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BACKGROUND: The aim of this retrospective study was to demonstrate that irAEs, specifically gastrointestinal and pulmonary, examined through International Classification of Disease (ICD) data leads to underrepresentation of true irAEs and overrepresentation of false irAEs, thereby concluding that ICD claims data are a poor approach to electronic health record (EHR) data mining for irAEs in immunotherapy clinical research. METHODS: This retrospective analysis was conducted in 1,063 cancer patients who received ICIs between 2011 and 2017. We identified irAEs by manual review of medical records to determine the incidence of each of our endpoints, namely colitis, hepatitis, pneumonitis, other irAE, or no irAE. We then performed a secondary analysis utilizing ICD claims data alone using a broad range of symptom and disease-specific ICD codes representative of irAEs. RESULTS: 16% (n = 174/1,063) of the total study population was initially found to have either pneumonitis 3% (n = 37), colitis 7% (n = 81) or hepatitis 5% (n = 56) on manual review. Of these patients, 46% (n = 80/174) did not have ICD code evidence in the EHR reflecting their irAE. Of the total patients not found to have any irAEs during manual review, 61% (n = 459/748) of patients had ICD codes suggestive of possible irAE, yet were not identified as having an irAE during manual review. DISCUSSION: Examining gastrointestinal and pulmonary irAEs through the International Classification of Disease (ICD) data leads to underrepresentation of true irAEs and overrepresentation of false irAEs.
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Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Classificação Internacional de Doenças/normas , Neoplasias/complicações , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos RetrospectivosRESUMO
PURPOSE: Patients with adolescent idiopathic scoliosis undergoing corrective surgery are at risk for iatrogenic spinal cord injury and subsequent new neurologic deficits (NNDs). Intraoperative neurophysiologic monitoring (IONM) has been used to identify spinal cord injury; however, available data showing that IONM leads to improved clinical outcomes are inconclusive. This exploratory study aimed to examine the incidence of NNDs after idiopathic scoliosis surgery in two pediatric institutions in Canada with a focus on IONM use. METHODS: Charts of pediatric patients (10-18 yr) with adolescent idiopathic scoliosis who underwent scoliosis correction surgery were retrospectively identified from the operating room database. Data regarding incidence and severity (mild [isolated sensory deficit] vs severe [any motor deficit]) of NNDs as well as demographic and clinical characteristics were extracted. RESULTS: Of 547 patients reviewed, 359 (66%) underwent IONM and 186 (34%) underwent wake-up test. Neuromonitoring data were missing in two patients. Total incidence of NNDs was 4.9% (95% confidence interval [CI], 3.1 to 6.8). Compared with the wake-up test, patients undergoing IONM were less likely to develop NNDs (unadjusted odds ratio, 0.39; 95% CI, 0.18 to 0.86; P = 0.02). Nevertheless, subgroup analysis did not reveal a statistical difference in severity of those deficits (mild vs severe) with IONM vs wake-up test. Combined anterior and posterior approach was also significantly associated with increased risk of such deficits. CONCLUSION: This exploratory study revealed that IONM was associated with a reduced overall incidence of NNDs in idiopathic scoliosis correction; however, its impact on the severity of those deficits is questionable. As we were unable to adjust for confounding variables, further research is needed to determine the impact of IONM on NNDs.
RéSUMé: OBJECTIF: Les patients adolescents atteints de scoliose idiopathique subissant une chirurgie corrective sont à risque de lésions médullaires iatrogéniques et de nouveaux déficits neurologiques (NDN) subséquents. Le monitorage neurophysiologique peropératoire (MNP) a été employé pour identifier les lésions médullaires; cependant, les données disponibles montrant que le MNP entraîne de meilleurs pronostics cliniques ne sont pas concluantes. Cette étude exploratoire visait à examiner l'incidence des NDN après une chirurgie de scoliose idiopathique dans deux établissements pédiatriques au Canada en se concentrant sur l'utilisation du MNP. MéTHODE: Les dossiers des patients pédiatriques (10-18 ans) atteints de scoliose idiopathique ayant subi une chirurgie de correction de scoliose ont été rétrospectivement identifiés dans la base de données de salle d'opération. Les données concernant l'incidence et la gravité (légers [déficit sensoriel isolé] vs graves [tout déficit moteur]) des NDN ainsi que les caractéristiques démographiques et cliniques ont été extraites. RéSULTATS: Parmi les 547 patients passés en revue, 359 (66 %) ont eu un MNP et 186 (34 %) ont eu un test d'éveil ('wake-up test'). Les données de monitorage neurologique manquaient pour deux patients. L'incidence totale des NDN était de 4,9 % (intervalle de confiance [IC] de 95 %, 3,1 à 6,8). Par rapport au test d'éveil, les patients subissant un MNP étaient moins susceptibles de présenter des NDN (rapport de cotes non ajusté, 0,39; IC 95 %, 0,18 à 0,86; P = 0,02). Néanmoins, l'analyse des sous-groupes n'a pas révélé de différence statistique dans la gravité de ces déficits (légers vs graves) en comparant un MNP à un test d'éveil. Une association significative a également été relevée entre une approche combinée chirurgicale antérieure et postérieure et un risque accru de tels déficits. CONCLUSION: Cette étude exploratoire a indiqué que le MNP était associé à une incidence globale réduite de NDN lors d'une chirurgie de correction de scoliose idiopathique; toutefois, son impact sur la gravité de ces déficits est discutable. Comme nous n'avons pas été en mesure d'ajuster les données aux variables confondantes, d'autres recherches sont nécessaires pour déterminer l'impact du MNP sur les NDN.
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Monitorização Neurofisiológica Intraoperatória , Escoliose , Adolescente , Canadá/epidemiologia , Criança , Potenciais Somatossensoriais Evocados , Humanos , Estudos Retrospectivos , Escoliose/cirurgiaRESUMO
Page kidney is a pathologic and rare occurrence caused by a compression of renal parenchyma leading to hypertension. When infiltrated or engulfed by extrinsic matter, the subcapsular region surrounding the renal tissue may cause blanket compression, leading to the activation of the renin-angiotensin-aldosterone system secondary to renal hypoperfusion. While most cases of Page kidney are secondary to blunt trauma to the costovertebral angle, herein we present a case of Page kidney due to renal parenchymal core needle biopsy. The rarity of our case is not due to the cause of such an incidence but because our case resulted in a hypertensive emergency treated with dual intravenous infusions.
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INTRODUCTION: The diagnosis of erectile dysfunction (ED) often involves a combination of patient history, questionnaire responses, and laboratory results. Penile duplex ultrasound (PDU) with intracavernous injection of papaverine was introduced as a noninvasive tool to aid in the evaluation of penile circulation. Although PDU is widely used in the initial workup of ED, the true value and effect of PDU on management is still unclear. OBJECTIVE: The objective of this systematic review was to determine if PDU affects ED management. METHODS: A systematic literature review was conducted using PUBMED-Medline databases in June 2020, which included literature from 1991 through 2019. The search strategy used MeSH terms "penile", "duplex ultrasound", or "duplex ultrasonography". The database process yielded a total of 389 terms. Systematic review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. RESULTS: 6 studies were included in the final analysis and included a total of 386 patients. These articles each discussed the clinical utility of PDU using venous and arterial parameters and correlated treatment response to sexual functioning questionnaires. The majority of the studies demonstrated PDU was unnecessary for diagnosis and ultimately did not affect treatment decision-making. CONCLUSION: PDU generally does not change management in men with established organic ED but may prove useful in special populations such as in younger patients or patients with anatomical abnormalities. Limitations include the small number of focused studies on the topic and paucity of randomized trials investigating PDU and clinician decision-making. Further investigations and studies are needed to determine if PDU modifies ED provider's management decision-making. Nashed A, Lokeshwar SD, Frech F, et al. The Efficacy of Penile Duplex Ultrasound in Erectile Dysfunction Management Decision-Making: A Systematic Review. Sex Med Rev 2021;9:472-477.
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Disfunção Erétil , Disfunção Erétil/diagnóstico por imagem , Disfunção Erétil/terapia , Humanos , Masculino , Papaverina , Pênis/diagnóstico por imagem , Inquéritos e QuestionáriosRESUMO
Spheroids are increasingly being employed to answer a wide range of clinical and biomedical inquiries ranging from pharmacology to disease pathophysiology, with the ultimate goal of using spheroids for tissue engineering and regeneration. When compared to traditional two-dimensional cell culture, spheroids have the advantage of better replicating the 3D extracellular microenvironment and its associated growth factors and signaling cascades. As knowledge about the preparation and maintenance of spheroids has improved, there has been a plethora of translational experiments investigating in vivo implantation of spheroids into various animal models studying tissue regeneration. We review methods for spheroid delivery and how they have been utilized in tissue engineering experiments. We break down efforts in this field by organ systems, discussing applications of spheroids to various animal models of disease processes and their potential clinical implications. These breakthroughs have been made possible by advancements in spheroid formation, in vivo delivery and assessment. There is unexplored potential and room for further research and development in spheroid-based tissue engineering approaches. Regenerative medicine and other clinical applications ensure this exciting area of research remains relevant for patient care.
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Terapia Baseada em Transplante de Células e Tecidos , Medicina Regenerativa , Esferoides Celulares , Engenharia Tecidual , Animais , HumanosRESUMO
The human gut is heavily colonized by a community of microbiota, primarily bacteria, that exists in a symbiotic relationship with the host and plays a critical role in maintaining host homeostasis. The consumption of a high-fat (HF) diet has been shown to induce gut dysbiosis and reduce intestinal integrity. Recent studies have revealed that dysbiosis contributes to the progression of cardiovascular diseases (CVDs) by promoting two major CVD risk factors-atherosclerosis and hypertension. Imbalances in host-microbial interaction impair homeostatic mechanisms that regulate health and can activate multiple pathways leading to CVD risk factor progression. Dysbiosis has been implicated in the development of atherosclerosis through metabolism-independent and metabolite-dependent pathways. This review will illustrate how these pathways contribute to the various stages of atherosclerotic plaque progression. In addition, dysbiosis can promote hypertension through vascular fibrosis and an alteration of vascular tone. As CVD is the number one cause of death globally, investigating the gut microbiota as a locus of intervention presents a novel and clinically relevant avenue for future research, with vast therapeutic potential.
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Doenças Cardiovasculares , Disbiose/microbiologia , Microbioma Gastrointestinal , Aterosclerose/etiologia , Aterosclerose/terapia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Humanos , Hipertensão/etiologia , Hipertensão/terapia , Microbiota/fisiologia , ProbióticosRESUMO
This protocol describes 3D bioprinting of cardiac tissue without the use of biomaterials, using only cells. Cardiomyocytes, endothelial cells and fibroblasts are first isolated, counted and mixed at desired cell ratios. They are co-cultured in individual wells in ultra-low attachment 96-well plates. Within 3 days, beating spheroids form. These spheroids are then picked up by a nozzle using vacuum suction and assembled on a needle array using a 3D bioprinter. The spheroids are then allowed to fuse on the needle array. Three days after 3D bioprinting, the spheroids are removed as an intact patch, which is already spontaneously beating. 3D bioprinted cardiac patches exhibit mechanical integration of component spheroids and are highly promising in cardiac tissue regeneration and as 3D models of heart disease.
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Bioimpressão/métodos , Miócitos Cardíacos/citologia , Esferoides Celulares/citologia , Engenharia Tecidual/métodos , Humanos , Miócitos Cardíacos/metabolismo , Esferoides Celulares/metabolismoRESUMO
We have developed a novel method to deliver stem cells using 3D bioprinted cardiac patches, free of biomaterials. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), fibroblasts (FB) and endothelial cells (EC) were aggregated to create mixed cell spheroids. Cardiac patches were created from spheroids (CM:FB:EC = 70:15:15, 70:0:30, 45:40:15) using a 3D bioprinter. Cardiac patches were analyzed with light and video microscopy, immunohistochemistry, immunofluorescence, cell viability assays and optical electrical mapping. Cardiac tissue patches of all cell ratios beat spontaneously after 3D bioprinting. Patches exhibited ventricular-like action potential waveforms and uniform electrical conduction throughout the patch. Conduction velocities were higher and action potential durations were significantly longer in patches containing a lower percentage of FBs. Immunohistochemistry revealed staining for CM, FB and EC markers, with rudimentary CD31+ blood vessel formation. Immunofluorescence revealed the presence of Cx43, the main cardiac gap junction protein, localized to cell-cell borders. In vivo implantation suggests vascularization of 3D bioprinted cardiac patches with engraftment into native rat myocardium. This constitutes a significant step towards a new generation of stem cell-based treatment for heart failure.
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Materiais Biocompatíveis , Bioimpressão , Células-Tronco Pluripotentes Induzidas , Miócitos Cardíacos , Impressão Tridimensional , Engenharia Tecidual , Alicerces Teciduais , Animais , Materiais Biocompatíveis/química , Diferenciação Celular , Células Cultivadas , Fenômenos Eletrofisiológicos , Células Endoteliais , Fibroblastos/citologia , Fibroblastos/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Miocárdio/citologia , Miocárdio/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/fisiologia , Ratos , Esferoides Celulares , Transplante de TecidosRESUMO
BACKGROUND: Currently, there is a lack of knowledge regarding patient perceptions surrounding physician reimbursements, appropriate wait times, and out-of-pocket payment options for anterior cruciate ligament reconstruction (ACLR). Our objective was to determine the current state of these perceptions in an Ontario setting. METHODS: A survey was developed and pretested to address patient perceptions about physician reimbursements, appropriate wait times, and out-of-pocket payment options for ACLR using a focus group of experts and by reviewing prior surveys. The survey was administered to patients in a waiting room setting. RESULTS: Two hundred and fifty completed surveys were obtained (79.9% response rate). Participants responded that an appropriate physician reimbursement for ACLR was $1000.00 and that the Ontario Health Insurance Plan (OHIP) reimbursed physicians $700.00 for ACLR. Seventy-four percent of participants responded that the OHIP reimbursement of $615.20 for the procedure was either lower or much lower than what they considered to be an appropriate reimbursement for ACLR. Over 90% of participants responded that an ACLR should occur within 90 days of injury. Thirty-five percent of participants were willing to pay $750.00 out-of-pocket to have an ACLR done sooner, while 16.4% of participants were willing to pay $2500.00 out-of-pocket to travel outside of Canada for expedited surgery. CONCLUSION: This survey study demonstrates that patients' estimates of both appropriate and actual physician reimbursements were greater than the current reimbursement for ACLR. Further, the majority of individuals report that the surgical fee for ACLR is lower than what they consider to be an appropriate amount of compensation for the procedure. Additionally, nearly all respondents believe that a ruptured ACL should be reconstructed within 90 days of injury. Consequently, a number of patients are willing to pay out-of-pocket for expedited surgery either in Canada or abroad. However, patients' preferences for shorter wait times must be balanced with the known risk of arthrofibrosis associated with early ACLR.