Obesity increases the risk of major wound complications following pelvic resection for bone sarcoma.

BACKGROUND: Given the paucity of data, the objective of this study is to evaluate the association between obesity and major wound complications following pelvic bone sarcoma surgery specifically. METHODS: Patients who underwent pelvic resection for bone sarcoma from 2005 to 2021 with a minimum 6-month follow-up were reviewed. Patients with benign tumors, primary soft tissue sarcomas, local recurrence at presentation, pelvic metastatic disease, and underweight patients were excluded. A major wound complication was defined as the need for a secondary debridement procedure. Differences in baseline demographics, surgical factors, postoperative complications, and functional outcomes were compared between obese and nonobese patients. A multivariate logistic regression was performed to identify independent risk factors for major wound complications, and a Kaplan-Meier analysis to estimate overall survival between both groups. RESULTS: Of the 93 included patients, 21 were obese (body mass index ≥ 30 kg/m2). The obesity group had a significantly higher rate of major wound complication (52% vs. 26%, p = 0.034) and a lower Toronto Extremity Salvage Score at 1-year postoperatively (47.5 vs. 71.4, p = 0.025). Obesity was the only independent risk factor in the multivariate analysis. No differences in overall survival were demonstrated between groups. CONCLUSIONS: Obesity is a significant risk factor for major wound complications in pelvic bone sarcoma treatment. This highlights the importance of careful perioperative optimization and wound management.

COVID-KOP: integrating emerging COVID-19 data with the ROBOKOP database.

SUMMARY: In response to the COVID-19 pandemic, we established COVID-KOP, a new knowledgebase integrating the existing Reasoning Over Biomedical Objects linked in Knowledge Oriented Pathways (ROBOKOP) biomedical knowledge graph with information from recent biomedical literature on COVID-19 annotated in the CORD-19 collection. COVID-KOP can be used effectively to generate new hypotheses concerning repurposing of known drugs and clinical drug candidates against COVID-19 by establishing respective confirmatory pathways of drug action. AVAILABILITY AND IMPLEMENTATION: COVID-KOP is freely accessible at https://covidkop.renci.org/. For code and instructions for the original ROBOKOP, see: https://github.com/NCATS-Gamma/robokop.

ROBOKOP: an abstraction layer and user interface for knowledge graphs to support question answering.

SUMMARY: Knowledge graphs (KGs) are quickly becoming a common-place tool for storing relationships between entities from which higher-level reasoning can be conducted. KGs are typically stored in a graph-database format, and graph-database queries can be used to answer questions of interest that have been posed by users such as biomedical researchers. For simple queries, the inclusion of direct connections in the KG and the storage and analysis of query results are straightforward; however, for complex queries, these capabilities become exponentially more challenging with each increase in complexity of the query. For instance, one relatively complex query can yield a KG with hundreds of thousands of query results. Thus, the ability to efficiently query, store, rank and explore sub-graphs of a complex KG represents a major challenge to any effort designed to exploit the use of KGs for applications in biomedical research and other domains. We present Reasoning Over Biomedical Objects linked in Knowledge Oriented Pathways as an abstraction layer and user interface to more easily query KGs and store, rank and explore query results. AVAILABILITY AND IMPLEMENTATION: An instance of the ROBOKOP UI for exploration of the ROBOKOP Knowledge Graph can be found at http://robokop.renci.org. The ROBOKOP Knowledge Graph can be accessed at http://robokopkg.renci.org. Code and instructions for building and deploying ROBOKOP are available under the MIT open software license from https://github.com/NCATS-Gamma/robokop. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Cell-free expression of natively folded hydrophobins.

Hydrophobins are a family of cysteine-rich proteins unique to filamentous fungi. The proteins are produced in a soluble form but self-assemble into organised amphipathic layers at hydrophilic:hydrophobic interfaces. These layers contribute to transitions between wet and dry environments, spore dispersal and attachment to surfaces for growth and infection. Hydrophobins are characterised by four disulphide bonds that are critical to their structure and function. Thus, obtaining correctly folded, soluble and functional hydrophobins directly from bacterial recombinant expression is challenging and in most cases, initial denaturation from inclusion bodies followed by oxidative refolding are required to obtain folded proteins. Here, we report the use of cell-free expression with E. coli cell lysate to directly obtain natively folded hydrophobins. All six of the hydrophobins tested could be expressed after optimisation of redox conditions. For some hydrophobins, the inclusion of the disulfide isomerase DsbC further enhanced expression levels. We are able to achieve a yield of up to 1 mg of natively folded hydrophobin per mL of reaction. This has allowed the confirmation of the correct folding of hydrophobins with the use of 15N-cysteine and 15N-1H nuclear magnetic resonance experiments within 24 h of starting from plasmid stocks.

ROBOKOP KG and KGB: Integrated Knowledge Graphs from Federated Sources.

A proliferation of data sources has led to the notional existence of an implicit Knowledge Graph (KG) that contains vast amounts of biological knowledge contributed by distributed Application Programming Interfaces (APIs). However, challenges arise when integrating data across multiple APIs due to incompatible semantic types, identifier schemes, and data formats. We present ROBOKOP KG ( http://robokopkg.renci.org ), which is a KG that was initially built to support the open biomedical question-answering application, ROBOKOP (Reasoning Over Biomedical Objects linked in Knowledge-Oriented Pathways) ( http://robokop.renci.org ). Additionally, we present the ROBOKOP Knowledge Graph Builder (KGB), which constructs the KG and provides an extensible framework to handle graph query over and integration of federated data sources.

Vernakalant for cardioversion of recent-onset atrial fibrillation: a systematic review and meta-analysis.

AIMS: To evaluate the efficacy and safety of vernakalant for the cardioversion of atrial fibrillation (AF). METHODS AND RESULTS: We reviewed the literature for randomized trials that compared vernakalant to another drug or placebo in patients with AF of onset ≤7 days. We used a random-effects model to combine quantitative data and rated the quality of evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation). From 441 total citations in MEDLINE, EMBASE, and CENTRAL (December 2018), we identified nine trials evaluating 1358 participants. Six trials compared vernakalant to placebo, two trials compared vernakalant to ibutilide, and one trial compared vernakalant to amiodarone. We found significant methodological bias in four trials. For conversion within 90 min, vernakalant was superior to placebo [50% conversion, risk ratio (RR) 5.15; 95% confidence interval (CI); 2.24-11.84, I2 = 91%], whereas we found no significant difference in conversion when vernakalant was compared with an active drug (56% vs. 24% conversion, RR 2.40; 95% CI 0.76-7.58, I2 = 94). Sinus rhythm was maintained at 24 h in 85% (95% CI 80-88%) of patients who converted acutely with vernakalant. Overall, we judged the quality of evidence for efficacy to be low based on inconsistency and suspected publication bias. There was no significant difference in the risk of significant adverse events between vernakalant and comparator (RR 0.95; 95% CI 0.70-1.28, I2 = 0, moderate quality evidence). Vernakalant is safe and effective for rapid and durable restoration of sinus rhythm in patients with recent-onset AF. CONCLUSION: Vernakalant should be a first line option for the pharmacological cardioversion of patients with haemodynamically stable recent-onset AF without severe structural heart disease.

Sequential central retinal artery occlusions associated with cryoglobulinemia.

BACKGROUND: Cryoglobulinemia, the presence of serum cryoglobulins which are immunoglobulins or complement components that precipitate at temperatures below 37 °C, commonly present with cutaneous manifestations initially, but are more rarely associated with ocular manifestations. To our knowledge, we report the first case of a patient presenting with sequential central retinal artery occlusion (CRAO) associated with cryoglobulinemia. CASE PRESENTATION: A 69-year-old female with a history of indolent B-cell lymphoma associated cryoglobulinemia, treated hepatitis B infection and CRAO in the left eye presented with acute vision loss and diffuse retinal whitening with a cherry red spot in her right eye, suggestive of sequential CRAO. Laboratory studies revealed a cryocrit of 55% (normal < 1%), elevated titres of cryoglobulin IgG at 1.98 g/L and cryoglobulin IgM at 3.78 g/L (normal < 0.3 g/L)9, and elevated kappa free light chain at 283.5 mg/L (normal < 0.06 g/L). Such elevated tires of cryoglobulins in the context of the patient's CRAO raised suspicion of cryoglobulinemia associated CRAO. The patient was promptly referred to rheumatology and oncology and was admitted for treatment including intravenous methylprednisone, rituximab and bendamustine chemotherapy. CONCLUSIONS: We report a patient with a complex medical history presenting with significant vision loss due to a sequential CRAO likely associated with cryoglobulinemia. Although a direct relationship between cryoglobulinemia and CRAO cannot be confirmed in this case, it highlights the importance of considering cryoglobulinemia in high-risk patients with prior history of hematological malignancy or chronic hepatitis infection.

Utilization and barriers to eye care following school-wide pediatric vision screening.

OBJECTIVE: In August 2018, Ontario introduced the Child Visual Health and Vision Screening Protocol outlining school-based senior kindergarten (aged 4-6 years) vision screening. We determine the prevalence of children at risk based on screening in an Ontario community and follow up to determine resource utilization after screening. METHODS: Vision screening data (HOTV, Randot, Autorefractor) from 41 schools (1127 children) were collected for the 2018-2019 and 2019-2020 school years. Phone follow-up was conducted 1-1.5 years after screening to determine whether an optometry visit occurred, if glasses were prescribed, and potential barriers to accessing eye care. Independent t tests were used to compare time to follow-up between groups, and χ2 testing was used for associations between material and social deprivation. RESULTS: Overall screening resulted in a 32.2% referral rate within our region. Of the referred children who responded, the rate of seeking out eye care was 69.9% (n = 64), and 65.2% of these visits were prompted specifically by vision screening, and 34.4% of referred children respondents were prescribed glasses. There was a significant relationship between receiving a referral and living in a more materially deprived (p = 0.001) and a more socially deprived area (p = 0.006). The most frequently reported barriers were related to insufficient insurance coverage for eye care or glasses, COVID-19-related difficulties, and scheduling conflicts. CONCLUSION: Our vision screening program identified and referred more than one third of children screened for follow-up eye examinations, with children in more deprived neighbourhoods being more frequently referred. Around two thirds of referred children sought care, and one third were prescribed glasses in the follow-up sample.

Potential Role for Non-Salvage Procedures in the Treatment of Kienböck Disease Stage IV: A Systematic Review.

BACKGROUND: The purpose of this systematic review is to identify whether non-salvage procedures can provide satisfactory and acceptable outcomes in Lichtman stage IV disease. METHODS: The MEDLINE, Embase, and Cochrane databases were systematically searched for English publications between 1989 and 2019 that reported stage IV-specific primary treatment outcomes. Revisions and skeletally immature patients were excluded. Data extracted were patient demographics, pain scores, range of motion (ROM), grip strength, and patient-reported outcome measures (PROMs). The results were pooled into 3 categories: conservative management, non-salvage, and salvage procedures. RESULTS: Data from 24 studies (n = 114 patients) were extracted. Compared with conservative management and non-salvage treatment (joint-leveling radial osteotomies, lunate reconstruction), salvage procedures (intercarpal and radiocarpal arthrodesis, proximal row carpectomy, total wrist arthroplasty) showed significantly decreased ROM in flexion-extension arc of motion (89° vs 95° vs 73°, respectively, P = .0001) and no significant differences in grip strength as a percentage of the contralateral side (83% vs 86% vs 79%, respectively, P = .28). All reported treatments provided pain relief, ability to return to previous occupations, and variable PROMs. CONCLUSIONS: In young, active, and labor-intensive patients, motion-preserving, non-salvage options may be worth trialing as they do not preclude future salvage options.

Relationship Between Macular Thickness and Visual Acuity in the Treatment of Diabetic Macular Edema With Anti-VEGF Therapy: Systematic Review.

Purpose: To examine the relationship between central macular thickness (CMT) measured by optical coherence tomography (OCT) and visual acuity (VA) in patients with center-involving diabetic macular edema (DME) receiving antivascular endothelial growth factor (anti-VEGF) treatment. Methods: Peer-reviewed articles from 2016 to 2020 reporting intravitreal injections of bevacizumab, ranibizumab, or aflibercept that provided data on pretreatment (baseline) and final retinal thickness (CMT) and visual acuity (VA) were identified. The relationship between relative changes was assessed via a linear random-effects regression model controlling for treatment group. Results: No significant association between the logarithm of the minimum angle of resolution (logMAR) VA and CMT was found in 41 eligible studies evaluating 2667 eyes. The observed effect estimate was a 0.12 increase (95% CI, -0.124 to 2.47) in logMAR VA per 100 µm reduction in CMT after treatment change. There were no significant differences in logMAR VA between the anti-VEGF treatment groups. Conclusions: There was no statistically significant relationship between the change in logMAR VA and change in CMT as well as no significant effect of the type of anti-VEGF treatment on the change in logMAR VA. Although OCT analysis, including measurements of CMT, will continue to be an integral part of the management of DME, further exploration is needed on additional anatomic factors that might contribute to visual outcomes.

Intraobserver and Interobserver Reliability of the Snyder and Expanded SLAP Classification System: A Video Study.

Background: Superior labral anterior and posterior (SLAP) tears are a common finding in overhead athletes. The original classification system produced by Snyder in 1990 contained 4 types of SLAP tears and was later expanded to 10 types. The classification has been challenging because of inconsistencies between surgeons making diagnoses and treatments based on the diagnosis. Furthermore, patient factors-such as age and sports played-affect the treatment algorithms, even across similarly classified SLAP tears. Purpose: To (1) assess the interobserver and intraobserver reliability of the Snyder and expanded SLAP (ESLAP) classification systems and (2) determine the consistency of treatment for a given SLAP tear depending on different clinical scenarios. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: A total of 20 arthroscopic surgical videos and magnetic resonance imaging scans of patients with SLAP tears were sent to 20 orthopaedic sports medicine surgeons at various stages of training. Surgeons were asked to identify the type of SLAP tear using the Snyder and ESLAP classifications. Surgeons were then asked to determine the treatment for a SLAP tear using 4 clinical scenarios: (1) in the throwing arm of an 18-year-old pitcher; (2) in the dominant arm of an 18-year-old overhead athlete; (3) a 35-year-old overhead athlete; (4) or a 50-year-old overhead athlete. Responses were recorded, and the cases were shuffled and sent back 6 weeks after the initial responses. Results were then analyzed using the Fleiss kappa coefficient (κ) to determine interobserver and intraobserver degrees of agreement. Results: There was moderate intraobserver reliability in both the Snyder and ESLAP classifications (κ = 0.52) and fair interobserver reliability for both classification systems (Snyder, κ = 0.31; ESLAP, κ = 0.30; P < .0001) among all surgeons. Additionally, there was only fair agreement (κ = 0.30; P < .0001) for the treatment modalities chosen by the reviewers for each case. Conclusion: This study demonstrated that SLAP tears remain a challenging problem for orthopaedic surgeons in diagnostics and treatment plans. Therefore, care should be taken in the preoperative discussion with the patient to consider all the possible treatment options because this may affect the postoperative recovery period and patient expectations.

Tempering Expectations on the Medical Artificial Intelligence Revolution: The Medical Trainee Viewpoint.

The rapid development of artificial intelligence (AI) in medicine has resulted in an increased number of applications deployed in clinical trials. AI tools have been developed with goals of improving diagnostic accuracy, workflow efficiency through automation, and discovery of novel features in clinical data. There is subsequent concern on the role of AI in replacing existing tasks traditionally entrusted to physicians. This has implications for medical trainees who may make decisions based on the perception of how disruptive AI may be to their future career. This commentary discusses current barriers to AI adoption to moderate concerns of the role of AI in the clinical setting, particularly as a standalone tool that replaces physicians. Technical limitations of AI include generalizability of performance and deficits in existing infrastructure to accommodate data, both of which are less obvious in pilot studies, where high performance is achieved in a controlled data processing environment. Economic limitations include rigorous regulatory requirements to deploy medical devices safely, particularly if AI is to replace human decision-making. Ethical guidelines are also required in the event of dysfunction to identify responsibility of the developer of the tool, health care authority, and patient. The consequences are apparent when identifying the scope of existing AI tools, most of which aim to be physician assisting rather than a physician replacement. The combination of the limitations will delay the onset of ubiquitous AI tools that perform standalone clinical tasks. The role of the physician likely remains paramount to clinical decision-making in the near future.

Measuring anion binding at biomembrane interfaces.

The quantification of anion binding by molecular receptors within lipid bilayers remains challenging. Here we measure anion binding in lipid bilayers by creating a fluorescent macrocycle featuring a strong sulfate affinity. We find the determinants of anion binding in lipid bilayers to be different from those expected that govern anion binding in solution. Charge-dense anions H2PO4- and Cl- that prevail in dimethyl sulfoxide fail to bind to the macrocycle in lipids. In stark contrast, ClO4- and I- that hardly bind in dimethyl sulfoxide show surprisingly significant affinities for the macrocycle in lipids. We reveal a lipid bilayer anion binding principle that depends on anion polarisability and bilayer penetration depth of complexes leading to unexpected advantages of charge-diffuse anions. These insights enhance our understanding of how biological systems select anions and guide the design of functional molecular systems operating at biomembrane interfaces.

Intraosseous Lipoma Mimicking Periapical Lesion: A Rare Presentation.

Lipoma is one of the benign soft-tissue tumors in the adipose tissue. Oral lipomas comprise 1%-5% of benign oral tumors. They are slow-growing, soft, asymptomatic, solitary tumors. In this case report, a 45-year-old female patient having swelling on the upper right arch for 2 months has been reported. Clinically, the right upper second premolar and first molar were grossly carious, with diffuse swelling on the adjacent vestibule. A provisional diagnosis of the periapical abscess was rendered. Radiological evaluation and routine blood tests were performed. After the tissue was obtained, following teeth extraction and socket curettage, it was sent for histopathological evaluation, and findings suggested intraoral intraosseous lipoma. Clinically, they are asymptomatic, and therefore, if it was not curetted and histopathologic evaluation not done, and only thought to be just a swelling or a periapical abscess, proper treatment could not have been established. This paper will surely bring out the importance of histopathology in routine dentistry and the role of histopathological evaluation of periapical soft tissues.

Insights from teaching artificial intelligence to medical students in Canada.

Clinical artificial intelligence (AI) applications are rapidly developing but existing medical school curricula provide limited teaching covering this area. Here we describe an AI training curriculum we developed and delivered to Canadian medical undergraduates and provide recommendations for future training.

Higher Mortality in Women After Coronary Artery Bypass: Meta-analysis and Bias Analysis of Confounding.

BACKGROUND: Some studies suggest that the observed higher mortality in women compared with men after coronary artery bypass grafting (CABG) is due to confounding. Our meta-analysis aimed to (1) summarize the effect of sex on mortality after CABG and (2) identify whether unmeasured confounding likely explains the apparent higher mortality in women. METHODS: We searched MEDLINE, Embase, and CENTRAL databases for studies examining sex and 30-day mortality after CABG. We used random-effects meta-analysis to estimate the summary odds ratio (OR) of mortality in women versus men using (1) unadjusted study results and (2) adjusted study results. Available confounders data from included studies were identified. Using the OR of measured confounders and the risk of death to inform unmeasured confounding effects, we performed bias analysis simulation to correct potential unmeasured confounding in the summary OR. RESULTS: From 7,138 retrieved studies, 112 were included (N = 5,008,262 patients); 25 studies reported adjusted OR (N = 770,450 patients). Overall 30-day mortality was 4.9% in women versus 3.3% in men. The unadjusted summary OR (1.81; 95% confidence interval, 1.72-1.91) and adjusted summary OR (1.40, 95% confidence interval, 1.35-1.45) demonstrated women had an increased risk for 30-day mortality compared with men. Simulations correcting for unmeasured confounding mostly ranged from 1.05 to 1.80, which supports a higher risk for death in women after CABG. CONCLUSIONS: The findings of this review suggest that confounding is unlikely to account for the increased risk for mortality in women after CABG and that biological factors have a causal effect.

Surgical Management and Rehabilitation of an Olecranon Fracture in a Patient with Thrombocytopenia-Absent Radii: A Case Report.

CASE: A 29-year-old right-hand dominant woman with thrombocytopenia-absent radii syndrome was surgically treated for a right olecranon fracture. Given her forearm deformity and short lever arm, a custom-modified corrective elbow flexion splint was used during rehabilitation. Radiographic union was achieved. Although functional outcome scores were similar to the ones previously reported in the general population, the patient had persistent extension contracture. CONCLUSION: Despite good functional outcomes, the patient had reduced range of motion. With severe limb deformity, the greatest challenge is to provide optimal rehabilitation protocols and individualized tools.

Idiopathic retinal arterial occlusive vasculitis in the setting of multiple arterial occlusions.

PURPOSE: We present a patient with vaso-occlusive retinal vasculitis to summarize this uncommon entity and review the clinical features and management challenges applicable to patients with retinal vasculitis. OBSERVATIONS: A 76-year-old male presented with sudden-onset severe central vision loss. On examination, vitreous hemorrhage, neovascularization of the optic nerve, peripheral segmental periphlebitis, vessel sclerosis, vascular sheathing, and retinal hemorrhages were observed, and a diagnosis of active vaso-occlusive retinal vasculitis was made. The patient then underwent a complete infectious, inflammatory, and neoplastic workup which returned negative. The patient was treated with locally with a sub-Tenon's injection of 40 mg triamcinolone on presentation and later with oral prednisone. At three-month follow-up, vision improved to 20/300 with regressing neovascularization and clearing of vitreous hemorrhage in the right eye (OD). CONCLUSIONS: Considering novel associations of occlusive retinal vasculitis, it is important to recognize that idiopathic occlusive retinal vasculitis, although uncommon, can occur and represents a prototypical disease form. It is imperative that these patients have a complete infectious, inflammatory, and neoplastic workup owing to the possible overlap of masquerade clinical signs and symptoms.

Antioxidants for the Treatment of Retinal Disease: Summary of Recent Evidence.

Retinal tissue is prone to oxidant burden and oxidative stress secondary to the generation of reactive oxygen species from high metabolic demand. The formation of reactive oxygen species occurs primarily from the mitochondrial respiratory chain as well as several enzymatic and oxidation reactions that occur in the neurosensory retina and retinal pigment epithelium. This oxidative stress has been implicated in the pathogenesis of several retinal diseases and the role of antioxidants as a therapeutic treatment shows promise in slowing the progression of certain diseases. The aim of this narrative review is to describe the mechanisms of retinal oxidative stress and summarize the current available evidence for antioxidants as a treatment for vitreoretinal disorders.

Evaluation of Splenic Artery Embolization Technique for Blunt Trauma.

INTRODUCTION: Evaluate outcomes and radiation exposure across different splenic artery embolization (SAE) techniques for splenic injuries secondary to blunt trauma. METHODS: This retrospective cohort study included patients 18 years of age or older who underwent SAE for splenic injury after blunt trauma from January 2011 to June 2019. RESULTS: Sixty patients underwent angiography for splenic injury after blunt traumatic injury. Forty-four patients were embolized. Seventeen patients underwent proximal SAE, and 23 underwent distal SAE. Four patients had a combination of proximal and distal SAE. Eleven patients had subsequent major complications requiring splenectomy. There was no significant difference in major complication rate when comparing proximal SAE 29.4% versus distal SAE 21.7%. No significant difference was noted across the two groups with respect to age or grade of injury. There was a statistically significant difference (P = 0.004) in fluoroscopy time between the proximal 10.1 ± 4.2 min and distal group 17.8 ± 8.7 min. No statically significant difference was found in major complications when comparing coil versus gel foam embolization. CONCLUSION: Proximal SAE is associated with a significantly lower fluoroscopy time (P = 0.004). Complication rates are similar after proximal and distal SAE. No significant difference was found in major complication rates comparing coil versus gel foam embolization. Minor complications more commonly occurred after proximal embolization with gel-foam.