologic infusion appointments. Statistical analysis included the t test, ANOVA, and multilinear regressions to evaluate the relationships between clinical factors and QoL. RESULTS: Mean (SE) QoL scores (79.95 [0.84]) fell between previously described healthy and chronically ill populations. Disease activity was the most significant predictor of QoL, with patients in remission scoring similar (84.42 [0.87]) to well established healthy norms, and those with moderately or severely active disease having some of the lowest published PedsQL scores (63.13 [3.27]), lower than most other chronic pediatric conditions. Twenty-five patients with moderately or severely active disease at the time of survey completion had follow-up surveys identified 1 year later and had a significant improvement of both their disease activity (P < .005) and their PedsQL scores (follow-up survey mean 76.13 [3.11]). Additional clinical factors independently associated with poor QoL were school nonattendance (15.5% decrease in QoL, P < .001), immune-modulator selection (methotrexate conferring a 9.5% lower mean QoL score than azathioprine, P = .005), and female gender (P = .031). CONCLUSION: Pediatric patients with IBD experience a QoL significantly impacted by multiple clinical factors including current severity of IBD symptoms.