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Glaucoma and age-related macular degeneration (AMD) are progressive retinal diseases characterized by increased oxidative stress, inflammation, and mitochondrial dysfunction. This review investigates the potential therapeutic benefits of NAD+ and niacin supplementation in managing glaucoma and AMD. A literature search was conducted encompassing keywords such as "niacin", "NAD", "glaucoma", "AMD", and "therapeutics". NAD+ depletion is associated with increased oxidative stress and mitochondrial dysfunction in glaucoma and AMD. Niacin, a precursor to NAD+, has shown promise in replenishing NAD+ levels, improving choroidal blood flow, and reducing oxidative damage. Animal studies in glaucoma models indicate that nicotinamide (NAM) supplementation preserves RGC density and function. Large-scale population-based studies indicate an inverse correlation between niacin intake and glaucoma prevalence, suggesting a preventative role. Randomized controlled trials assessing niacin supplementation showed significant improvements in visual field sensitivity and inner retinal function, with a dose-dependent relationship. In AMD, nicotinamide supplementation may improve rod cell function and protect against oxidative stress-induced damage. Cross-sectional studies reveal that individuals with AMD have a lower dietary intake of niacin. Further studies suggest niacin's role in improving choroidal blood flow and dilating retinal arterioles, potentially mitigating ischemic damage and oxidative stress in AMD. Beyond current management strategies, NAD+ and niacin supplementation may offer novel therapeutic avenues for glaucoma and AMD. Further research is warranted to elucidate their efficacy and safety in clinical settings.

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Suplementos Dietéticos , Glaucoma , Degeneración Macular , NAD , Niacina , Estrés Oxidativo , Humanos , Niacina/administración & dosificación , Niacina/uso terapéutico , Niacina/farmacología , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/prevención & control , NAD/metabolismo , Glaucoma/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Animales

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In this paper we demonstrate that Pt(ii) complexes can function as efficient transmembrane chloride transporters. A series of Pt(ii) metal complexes with urea-appended isoquinoline ligands were synthesised and operate via classical hydrogen bonding interactions rather than ligand exchange. A number of the complexes exhibited potent transmembrane chloride activity in vesicle studies, while also showing strong antiproliferative activity in cisplatin-resistant cell lines via induction of apoptosis and inhibition of intracellular ROS.

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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.

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Neoplasias Óseas , Obesidad , Huesos Pélvicos , Complicaciones Posoperatorias , Humanos , Femenino , Masculino , Neoplasias Óseas/cirugía , Neoplasias Óseas/mortalidad , Obesidad/complicaciones , Persona de Mediana Edad , Adulto , Factores de Riesgo , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Huesos Pélvicos/cirugía , Huesos Pélvicos/patología , Sarcoma/cirugía , Sarcoma/patología , Sarcoma/mortalidad , Estudios de Seguimiento , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/epidemiología , Adulto Joven , Pronóstico , Tasa de Supervivencia , Adolescente , Anciano

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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.

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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.

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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.

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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.

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COVID-19 , Optometría , Errores de Refracción , Selección Visual , Niño , Humanos , Selección Visual/métodos , Visión Ocular , Instituciones Académicas , Errores de Refracción/diagnóstico

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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.

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Hueso Semilunar , Osteonecrosis , Humanos , Articulación de la Muñeca/cirugía , Hueso Semilunar/cirugía , Osteonecrosis/cirugía , Resultado del Tratamiento , Dolor

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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.

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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.

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Dimetilsulfóxido , Membrana Dobles de Lípidos , Aniones/química , Membrana Dobles de Lípidos/química , Sulfatos

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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.

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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.

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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.

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Puente de Arteria Coronaria/métodos , Enfermedad de la Arteria Coronaria/cirugía , Complicaciones Posoperatorias/mortalidad , Medición de Riesgo/métodos , Puente de Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/mortalidad , Femenino , Salud Global , Humanos , Factores de Riesgo , Tasa de Supervivencia/tendencias

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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.

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Hiperpigmentación , Minociclina , Antibacterianos/efectos adversos , Humanos , Hiperpigmentación/inducido químicamente , Hiperpigmentación/diagnóstico , Hiperpigmentación/tratamiento farmacológico , Minociclina/efectos adversos

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BACKGROUND: Knowledge graphs are a common form of knowledge representation in biomedicine and many other fields. We developed an open biomedical knowledge graph-based system termed Reasoning Over Biomedical Objects linked in Knowledge Oriented Pathways (ROBOKOP). ROBOKOP consists of both a front-end user interface and a back-end knowledge graph. The ROBOKOP user interface allows users to posit questions and explore answer subgraphs. Users can also posit questions through direct Cypher query of the underlying knowledge graph, which currently contains roughly 6 million nodes or biomedical entities and 140 million edges or predicates describing the relationship between nodes, drawn from over 30 curated data sources. OBJECTIVE: We aimed to apply ROBOKOP to survey data on workplace exposures and immune-mediated diseases from the Environmental Polymorphisms Registry (EPR) within the National Institute of Environmental Health Sciences. METHODS: We analyzed EPR survey data and identified 45 associations between workplace chemical exposures and immune-mediated diseases, as self-reported by study participants (n= 4574), with 20 associations significant at P<.05 after false discovery rate correction. We then used ROBOKOP to (1) validate the associations by determining whether plausible connections exist within the ROBOKOP knowledge graph and (2) propose biological mechanisms that might explain them and serve as hypotheses for subsequent testing. We highlight the following three exemplar associations: carbon monoxide-multiple sclerosis, ammonia-asthma, and isopropanol-allergic disease. RESULTS: ROBOKOP successfully returned answer sets for three queries that were posed in the context of the driving examples. The answer sets included potential intermediary genes, as well as supporting evidence that might explain the observed associations. CONCLUSIONS: We demonstrate real-world application of ROBOKOP to generate mechanistic hypotheses for associations between workplace chemical exposures and immune-mediated diseases. We expect that ROBOKOP will find broad application across many biomedical fields and other scientific disciplines due to its generalizability, speed to discovery and generation of mechanistic hypotheses, and open nature.

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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.

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Articulación del Codo , Olécranon , Trombocitopenia , Fracturas del Cúbito , Adulto , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/cirugía , Femenino , Humanos , Olécranon/cirugía , Rango del Movimiento Articular , Trombocitopenia/complicaciones , Fracturas del Cúbito/complicaciones , Fracturas del Cúbito/cirugía

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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.

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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.

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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.

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COVID-19 , Bases de Datos Factuales , Humanos , Bases del Conocimiento , Pandemias , SARS-CoV-2