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1.
Hum Mol Genet ; 33(8): 698-708, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38268317

RESUMO

Identifying the aberrant expression of DUX4 in skeletal muscle as the cause of facioscapulohumeral dystrophy (FSHD) has led to rational therapeutic development and clinical trials. Several studies support the use of MRI characteristics and the expression of DUX4-regulated genes in muscle biopsies as biomarkers of FSHD disease activity and progression. We performed lower-extremity MRI and muscle biopsies in the mid-portion of the tibialis anterior (TA) muscles bilaterally in FSHD subjects and validated our prior reports of the strong association between MRI characteristics and expression of genes regulated by DUX4 and other gene categories associated with FSHD disease activity. We further show that measurements of normalized fat content in the entire TA muscle strongly predict molecular signatures in the mid-portion of the TA, indicating that regional biopsies can accurately measure progression in the whole muscle and providing a strong basis for inclusion of MRI and molecular biomarkers in clinical trial design. An unanticipated finding was the strong correlations of molecular signatures in the bilateral comparisons, including markers of B-cells and other immune cell populations, suggesting that a systemic immune cell infiltration of skeletal muscle might have a role in disease progression.


Assuntos
Distrofia Muscular Facioescapuloumeral , Humanos , Distrofia Muscular Facioescapuloumeral/diagnóstico por imagem , Distrofia Muscular Facioescapuloumeral/genética , Distrofia Muscular Facioescapuloumeral/metabolismo , Proteínas de Homeodomínio/genética , Ensaios Clínicos como Assunto , Músculo Esquelético/metabolismo , Imageamento por Ressonância Magnética , Biomarcadores/metabolismo , Progressão da Doença
2.
PLoS Biol ; 21(9): e3002317, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37747887

RESUMO

Translational control is critical for cell fate transitions during development, lineage specification, and tumorigenesis. Here, we show that the transcription factor double homeobox protein 4 (DUX4), and its previously characterized transcriptional program, broadly regulates translation to change the cellular proteome. DUX4 is a key regulator of zygotic genome activation in human embryos, whereas misexpression of DUX4 causes facioscapulohumeral muscular dystrophy (FSHD) and is associated with MHC-I suppression and immune evasion in cancer. We report that translation initiation and elongation factors are disrupted downstream of DUX4 expression in human myoblasts. Genome-wide translation profiling identified mRNAs susceptible to DUX4-induced translation inhibition, including those encoding antigen presentation factors and muscle lineage proteins, while DUX4-induced mRNAs were robustly translated. Endogenous expression of DUX4 in human FSHD myotubes and cancer cell lines also correlated with reduced protein synthesis and MHC-I presentation. Our findings reveal that DUX4 orchestrates cell state conversion by suppressing the cellular proteome while maintaining translation of DUX4-induced mRNAs to promote an early developmental program.


Assuntos
Proteínas de Homeodomínio , Distrofia Muscular Facioescapuloumeral , Fatores de Transcrição , Humanos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Músculo Esquelético/metabolismo , Distrofia Muscular Facioescapuloumeral/genética , Distrofia Muscular Facioescapuloumeral/metabolismo , Proteoma/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
3.
Hum Mol Genet ; 32(11): 1864-1874, 2023 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-36728804

RESUMO

Human DUX4 and its mouse ortholog Dux are normally expressed in the early embryo-the 4-cell or 2-cell cleavage stage embryo, respectively-and activate a portion of the first wave of zygotic gene expression. DUX4 is epigenetically suppressed in nearly all somatic tissue, whereas facioscapulohumeral dystrophy (FSHD)-causing mutations result in its aberrant expression in skeletal muscle, transcriptional activation of the early embryonic program and subsequent muscle pathology. Although DUX4 and Dux both activate an early totipotent transcriptional program, divergence of their DNA binding domains limits the use of DUX4 expressed in mice as a preclinical model for FSHD. In this study, we identify the porcine DUXC messenger ribonucleic acid expressed in early development and show that both pig DUXC and human DUX4 robustly activate a highly similar early embryonic program in pig muscle cells. These results support further investigation of pig preclinical models for FSHD.


Assuntos
Distrofia Muscular Facioescapuloumeral , Humanos , Animais , Camundongos , Suínos , Distrofia Muscular Facioescapuloumeral/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Células Musculares/metabolismo , Músculo Esquelético/metabolismo
4.
Prev Chronic Dis ; 21: E03, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38207177

RESUMO

HIV has evolved from a serious infectious disease to a manageable chronic disease. Tobacco use has a devastating effect on the health of people living with HIV/AIDS (PLWH). The Michigan Tobacco Use Reduction Program for PLWH was established in 2015 to learn about tobacco use among PLWH, gather information on entities that provide health care services to PLWH, and improve tobacco treatment services for this population. The program offers evidence-based treatment interventions to all PLWH who are tobacco users, eligible for the Ryan White HIV/AIDS Program, and served by AIDS service organizations in Michigan. This evaluation had 3 primary outcomes: 1) rates of smoking and tobacco use among program clients, 2) the percentage of clients who made a quit attempt in the previous 12 months, and 3) the types of tobacco cessation methods used by clients. All data were self-reported in 3 surveys, one each in 2015, 2017, and 2021. The rate of cigarette smoking overall among clients decreased significantly from 49.5% in 2015 to 41.5% in 2017. The percentage of clients who made a quit attempt increased from 37.0% in 2015 to 41.9% in 2017; in 2021, this rate was 54.4%. By age, in all 3 survey years, the highest rate of tobacco use was among clients aged 35 to 44 years (range, 48.4%-57.4%). Smoking rates declined significantly from 2015 to 2017 among African American (50.5% to 42.8%) and White clients (49.8% to 39.9%). The most frequently used method of tobacco cessation was medications prescribed by a physician (range, 20%-30%). State tobacco control programs are encouraged to collaborate with their state HIV/AIDS bureaus to create similar programs to treat tobacco use among PLWH.


Assuntos
Síndrome da Imunodeficiência Adquirida , Fumar Cigarros , Infecções por HIV , Abandono do Hábito de Fumar , Humanos , Pré-Escolar , Síndrome da Imunodeficiência Adquirida/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Michigan/epidemiologia , Abandono do Hábito de Fumar/métodos , Prevalência , Produtos do Tabaco
5.
Law Hum Behav ; 47(1): 36-52, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36931848

RESUMO

OBJECTIVE: Given the greater contact that Black youth have with the legal system compared with White youth, it is important to consider the differential ways that police use of force against these youth is perceived. Black youth may be at greater risk than White youth for animalistic (being seen as animal-like) and mechanistic (being seen as object-like) dehumanization, which, along with a tendency for Black youth to be perceived as older (adultification), may impact observers' perceptions of police use of force toward Black youth. This study examined whether dehumanization and adultification were associated with the perceptions of force used and harm caused by police. HYPOTHESES: We made five hypotheses. First, participants would dehumanize Black individuals more than White individuals, more mechanistically dehumanize Black women than Black men, and more animalistically dehumanize Black men than Black women. Second, dehumanization would be positively associated with adultification. Third, force would be rated as less appropriate and more excessive for White than for Black targets, particularly for males. Fourth, dehumanization, particularly animalistic dehumanization, would be associated with higher participant ratings of force justification and lower participant ratings of force severity and excessiveness. Fifth, participants would perceive girls as more harmed than boys and White individuals as more harmed than Black individuals. METHOD: After completing an implicit dehumanization measure, participants viewed an image (varied on age and gender) of a juvenile, estimated the juvenile's age, and read a vignette in which the juvenile had an altercation with police. Participants rated the amount, severity, and justification of the force used by the officer as well as the physical and emotional harm caused to the juvenile. RESULTS: We found that Black targets were dehumanized more than White targets. Adultification, unrelated to implicit dehumanization, predicted perceiving police use of force against juveniles as more justified and less severe. Black girls were most likely to experience adultification; participants generally perceived them as less victimized than Black boys and White girls. CONCLUSIONS: Adultification is associated with fewer protections for youth. Those with particular intersectional identities, such as Black girls, may be uniquely vulnerable to harm caused by police victimization. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
População Negra , Vítimas de Crime , Desumanização , Polícia , Feminino , Humanos , Masculino , Emoções
6.
Ann Surg ; 276(5): e450-e458, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33214481

RESUMO

OBJECTIVE: We examined the impact of upfront small bowel resection (USBR) for metastatic small bowel neuroendocrine (SB-NET) compared to nonoperative management (NOM) on long-term healthcare utilization and survival outcomes. SUMMARY OF BACKGROUND DATA: The role of early resection of the primary tumor in metastatic SB-NET remains controversial. Conflicting data exist regarding its clinical and survival benefits. METHODS: This is a population-based retrospective matched comparative cohort study of adults diagnosed with synchronous metastatic SB-NET between 2001 and 2017 in Ontario. USBR was defined as resection within 6 months of diagnosis. Primary outcomes were subsequent unplanned acute care admissions and small bowel-related surgery. Secondary outcome was overall survival. USBR and NOM patients were matched 2:1 using a propensity-score. We used time-to-event analyses with cumulative incidencefunctions and univariate Andersen-Gill regression for primary outcomes. E value methods assessed the potential for residual confounding. RESULTS: Of 1000 patients identified, 785 had USBR. The matched cohort included 348 patients with USBR and 174 with NOM. Patients with USBR had lower 3-year risk of subsequent admissions (72.6% vs 86.4%, P < 0.001) than those with NOM, with hazard ratio 0.72 (95% confidence interval 0.570.91). USBR was associated with lower risk of subsequent small bowel-related surgery (15.4% vs 40.3%, P < 0.001), with hazard ratio 0.44 (95% confidence interval 0.29-0.67). E -values indicated it was unlikely that the observed risk estimates could be explained by an unmeasured confounder. Sensitivity analysis excluding emergent resections to define USBR did not alter the results. CONCLUSIONS: USBR for SB-NETs in the presence of metastatic disease was associated with better patient-oriented outcomes of decreased subsequent admissions and interventions, compared to NOM. USBR should be considered for metastatic SB-NETs.


Assuntos
Neoplasias Intestinais , Tumores Neuroendócrinos , Adulto , Estudos de Coortes , Humanos , Neoplasias Intestinais/cirurgia , Neoplasias Pancreáticas , Estudos Retrospectivos , Neoplasias Gástricas
7.
Ann Surg ; 276(6): e851-e860, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33914463

RESUMO

OBJECTIVE: To evaluate healthcare dependency following hepatopancreato-biliary cancer surgery in older adults (OA). SUMMARY BACKGROUND DATA: Functional outcomes are central to decisionmaking by OA, but long-term risks of dependency have not been described beyond 1 year in this population. METHODS: All patients over age 70 undergoing hepatectomy or pancreatec-tomy for cancer between 2007 and 2017 in Ontario were analyzed. Outcomes were 1) receipt of homecare and 2) time at home. Homecare was analyzed with cumulative incidence functions, and time at home with Kaplan-Meier and Cox multivariate models. RESULTS: A total of 902 and 1283 patients underwent hepatectomy and pancreatectomy, respectively. Homecare use was highest (72.3%) in postoperative month-1, decreasing to stabilize between year-1 (25.5%) and year-5 (18.3%). Repeated receipt of homecare was associated with female sex (HR 1.18, 95% CI 1.05-1.32), receipt of adjuvant therapy (HR 1.56, 1.37-1.78), and more recent year of surgery (HR 3.80, 3.05-4.72). The ratio of home nursing care versus personal support services reversed from 68%/26% in year-1, to 29/64% in year-5. High time at home (>350 days) at 1 and 5 years were 40.6% (95% CI 38.5%-42.6%) and 28.1% (25.9%-30.3%), respectively. The ratio of institution-days in acute care versus nursing homes went from 77%/14% in year-1 to 23%/70% in year-5. Low time at home was associated with duodenal (HR 1.45, 1.15-1.70) and pancreas cancer (HR 1.20, 1.02-1.42), and with rural residence (HR 1.24, 1.04-1.48). High time at home was associated with more recent year of surgery (HR 0.84, 0.76-0.93) and perioperative cancer therapy (HR 0.88, 0.78-0.99). Increasing age was neither associated with homecare receipt nor time at home. CONCLUSIONS: Following hepatopancreatobiliary cancer surgery, there is a high rate of long-term healthcare dependency for OA. There is an immediate high need for homecare that reaches a new baseline after 6 months, and the majority of OA will have at least 1 year with low time at home, most commonly the first year. These findings can aid in preoperative preparation and transitional care planning.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar , Serviços de Assistência Domiciliar , Neoplasias , Humanos , Feminino , Idoso , Casas de Saúde , Pancreatectomia
8.
Sensors (Basel) ; 22(24)2022 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-36560355

RESUMO

Exoskeletons and exosuits (collectively termed EXOs) have the potential to reduce the risk of work-related musculoskeletal disorders (WMSDs) by protecting workers from exertion and muscle fatigue due to physically demanding, repetitive, and prolonged work in construction workplaces. However, the use of EXOs in construction is in its infancy, and much of the knowledge required to drive the acceptance, adoption, and application of this technology is still lacking. The objective of this research is to identify the facilitators, barriers, and corresponding solutions to foster the adoption of EXOs in construction workplaces through a sequential, multistage Delphi approach. Eighteen experts from academia, industry, and government gathered in a workshop to provide insights and exchange opinions regarding facilitators, barriers, and potential solutions from a holistic perspective with respect to business, technology, organization, policy/regulation, ergonomics/safety, and end users (construction-trade professionals). Consensus was reached regarding all these perspectives, including top barriers and potential solution strategies. The outcomes of this study will help the community gain a comprehensive understanding of the potential for EXO use in the construction industry, which may enable the development of a viable roadmap for the evolution of EXO technology and the future of EXO-enabled workers and work in construction workplaces.


Assuntos
Indústria da Construção , Exoesqueleto Energizado , Doenças Profissionais , Humanos , Doenças Profissionais/prevenção & controle , Ergonomia/métodos , Local de Trabalho
9.
Hum Mol Genet ; 28(23): 3997-4011, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31630170

RESUMO

The DUX4 transcription factor is normally expressed in the cleavage-stage embryo and regulates genes involved in embryonic genome activation. Misexpression of DUX4 in skeletal muscle, however, is toxic and causes facioscapulohumeral muscular dystrophy (FSHD). We recently showed DUX4-induced toxicity is due, in part, to the activation of the double-stranded RNA (dsRNA) response pathway and the accumulation of intranuclear dsRNA foci. Here, we determined the composition of DUX4-induced dsRNAs. We found that a subset of DUX4-induced dsRNAs originate from inverted Alu repeats embedded within the introns of DUX4-induced transcripts and from DUX4-induced dsRNA-forming intergenic transcripts enriched for endogenous retroviruses, Alu and LINE-1 elements. However, these repeat classes were also represented in dsRNAs from cells not expressing DUX4. In contrast, pericentric human satellite II (HSATII) repeats formed a class of dsRNA specific to the DUX4 expressing cells. Further investigation revealed that DUX4 can initiate the bidirectional transcription of normally heterochromatin-silenced HSATII repeats. DUX4-induced HSATII RNAs co-localized with DUX4-induced nuclear dsRNA foci and with intranuclear aggregation of EIF4A3 and ADAR1. Finally, gapmer-mediated knockdown of HSATII transcripts depleted DUX4-induced intranuclear ribonucleoprotein aggregates and decreased DUX4-induced cell death, suggesting that HSATII-formed dsRNAs contribute to DUX4 toxicity.


Assuntos
DNA Satélite/genética , Proteínas de Homeodomínio/metabolismo , Distrofia Muscular Facioescapuloumeral/genética , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismo , Linhagem Celular , DNA Satélite/metabolismo , Regulação da Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Íntrons , Modelos Biológicos , Músculo Esquelético/metabolismo , Distrofia Muscular Facioescapuloumeral/metabolismo , Mioblastos/metabolismo , RNA de Cadeia Dupla/metabolismo , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição/genética
10.
Can J Surg ; 64(4): E428-E434, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34323064

RESUMO

Background: Educational videos have become valuable resources and can address some of the pitfalls of traditional learning. To ensure clerkship students have adequate exposure to curriculum objectives, a series of objective-aligned self-directed learning video podcasts covering core surgical concepts were developed by medical students and surgical residents. The objective of the study was to evaluate the efficacy of the video podcasts in the surgery clerkship rotation. Methods: Nineteen video podcasts were created, housed at www.surgicaleducationportal.com, and distributed to third-year medical students completing their surgical clerkship. A 10-question multiple-choice quiz was administered before and after students viewed each video, and they were also asked to complete a satisfaction survey. Results: A total of 302 paired pretests and posttests were completed. There was a mean increase of 2.7 points in posttest scores compared with pretest scores (p < 0.001). On a Likert scale from 1 to 5, with 5 being excellent, students rated the usefulness of the videos as 4.3, the quality of the content as 4.3 and the quality of the video as 4.2. Ninety-eight percent of students would recommend these videos to their classmates. Conclusion: Video podcasts are an effective modality for engaging medical students and may improve standardization of learning during their surgical clerkship.


Contexte: Les vidéos de formation sont devenues d'inestimables ressources et elles peuvent combler certaines des lacunes de l'enseignement traditionnel. Pour que les résidents bénéficient d'une exposition adéquate aux objectifs curriculaires, une série de balados vidéo d'autoapprentissage centrés sur des objectifs reliés aux principaux concepts de chirurgie a été réalisée par des étudiants en médecine et des résidents en chirurgie. L'objectif de l'étude était d'évaluer l'efficacité des balados pour les stages de chirurgie. Méthodes: Dix-neuf balados vidéo ont été réalisés (accessibles en anglais au www.surgicaleducationportal.com) et distribués à des étudiants de troisième année de médecine qui effectuent leur stage de chirurgie. Un questionnaire en 10 points à choix multiples leur a été administré avant et après le visionnement de chaque vidéo; ils ont ensuite été invités à répondre à un questionnaire d'évaluation. Résultats: En tout 302 pré- et post-tests appariés ont été effectués. On a observé une augmentation de 2,7 points aux scores post-test, comparativement aux scores pré-test (p < 0,001). Sur une échelle de Likert allant de 1 à 5, 5 correspondant à excellent, les étudiants ont accordé un score de 4,3 pour l'utilité des balados vidéo et de 4,2 pour leur qualité. Quatre-vingt-dix-huit pour cent des étudiants recommanderaient ces balados vidéo à leurs camarades. Conclusion: Les balados vidéo sont une modalité efficace pour mobiliser les étudiants en médecine et pourraient faciliter l'uniformisation de l'apprentissage lors des stages de chirurgie.


Assuntos
Estágio Clínico , Educação de Graduação em Medicina , Estudantes de Medicina , Webcasts como Assunto , Atitude do Pessoal de Saúde , Avaliação Educacional , Cirurgia Geral/educação , Humanos , Ontário , Ortopedia/educação , Urologia/educação
11.
HPB (Oxford) ; 21(6): 757-764, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30501988

RESUMO

BACKGROUND: Perioperative red blood cell (RBC) transfusion is associated with poor outcomes in liver surgery. Hypovolemic phlebotomy (HP) is a novel intervention hypothesized to decrease transfusion requirements. The objective of this study was to examine this hypothesis. METHODS: Consecutive patients who underwent liver resection at one institution (2010-2016) were included. Factors found to be predictive of transfusion on univariate analysis and those previously published were modeled using multivariate logistic regression. RESULTS: A total of 361 patients underwent liver resection (50% major). HP was performed in 45 patients. Phlebotomized patients had a greater proportion of primary malignancy (31% vs 18%) and major resection (84% vs 45%). Blood loss was significantly lower with phlebotomy in major resections (400 vs 700 mL). Nadir central venous pressure was significantly lower with HP (2.5 vs 5 cm H2O). On multivariate logistic regression, HP (OR 0.20, 95% CI 0.068-0.57, p = 0.0029), major liver resection (OR 2.91, 95% CI 1.64-5.18, p = 0.0003), preoperative hemoglobin < 125 g/L (OR 6.02, 95% CI 3.44-10.56, p < 0.0001), and underlying liver disease (OR 2.24, 95% CI 1.27-3.95, p = 0.0051) were significantly associated with perioperative RBC transfusion. CONCLUSION: Hypovolemic phlebotomy appears to be strongly associated with a reduction in RBC transfusion requirements in liver resection, independent of other known risk factors.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Eritrócitos/estatística & dados numéricos , Hepatectomia/efeitos adversos , Hipovolemia/etiologia , Flebotomia/métodos , Pressão Venosa Central/fisiologia , Transfusão de Eritrócitos/efeitos adversos , Feminino , Seguimentos , Humanos , Hipovolemia/fisiopatologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
12.
Ann Surg ; 267(4): 766-774, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28288056

RESUMO

OBJECTIVE: Create practice guidelines for the appropriate use of red blood cell transfusions in hepatectomy. BACKGROUND: Hepatectomy is associated with a high prevalence of transfusions. A transfusion can be life-saving, but can be associated with important adverse effects. Given the prevalence, the potential for benefit and harm, and the difficulty in conducting clinical trials, transfusion in hepatectomy is well-suited for a study of appropriateness. METHODS: Using the RAND/UCLA appropriateness method, an international, multidisciplinary expert panel in hepatobiliary surgery, anesthesia, transfusion medicine, and critical care rated a series of 468 perioperative scenarios for transfusion appropriateness. Scenarios were rated individually, and again during an inperson group moderated session. Median scores and level of agreement were calculated to classify each scenario as appropriate, inappropriate, or uncertain. RESULTS: Approximately, 47.4% of scenarios were rated as appropriate for transfusion, 28.2% were inappropriate, and 24.4% were uncertain. The key recommendations for intraoperative transfusion were (i) it is never inappropriate to transfuse for significant bleeding or ST segment changes; (ii) it is never inappropriate to transfuse for an intraoperative hemoglobin ≤75 g/L; and (iii) in the absence of significant bleeding or ST changes, transfusion for hemoglobin of ≥95 g/L is inappropriate, and transfusion for hemoglobin of ≥85 g/L requires strong justification. The key recommendations for postoperative transfusions were: (i) in a stable, asymptomatic patient, an appropriate transfusion trigger is 70 g/L (without coronary artery disease) or 80 g/L (with coronary artery disease) and (ii) it is appropriate to transfuse any patient for a hemoglobin of ≤75 g/L either immediately post-operative, or with a significant decrease from the previous day (>15 g/L). CONCLUSIONS: Based on best available evidence and expert opinion, criteria for appropriate perioperative red blood cell transfusions in hepatectomy were determined.


Assuntos
Perda Sanguínea Cirúrgica , Transfusão de Eritrócitos , Hepatectomia/efeitos adversos , Guias de Prática Clínica como Assunto , Fatores Etários , Canadá , Tomada de Decisão Clínica , Doença da Artéria Coronariana , Medicina Baseada em Evidências , Prova Pericial , Frequência Cardíaca , Hemodinâmica , Hemoglobinometria , Humanos , Cooperação Internacional , Complicações Pós-Operatórias/terapia , Estados Unidos
13.
Transfusion ; 58(3): 781-787, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29322515

RESUMO

BACKGROUND: Development of intraoperative techniques and blood management strategies in liver resection, and the multidisciplinary nature of perioperative transfusion decision making, creates an opportunity for practice variation. The aim of this study was to describe the current practices in perioperative blood management and explore differences between surgeons and anesthesiologists. STUDY DESIGN AND METHODS: A Web-based survey was developed, piloted, and circulated to Canadian liver surgeons and anesthesiologists. The survey focused on management of preoperative anemia, blood conservation strategies, estimation of blood loss, and transfusion decision making in a multidisciplinary setting. RESULTS: A total of 198 physicians received the survey, with 117 responding (59%). Most responding surgeons (67%) perform more than 20 liver resections per year, while most responding anesthesiologists (90%) take part in fewer than 20. Anesthesiologists most commonly stated that preoperative anemia is managed by someone else (38%), while surgeons most commonly reported "no specific treatment" (45%). The most common intraoperative blood conservation technique used is administration of antifibrinolytics (63% used them at least occasionally). The most important factor for anesthesiologists when deciding on an intraoperative transfusion was hemoglobin value (47%); for surgeons, it was patient hemodynamics (33%). Compared to when they started their career, 60% of respondents felt that they were less likely to transfuse a patient now. CONCLUSION: The results of our survey provide insights into current transfusion practice and decision making in liver resection, including a comparison between anesthesiologist and surgeon transfusion behavior. Management of preoperative anemia, increased use of intraoperative blood conservation techniques, and improved communication between providers were identified as targets for quality improvement.


Assuntos
Anestesiologistas , Transfusão de Sangue , Tomada de Decisões , Hepatectomia , Recuperação de Sangue Operatório/métodos , Assistência Perioperatória/métodos , Cirurgiões , Inquéritos e Questionários , Anemia/sangue , Anemia/cirurgia , Canadá , Feminino , Humanos , Masculino
14.
World J Surg ; 42(9): 2938-2950, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29464346

RESUMO

BACKGROUND: There is significant interest and controversy surrounding the effect of restrictive fluid management on outcomes in major gastrointestinal surgery. This has been most studied in colorectal surgery, although the literature relating to pancreaticoduodenectomy (PD) patients is growing. The aim of this paper was to generate a comprehensive review of the available evidence for restrictive perioperative fluid management strategies and outcomes in PD. METHODS: MEDLINE/PubMed, Embase, and the Cochrane Library were searched from inception to April 2017. A review protocol was utilized and registered with PROSPERO. Primary citations that evaluated perioperative fluid management in PD, including those as part of a clinical pathway, were considered. The primary outcome was postoperative pancreatic fistula (POPF). Secondary outcomes included delayed gastric emptying (DGE), complication rate, length of stay (LOS), mortality, and readmission. RESULTS: A total of six studies involving 846 patients were included (2009-2015), of which four were RCTs. Pooled analysis of RCTs and high-quality observational studies found no effect of restrictive intraoperative fluid management on POPF, DGE, complication rate, LOS, mortality, and readmission. Only one study assessed postoperative fluid management exclusively and found prolonged LOS in patients in the restricted fluid group. CONCLUSION: Based on results of RCTs and high-quality observational studies, intraoperative fluid restriction in PD has not been shown to significantly affect postoperative outcomes. There are too few studies assessing postoperative fluid management to draw conclusions at this time.


Assuntos
Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Anastomose Cirúrgica/efeitos adversos , Esvaziamento Gástrico , Gastroparesia/etiologia , Humanos , Tempo de Internação , Readmissão do Paciente , Complicações Pós-Operatórias/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
Can J Surg ; 61(6): 424-429, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30468378

RESUMO

Background: The use of outpatient health care services by homeless people is low compared to their high level of need; however, it is unclear whether this applies to surgical care. We sought to describe surgical care access among homeless patients in a Canadian tertiary care setting. Methods: We reviewed the medical records of adult (age > 18 yr) patients with no fixed address or a shelter address who presented to The Ottawa Hospital Emergency Department from Jan. 1, 2013, to Dec. 31, 2014, and required surgical referral. We analyzed the data using descriptive statistics. Results: A surgical referral was initiated in 129 emergency department visits for 97 patients (77 men [79%], mean age 46.7 yr). Most patients lived in shelters (77 [79%]) and had provincial health insurance (82 [84%]), but only 35 (36%) had a primary care physician. The mean number visits for any reason was 7.9 (standard deviation 13.7) (range 1­106). The majority of surgical referrals (83 [64.3%]) were for traumatic injuries, and the most frequently consulted service (52 [40.3%]) was orthopedic surgery. Just under half (48 [49%]) of referred patients attended at least 1 outpatient appointment, and only a third (33 [34%]) completed full follow-up. Conclusion: Homeless patients presenting to an emergency department and requiring surgical care were predominantly men living in shelters, most frequently seeking care for traumatic injuries. Current outpatient services may not meet the surgical care needs of these patients, as many do not access them. Alternative approaches to outpatient care must be considered, particularly among high-need services such as orthopedics, to support surgical care access among this population.


Contexte: L'utilisation des services de santé ambulatoires par les sans-abri est faible si on la compare à leurs besoins qui sont élevés; on ignore par contre s'il en va de même pour les soins chirurgicaux. Nous avons voulu décrire l'accès aux soins chirurgicaux chez les patients sans domicile fixe dans un hôpital de soins tertiaires au Canada. Méthodes: Nous avons passé en revue les dossiers médicaux de patients adultes (âge > 18 ans) sans domicile fixe ayant consulté aux urgences de l'Hôpital d'Ottawa entre le 1er janvier 2013 et le 31 décembre 2014, et pour qui une consultation en chirurgie avait été demandée. Nous avons analysé les données au moyen de statistiques descriptives. Résultats: Une consultation en chirurgie a été demandée lors de 129 visites aux urgences, pour 97 patients (77 hommes [79 %], âge moyen 46,7 ans). La plupart de ces patients vivaient dans des refuges (77 [79 %]) et bénéficiaient d'un régime d'assurance maladie provincial (82 [84 %]), mais seulement 35 (36 %) avaient un médecin de famille. Le nombre moyen de visites, toutes raisons confondues, a été de 7,9 (écart-type 13,7) (entre 1 et 106). La majorité des demandes de consultations en chirurgie (83 [64,3 %]) concernaient des lésions traumatiques et le service le plus souvent appelé en consultation (52 [40,3 %]) était la chirurgie orthopédique. Un peu moins de la moitié (48 [49 %]) des patients envoyés en consultation se sont présentés à au moins un rendez-vous en clinique externe, et seulement le tiers d'entre eux (33 [34 %]) se sont soumis au suivi complet. Conclusion: Les patients sans domicile fixe qui consultent aux urgences et ont besoin de soins chirurgicaux étaient principalement des hommes hébergés dans des refuges ayant le plus souvent consulté pour des blessures traumatiques. Les services ambulatoires actuels ne répondent peut-être pas aux besoins chirurgicaux de ces patients, car plusieurs n'y accèdent pas. Il faudrait envisager d'autres approches, particulièrement en ce qui concerne les services très en demande, comme l'orthopédie, pour faciliter l'accès aux soins chez cette population.


Assuntos
Procedimentos Cirúrgicos Ambulatórios/estatística & dados numéricos , Pessoas Mal Alojadas/psicologia , Pacientes Ambulatoriais/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Ferimentos e Lesões/cirurgia , Adulto , Procedimentos Cirúrgicos Ambulatórios/psicologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Pessoas Mal Alojadas/estatística & dados numéricos , Humanos , Seguro Saúde/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Ontário , Pacientes Ambulatoriais/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Centros Cirúrgicos/estatística & dados numéricos , Centros de Atenção Terciária/estatística & dados numéricos
16.
HPB (Oxford) ; 20(1): 69-75, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28927654

RESUMO

BACKGROUND: The level of utilization and acceptance of the 2005 International Study Group for Pancreatic Fistula (ISGPF) definition for postoperative pancreatic fistula (POPF) has not be quantified. The aim of this study was to determine the uptake of the ISGPF definition and evaluate its use in the surgical literature. METHODS: A sample of primary studies, review articles, and textbooks were identified through screening of literature searches. Included citations were assessed for their definition of POPF and use of the ISGPF criteria. RESULTS: From 2006 to 2009, 6%-63% of primary papers were compliant with the ISGPF definition compared to 84%-98% from 2010 onwards. Of the primary studies compliant with the ISGPF criteria, 36% focused on grade B and C fistula and 15% did not report grade A fistula. 88% of European papers used the criteria compared to 77% and 72% of Asian and North American papers, respectively (p = 0.033). 46% of review articles and textbooks did not define POPF. Among those that defined POPF, 74% cited the ISGPF definition exclusively while 26% mentioned other definitions. CONCLUSION: The ISGPF criteria have been widely adopted and accepted as the standard for defining POPF, although the utility of grade A fistulas is questionable.


Assuntos
Fístula Pancreática/classificação , Fístula Pancreática/diagnóstico , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/diagnóstico , Fidelidade a Diretrizes , Humanos , Fístula Pancreática/etiologia , Complicações Pós-Operatórias/etiologia , Guias de Prática Clínica como Assunto , Padrões de Prática Médica
17.
Cochrane Database Syst Rev ; 7: CD001884, 2017 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-28691229

RESUMO

BACKGROUND: Blood transfusion is administered during many types of surgery, but its efficacy and safety are increasingly questioned. Evaluation of the efficacy of agents, such as desmopressin (DDAVP; 1-deamino-8-D-arginine-vasopressin), that may reduce perioperative blood loss is needed. OBJECTIVES: To examine the evidence for the efficacy of DDAVP in reducing perioperative blood loss and the need for red cell transfusion in people who do not have inherited bleeding disorders. SEARCH METHODS: We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (2017, issue 3) in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (from 1937), the Transfusion Evidence Library (from 1980), and ongoing trial databases (all searches to 3 April 2017). SELECTION CRITERIA: We included randomised controlled trials comparing DDAVP to placebo or an active comparator (e.g. tranexamic acid, aprotinin) before, during, or immediately after surgery or after invasive procedures in adults or children. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified 65 completed trials (3874 participants) and four ongoing trials. Of the 65 completed trials, 39 focused on adult cardiac surgery, three on paediatric cardiac surgery, 12 on orthopaedic surgery, two on plastic surgery, and two on vascular surgery; seven studies were conducted in surgery for other conditions. These trials were conducted between 1986 and 2016, and 11 were funded by pharmaceutical companies or by a party with a commercial interest in the outcome of the trial.The GRADE quality of evidence was very low to moderate across all outcomes. No trial reported quality of life. DDAVP versus placebo or no treatmentTrial results showed considerable heterogeneity between surgical settings for total volume of red cells transfused (low-quality evidence) and for total blood loss (very low-quality evidence) due to large differences in baseline blood loss. Consequently, these outcomes were not pooled and were reported in subgroups.Compared with placebo, DDAVP may slightly decrease the total volume of red cells transfused in adult cardiac surgery (mean difference (MD) -0.52 units, 95% confidence interval (CI) -0.96 to -0.08 units; 14 trials, 957 participants), but may lead to little or no difference in orthopaedic surgery (MD -0.02, 95% CI -0.67 to 0.64 units; 6 trials, 303 participants), vascular surgery (MD 0.06, 95% CI -0.60 to 0.73 units; 2 trials, 135 participants), or hepatic surgery (MD -0.47, 95% CI -1.27 to 0.33 units; 1 trial, 59 participants).DDAVP probably leads to little or no difference in the total number of participants transfused with blood (risk ratio (RR) 0.96, 95% CI 0.86 to 1.06; 25 trials; 1806 participants) (moderate-quality evidence).Whether DDAVP decreases total blood loss in adult cardiac surgery (MD -135.24 mL, 95% CI -210.80 mL to -59.68 mL; 22 trials, 1358 participants), orthopaedic surgery (MD -285.76 mL, 95% CI -514.99 mL to -56.53 mL; 5 trials, 241 participants), or vascular surgery (MD -582.00 mL, 95% CI -1264.07 mL to 100.07 mL; 1 trial, 44 participants) is uncertain because the quality of evidence is very low.DDAVP probably leads to little or no difference in all-cause mortality (Peto odds ratio (pOR) 1.09, 95% CI 0.51 to 2.34; 22 trials, 1631 participants) or in thrombotic events (pOR 1.36, 95% CI, 0.85 to 2.16; 29 trials, 1984 participants) (both low-quality evidence). DDAVP versus placebo or no treatment for people with platelet dysfunctionCompared with placebo, DDAVP may lead to a reduction in the total volume of red cells transfused (MD -0.65 units, 95% CI -1.16 to -0.13 units; 6 trials, 388 participants) (low-quality evidence) and in total blood loss (MD -253.93 mL, 95% CI -408.01 mL to -99.85 mL; 7 trials, 422 participants) (low-quality evidence).DDAVP probably leads to little or no difference in the total number of participants receiving a red cell transfusion (RR 0.83, 95% CI 0.66 to 1.04; 5 trials, 258 participants) (moderate-quality evidence).Whether DDAVP leads to a difference in all-cause mortality (pOR 0.72, 95% CI 0.12 to 4.22; 7 trials; 422 participants) or in thrombotic events (pOR 1.58, 95% CI 0.60 to 4.17; 7 trials, 422 participants) is uncertain because the quality of evidence is very low. DDAVP versus tranexamic acidCompared with tranexamic acid, DDAVP may increase the volume of blood transfused (MD 0.6 units, 95% CI 0.09 to 1.11 units; 1 trial, 40 participants) and total blood loss (MD 142.81 mL, 95% CI 79.78 mL to 205.84 mL; 2 trials, 115 participants) (both low-quality evidence).Whether DDAVP increases or decreases the total number of participants transfused with blood is uncertain because the quality of evidence is very low (RR 2.42, 95% CI 1.04 to 5.64; 3 trials, 135 participants).No trial reported all-cause mortality.Whether DDAVP leads to a difference in thrombotic events is uncertain because the quality of evidence is very low (pOR 2.92, 95% CI 0.32 to 26.83; 2 trials, 115 participants). DDAVP versus aprotininCompared with aprotinin, DDAVP probably increases the total number of participants transfused with blood (RR 2.41, 95% CI 1.45 to 4.02; 1 trial, 99 participants) (moderate-quality evidence).No trials reported volume of blood transfused or total blood loss and the single trial that included mortality as an outcome reported no deaths.Whether DDAVP leads to a difference in thrombotic events is uncertain because the quality of evidence is very low (pOR 0.98, 95% CI 0.06 to 15.89; 2 trials, 152 participants). AUTHORS' CONCLUSIONS: Most of the evidence derived by comparing DDAVP versus placebo was obtained in cardiac surgery, where DDAVP was administered after cardiopulmonary bypass. In adults undergoing cardiac surgery, the reduction in volume of red cells transfused and total blood loss was small and was unlikely to be clinically important. It is less clear whether DDAVP may be of benefit for children and for those undergoing non-cardiac surgery. A key area for researchers is examining the effects of DDAVP for people with platelet dysfunction. Few trials have compared DDAVP versus tranexamic acid or aprotinin; consequently, we are uncertain of the relative efficacy of these interventions.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Desamino Arginina Vasopressina/administração & dosagem , Transfusão de Eritrócitos/estatística & dados numéricos , Hemostáticos/administração & dosagem , Adulto , Antifibrinolíticos/administração & dosagem , Aprotinina/administração & dosagem , Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Humanos , Procedimentos Ortopédicos/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido Tranexâmico/administração & dosagem , Transplante Homólogo , Procedimentos Cirúrgicos Vasculares/estatística & dados numéricos
18.
HPB (Oxford) ; 19(8): 675-681, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28495435

RESUMO

BACKGROUND: Recent advances in care for colorectal liver metastases (CRLM) have lengthened 5-year survival. In this new era, prognostic tools such as the clinical risk score (CRS) for colorectal liver metastases require reevaluation. METHODS: Patients undergoing resection for CRLM between 2008 and 2012 at 4 specialty hepatobiliary centers in Canada (N = 740) were stratified by CRS and analyzed in Kaplan-Meier survival curves. Primary outcome of overall survival (OS) and secondary outcome of recurrence-free survival (RFS). Multivariate Cox regression compared CRS to patient factors. RESULTS: Median OS not reached (>60 months), median RFS 16 months. Original CRS strata was a significant (p < 0.001) predictor of both OS (5-year OS: 0; 75%, 1; 71%, 2; 57%, 3; 57%, 4; 46%) and RFS (5-year RFS: 0; 39%, 1; 33%, 2; 21%, 3; 21%, 4; 8%). The presence of extrahepatic colorectal metastatic disease increased recurrence risk (RFS hazard ratio of 1.32 (1.06-1.65)), and the use of intraoperative portal pedicle clamping reduced recurrence risk (RFS hazard ratio of 0.78 (0.61-0.99)). CONCLUSIONS: The CRS remains a relevant tool for predicting long-term outcomes for patients undergoing resection of CRLM. Additional factors such as the presence of extrahepatic colorectal metastatic disease and the use of intraoperative portal pedicle clamping may improve the prognostic power of the CRS.


Assuntos
Neoplasias Colorretais/patologia , Técnicas de Apoio para a Decisão , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Metastasectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Canadá , Neoplasias Colorretais/mortalidade , Progressão da Doença , Intervalo Livre de Doença , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Metastasectomia/efeitos adversos , Metastasectomia/mortalidade , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
19.
HPB (Oxford) ; 19(4): 321-330, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28161216

RESUMO

BACKGROUND: Liver resection is associated with a high proportion of red blood cell transfusions. There is a proposed association between perioperative transfusions and increased risk of complications and tumor recurrence. This study reviews the evidence of this association in the literature. METHODS: The Medline, EMBASE, and Cochrane databases were searched for clinical trials or observational studies of patients undergoing liver resection that compared patients who did and did not receive a perioperative red blood cell transfusion. Outcomes were mortality, complications, and cancer survival. RESULTS: Twenty-two studies involving 6832 patients were included. All studies were retrospective, with no clinical trials. No studies were scored as low risk of bias. The overall proportion of patients transfused was 38.3%. After multivariate analysis, 1 of 5 studies demonstrated an association between transfusion and increased mortality; 5 of 6 demonstrated an association between transfusion and increased complications; and 10 of 18 demonstrated an association between transfusion and decreased cancer survival. CONCLUSION: This review supports the evidence linking perioperative blood transfusions to negative outcomes. The most convincing association was with post-operative complications, some association with long-term cancer outcomes, and no convincing association with mortality. These findings support the initiation, and further study, of restrictive transfusion protocols.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Eritrócitos/efeitos adversos , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/cirurgia , Hemorragia Pós-Operatória/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/mortalidade , Transfusão de Eritrócitos/mortalidade , Feminino , Hepatectomia/mortalidade , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Razão de Chances , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/mortalidade , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
BMC Cancer ; 16(1): 786, 2016 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-27724927

RESUMO

BACKGROUND: Pancreatic cancer is among the top 5 most common cancers worldwide, but is particularly devastating due to its insidious nature. Complete surgical resection remains the only potential curative treatment, although only 20 % of patients present with a resectable tumor. Patients may alternatively present with borderline resectable pancreatic cancer or locally advanced pancreatic cancer and can be offered treatment with neoadjuvant intent. The effectiveness of these treatments is unclear and there is a paucity of data to suggest one optimal treatment approach. CASE PRESENTATION: We describe a 61-year-old female who presented with a two-week history of obstructive jaundice in the context of vague abdominal pain that had been ongoing for years prior to her visit. CT scan of the abdomen confirmed a hypovascular mass in the uncinate process consistent with borderline resectable pancreatic cancer. Pancreatic adenocarcinoma was confirmed with endoscopic ultrasound guided fine-needle aspiration cytology. Following multidisciplinary discussion, it was recommended that she undergo treatment with FOLFIRINOX. After a total of 13 cycles, follow up CT revealed that the lesion had decreased in size and she was offered resection as a potentially curative treatment. She underwent pancreaticoduodenectomy. Final pathology report revealed no evidence of residual adenocarcinoma (ypT0 ypN0 (0/23)). The patient remains disease-free 15 months following surgery. CONCLUSION: To date, there have been very few reports of a complete pathological response following neoadjuvant therapy in borderline resectable or locally advanced pancreatic cancer. This report describes a unique case of a complete pathological remission in a patient with borderline resectable pancreatic cancer following FOLFIRINOX therapy alone and adds to the growing base of evidence meriting the initiation of clinical trials to assess the efficacy of FOLFIRINOX in these subsets of pancreatic cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/tratamento farmacológico , Colangiopancreatografia Retrógrada Endoscópica , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Neoplasias Pancreáticas
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