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BACKGROUND: Induced pluripotent stem cells (iPSCs) offer the potential to generate autologous iPSC-derived islets (iPSC islets), however, remain limited by scalability and product safety. METHODS: Herein, we report stagewise characterization of cells generated following a bioreactor-based differentiation protocol. Cell characteristics were assessed using flow cytometry, quantitative reverse transcription polymerase chain reaction, patch clamping, functional assessment, and in vivo functional and immunohistochemistry evaluation. Protocol yield and costs are assessed to determine scalability. RESULTS: Differentiation was capable of generating 90.4% PDX1+/NKX6.1+ pancreatic progenitors and 100% C-peptide+/NKX6.1+ iPSC islet cells. However, 82.1%, 49.6%, and 0.9% of the cells expressed SOX9 (duct), SLC18A1 (enterochromaffin cells), and CDX2 (gut cells), respectively. Explanted grafts contained mature monohormonal islet-like cells, however, CK19+ ductal tissues persist. Using this protocol, semi-planar differentiation using 150 mm plates achieved 5.72 × 104 cells/cm2 (total 8.3 × 106 cells), whereas complete suspension differentiation within 100 mL Vertical-Wheel bioreactors significantly increased cell yield to 1.1 × 106 cells/mL (total 105.0 × 106 cells), reducing costs by 88.8%. CONCLUSIONS: This study offers a scalable suspension-based approach for iPSC islet differentiation within Vertical-Wheel bioreactors with thorough characterization of the ensuing product to enable future protocol comparison and evaluation of approaches for off-target cell elimination. Results suggest that bioreactor-based suspension differentiation protocols may facilitate scalability and clinical implementation of iPSC islet therapies.
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BACKGROUND: Efforts to preoperatively risk stratify and optimize patients before pancreaticoduodenectomy continue to improve outcomes. This study aims to determine the impact of hypoalbuminemia on outcomes following pancreaticoduodenectomy and outline optimal hypoalbuminemia cut-off values in this population. METHODS: The ACS-NSQIP (2016-2021) database was used to extract patients who underwent pancreaticoduodenectomy, comparing those with hypoalbuminemia (< 3.0 g/L) to those with normal albumin. Demographics and 30-day outcomes were compared. Multivariable modeling evaluated factors including hypoalbuminemia to characterize their independent effect on serious complications, and mortality. Optimal albumin cut-offs for serious complications and mortality were evaluated using receiver-operating characteristic curves. RESULTS: We evaluated 25,848 pancreaticoduodenectomy patients with 2712 (10.5%) having preoperative hypoalbuminemia. Patients with hypoalbuminemia were older (68.2 vs. 65.1; p < 0.0001), and were significantly more likely to be ASA class 4 or higher (13.9% vs. 6.7%; p < 0.0001). Patients with hypoalbuminemia had significantly more 30-day complications and after controlling for comorbidities hypoalbuminemia remained a significant independent factor associated with 30-day serious complications (OR 1.80, p < 0.0001) but not mortality (OR 1.37, p = 0.152). CONCLUSIONS: Hypoalbuminemia plays a significant role in 30-day morbidity following pancreaticoduodenectomy. Preoperative albumin may serve as a useful marker for risk stratification and optimization.
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BACKGROUND: Biliary obstruction before liver resection is a known risk factor for post-operative complications. The aim of this study was to determine the impact of persistent hyperbilirubinemia following preoperative biliary drainage before liver resection. METHODS: The ACS-NSQIP (2016-2021) database was used to extract patients with cholangiocarcinoma who underwent anatomic liver resection with preoperative biliary drainage comparing those with persistent hyperbilirubinemia (> 1.2 mg/dL) to those with resolution. Patient characteristics and outcomes were compared with bivariate analysis. Multivariable modeling evaluated factors including persistent hyperbilirubinemia to evaluate their independent effect on serious complications, liver failure, and mortality. RESULTS: We evaluated 463 patients with 217 (46.9%) having hyperbilirubinemia (HB) despite biliary stenting. Bivariate analysis demonstrated that patients with HB had a higher rate of serious complications than those with non-HB (80.7% vs 70.3%; P = 0.010) including bile leak (40.9% vs 31.8%; P = 0.045), liver failure (26.7% vs 17.9%; P = 0.022), and bleeding (48.4% vs 36.6%; P = 0.010). Multivariable analysis demonstrated that persistent HB was independently associated with serious complications (OR 1.88, P = 0.020) and mortality (OR 2.39, P = 0.049) but not post-operative liver failure (OR 1.65, P = 0.082). CONCLUSIONS: Failed preoperative biliary decompression is a predictive factor for post-operative complications and mortality in patients undergoing hepatectomy and may be useful for preoperative risk stratification.
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Hepatectomia , Hiperbilirrubinemia , Complicações Pós-Operatórias , Cuidados Pré-Operatórios , Stents , Humanos , Feminino , Masculino , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Hiperbilirrubinemia/etiologia , Estudos Retrospectivos , Cuidados Pré-Operatórios/métodos , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/complicações , Drenagem/métodos , Colangiocarcinoma/cirurgia , Colangiocarcinoma/complicações , Colestase/etiologia , Colestase/cirurgia , Fatores de RiscoRESUMO
BACKGROUND: Anastomotic leak after esophagectomy is a major contributor to surgery-related morbidity and mortality. The purpose of this systematic review was to evaluate if positive-smoking status is associated with the incidence of this complication. METHODS: A systematic search of MEDLINE, EMBASE, Scopus, Web of Science and Cochrane Library was performed on April 4th, 2023. Inclusion criteria comprised human participants undergoing esophagectomy, age ≥ 18, n ≥ 5, and identification of smoking status. The primary outcome was incidence of anastomotic leak. Sub-group analysis by ex- or current smoking status was performed. Meta-analysis was performed with RevMan 5.4.1 using a Mantel-Haenszel random-effects model. Publication bias was evaluated visually with funnel plots and through the Egger test. RESULTS: A total of 220 abstracts were screened, of which 69 full-text studies were assessed for eligibility, with 13 studies selected for final inclusion. This included 16,103 patients, of which 4433 were ex- or current smokers, and 9141 were never smokers. Meta-analysis revealed an increased odds of anastomotic leak in patients with a positive-smoking status (current or ex-smokers) compared to never smokers (OR 1.44, 95% CI 1.18-1.76, I2 = 44%, p < 0.001. Meta-analysis of six studies comparing active smokers alone to never smokers identified a significant increased odds of anastomotic leak (OR 1.80, 95% CI 1.25-2.59, p = 0.002, I2 = 0%). Meta-analysis of five studies comparing ex-smokers to never smokers identified a significant increased odds of anastomotic leak (OR 1.36, 95% CI 1.02-1.82, p = 0.04, I2 = 0%). The odds of anastomotic leak decreased among ex-smokers compared to active smokers. CONCLUSION: The findings of this systematic review and meta-analysis support the association between positive-smoking status and the risk of anastomotic leak after esophagectomy. Results further emphasize the importance of preoperative smoking cessation to reduce post-operative morbidity.
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Fístula Anastomótica , Esofagectomia , Fumar , Fístula Anastomótica/etiologia , Fístula Anastomótica/epidemiologia , Humanos , Esofagectomia/efeitos adversos , Fumar/efeitos adversos , Fumar/epidemiologia , Neoplasias Esofágicas/cirurgia , Fatores de Risco , IncidênciaRESUMO
Background: Limited information is available regarding outcomes of islet cell isolation (ICI) and transplantation (ITx) using medical assistance in dying (MAiD) donors. We aimed to assess the feasibility and outcomes of ICI and ITx in MAiD donors. Methods: ICI and ITx from MAiD were compared with donation after circulatory death (DCD) type III between 2016 and 2023. Differences of isolated islet equivalents (IEQs), numeric viability and other quantitative in vitro metabolic measures were assessed. Results: Overall, 81 ICIs were available of whom 34 (42%) and 47 (58%) from MAiD and DCD-III, respectively. There were no differences of pancreas and digested tissue weight and islets viability among the 2 groups; however, cold ischemic time was longer in MAiD (11.5 versus 9.1 h; Pâ =â 0.021). The IEQ (Pâ <â 0.001) and percent trapped (Pâ <â 0.001) were higher in the DCD-III; however, MAiD islets demonstrated a higher purity (Pâ =â 0.020). Overall, 15 ITx were performed of whom 3 (8.8%) and 12 (25.5%) from MAiD and DCD-III, respectively (Pâ =â 0.056). Patients had a median fasting C-peptide of 0.51 ng/mL (interquartile range, 0.30-0.76 nmol/L), with no differences between groups (MAiD = 0.52 versus DCD-III = 0.51; Pâ =â 0.718). The median HbA1c was 6.2% (interquartile range, 5.7%-7%) (MAiD = 6.3% versus DCD-III = 6.1%; Pâ =â 0.815) and BETA2 scores (MAiD = 7.4 versus DCD-III = 12.8; Pâ =â 0.229) did not differ. Conclusions: ICI from MAiD donor pancreas may be successfully transplanted with comparable outcomes to DCD-III and may be used for research. These results justify additional efforts to consider MAiD as another valuable source of grafts for ITx. Further multicenter studies and larger clinical experience are needed to validate our findings.
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Demografia , Humanos , Feminino , Masculino , Coleta de Dados , Grupos Minoritários/estatística & dados numéricos , CanadáRESUMO
BACKGROUND: Studies have evaluated the efficacy of endoscopic incisional therapy (EIT) for benign anastomotic strictures. We performed a systematic review and meta-analysis to evaluate stricture recurrence after EIT following esophagectomy or gastrectomy. METHODS: A systematic search of databases was performed up to April 2nd, 2023, after selection of key search terms with the research team. Inclusion criteria included human participants undergoing EIT for a benign anastomotic stricture after esophagectomy or gastrectomy, age ≥ 18, and n ≥ 5. Our primary outcome was the incidence of stricture recurrence among patients treated with EIT compared to dilation. Our secondary outcome was the stricture-free duration after EIT and rate of adverse events. Meta-analysis was performed with RevMan 5.4.1 using a Mantel-Haenszel random-effects model. Publication bias was evaluated with funnel plots and the Egger test. RESULTS: A total of 2550 unique preliminary studies underwent screening of abstracts and titles. This led to 33 studies which underwent full-text review and five studies met the inclusion criteria. Meta-analysis revealed reduced odds of overall stricture recurrence (OR 0.35, 95% CI 0.13-0.92, p = 0.03; I2 = 71%) and reduced odds of stricture recurrence among naïve strictures (OR 0.32, 95% CI 0.17-0.59, p = 0.0003; I2 = 0%) for patients undergoing EIT compared to dilation. There was no significant difference in the odds of stricture recurrence among recurrent strictures (OR 0.63, 95% CI 0.12-3.28, p = 0.58; I2 = 81%). Meta-analysis revealed a significant increase in the recurrence-free duration (MD 42.76, 95% CI 12.41-73.11, p = 0.006) among patients undergoing EIT compared to dilation. CONCLUSION: Current data suggest EIT is associated with reduced odds of stricture recurrence among naïve anastomotic strictures. Large, prospective studies are needed to characterize the safety profile of EIT, address publication bias, and to explore multimodal therapies for refractory strictures.
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Anastomose Cirúrgica , Estenose Esofágica , Esofagectomia , Gastrectomia , Complicações Pós-Operatórias , Humanos , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Anastomose Cirúrgica/efeitos adversos , Estenose Esofágica/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Constrição Patológica/etiologia , Recidiva , Dilatação/métodosRESUMO
INTRODUCTION: Gastroesophageal reflux disease (GERD) is a well-established potential consequence of bariatric surgery and can require revisional surgery. Our understanding of the population requiring revision is limited. In this study, we aim to characterize patients requiring revisional surgery for GERD to understand their perioperative risks and identify strategies to improve their outcomes. METHODS: Using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) registry, a retrospective cohort of patients who required revisional surgery for GERD in 2020 was identified. Multivariable logistic regression modelling was used to assess correlations between baseline characteristics and morbidity. RESULTS: 4412 patients required revisional surgery for GERD, encompassing 24% of all conversion procedures. In most cases, patients underwent sleeve gastrectomy (SG) as their original surgery (n = 3535, 80.1%). The revisional surgery for most patients was a Roux-en-Y gastric bypass (RYGB) (n = 3722, 84.4%). Major complications occurred in 527 patients (11.9%) and 10 patients (0.23%) died within 30 days of revisional surgery. Major complications included anastomotic leak in 31 patients (0.70%) and gastrointestinal bleeding in 38 patients (0.86%). Multivariable analyses revealed that operative length, pre-operative antacid use, and RYGB were predictors of major complications. CONCLUSION: GERD is the second most common indication for revisional surgery in patients who have undergone bariatric surgery. Patients who underwent SG as their initial procedure were the primary group who required revisional surgery for GERD; most underwent revision via RYGB. Further inquiry is needed to tailor operative approaches and pre-operative optimization for revisional surgery patients.
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Cirurgia Bariátrica , Derivação Gástrica , Refluxo Gastroesofágico , Laparoscopia , Obesidade Mórbida , Humanos , Estudos Retrospectivos , Reoperação/efeitos adversos , Redução de Peso , Derivação Gástrica/métodos , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/métodos , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/cirurgia , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Obesidade Mórbida/cirurgia , Resultado do Tratamento , Laparoscopia/métodosRESUMO
Background: Medical student interest in surgical specialties continues to decline. This study aims to characterize attitudes of Canadian medical students towards surgical training and perceived barriers to surgical careers. Methods: An anonymous survey was custom designed and distributed to medical students at the University of Alberta and University of Calgary. Survey questions characterized student interest in surgical specialties, barriers to pursuing surgery, and influence of surgical education opportunities on career interest. Results: Survey engagement was 26.7% in 2015 and 24.2% in 2021. General surgery had the highest rate of interest in both survey years (2015: 38.3%, 2021: 39.2%). The most frequently reported barrier was worry about the stress that surgical careers can put on personal relationships (2015: 70.9%, 2021: 73.8%, p= 0.50). Female respondents were significantly more likely to cite gender discrimination as a deterrent to surgical careers (F: 52.0%, M: 5.8%, p < 0.001). Conclusions: Despite substantial interest, perception of work-life imbalance was the primary reported barrier to surgical careers. Further, female medical students' awareness of gender discrimination in surgery highlights the need for continued efforts to promote gender inclusivity within surgical disciplines to support early career women interested in surgery.
Contexte: L'intérêt des étudiants en médecine canadiens pour les spécialités chirurgicales est en diminution constante. Cette étude vise à caractériser leurs attitudes à l'égard de la formation en chirurgie et les obstacles qu'ils perçoivent à la poursuite d'une carrière dans cette discipline. Méthodes: Un sondage anonyme conçu sur mesure a été distribué aux étudiants en médecine de l'Université de l'Alberta et de l'Université de Calgary. Les questions de l'enquête portaient sur leur intérêt pour les spécialités chirurgicales, sur ce qui les empêche de les choisir comme voie de carrière et sur l'influence des possibilités de formation en chirurgie sur leur intérêt à suivre une carrière dans ces spécialités. Résultats: Le taux de participation à l'enquête était de 26,7 % en 2015 et de 24,2 % en 2021. La spécialité qui a recueilli le taux d'intérêt le plus élevé était la chirurgie générale, et ce pour les deux années d'enquête (2015 : 38,3 %, 2021 : 39,2 %). L'obstacle le plus fréquemment cité était la difficile conciliation entre la vie personnelle et les exigences des carrières chirurgicales (2015 : 70,9 %, 2021 : 73,8 %, p = 0,50). Les femmes interrogées étaient significativement plus susceptibles de citer la discrimination fondée sur le sexe comme frein au choix d'une carrière chirurgicale (F : 52,0 %, M : 5,8 %, p < 0,001). Conclusions: Malgré un intérêt considérable, la perception d'un déséquilibre entre la vie professionnelle et la vie personnelle est le principal obstacle déclaré au choix d'une carrière dans le domaine de la chirurgie. De plus, la discrimination sexuelle perçue par les étudiantes dans la discipline souligne le besoin d'efforts soutenus pour promouvoir l'inclusivité des sexes dans les spécialités chirurgicales afin de soutenir les femmes en début de carrière qui s'intéressent à la chirurgie.
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Estudantes de Medicina , Feminino , Humanos , Atitude , Canadá , Escolha da Profissão , Inquéritos e Questionários , MasculinoRESUMO
Mitochondria are the powerhouse of the cell and dynamically control fundamental biological processes including cell reprogramming, pluripotency, and lineage specification. Although remarkable progress in induced pluripotent stem cell (iPSC)-derived cell therapies has been made, very little is known about the role of mitochondria and the mechanisms involved in somatic cell reprogramming into iPSC and directed reprogramming of iPSCs in terminally differentiated cells. Reprogramming requires changes in cellular characteristics, genomic and epigenetic regulation, as well as major mitochondrial metabolic changes to sustain iPSC self-renewal, pluripotency, and proliferation. Differentiation of autologous iPSC into terminally differentiated ß-like cells requires further metabolic adaptation. Many studies have characterized these alterations in signaling pathways required for the generation and differentiation of iPSC; however, very little is known regarding the metabolic shifts that govern pluripotency transition to tissue-specific lineage differentiation. Understanding such metabolic transitions and how to modulate them is essential for the optimization of differentiation processes to ensure safe iPSC-derived cell therapies. In this review, we summarize the current understanding of mitochondrial metabolism during somatic cell reprogramming to iPSCs and the metabolic shift that occurs during directed differentiation into pancreatic ß-like cells.
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Epigênese Genética , Células-Tronco Pluripotentes , Humanos , Diferenciação Celular , Reprogramação Celular , Células-Tronco Pluripotentes/metabolismo , Mitocôndrias/metabolismoRESUMO
Generation of pure pancreatic progenitor (PP) cells is critical for clinical translation of stem cell-derived islets. Herein, we performed PP differentiation with and without AKT/P70 inhibitor AT7867 and characterized the resulting cells at protein and transcript level in vitro and in vivo upon transplantation into diabetic mice. AT7867 treatment increased the percentage of PDX1+NKX6.1+ (-AT7867: 50.9% [IQR 48.9%-53.8%]; +AT7867: 90.8% [IQR 88.9%-93.7%]; p = 0.0021) and PDX1+GP2+ PP cells (-AT7867: 39.22% [IQR 36.7%-44.1%]; +AT7867: 90.0% [IQR 88.2%-93.6%]; p = 0.0021). Transcriptionally, AT7867 treatment significantly upregulated PDX1 (p = 0.0001), NKX6.1 (p = 0.0005), and GP2 (p = 0.002) expression compared with controls, while off-target markers PODXL (p < 0.0001) and TBX2 (p < 0.0001) were significantly downregulated. Transplantation of AT7867-treated PPs resulted in faster hyperglycemia reversal in diabetic mice compared with controls (time and group: p < 0.0001). Overall, our data show that AT7867 enhances PP cell differentiation leading to accelerated diabetes reversal.
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Diabetes Mellitus Experimental , Células-Tronco Pluripotentes Induzidas , Células Secretoras de Insulina , Humanos , Animais , Camundongos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diferenciação Celular , Pâncreas , Células-Tronco Pluripotentes Induzidas/metabolismo , Células Secretoras de Insulina/metabolismoRESUMO
BACKGROUND: Job competition and underemployment among surgeons emphasize the importance of equitable hiring practices. The purpose of this study was to describe some of the demographic characteristics of academic general surgeons and to evaluate the gender and visible minority (VM) status of those recently hired. METHODS: Demographic information about academic general surgeons across Canada including gender, VM status, practice location and graduate degree status was collected. Location of residency was collected for recently hired general surgeons (hired between 2013 and 2020). Descriptive statistics were performed on the demographic characteristics at each institution. Pearson correlation coefficients and hypothesis testing were used to determine the correlation between various metrics and gender and VM status. RESULTS: A total of 393 general surgeons from 30 academic hospitals affiliated with 14 universities were included. The percentage of female general surgeons ranged from 0% to 47.4% and the percentage of VM general surgeons ranged from 0% to 66.7% at the hospitals. This heterogeneity did not correlate with city population (gender: r = 0.06, p = 0.77; VM: r = 0.04, p = 0.83). The percentage of VM general surgeons at each hospital did not correlate with the percentage of VM population in the city (r = 0.13, p = 0.49). Only 34 of 120 recently hired academic general surgeons (28.3%) did not have a graduate degree. The percentage of recently hired academic general surgeons who did not have a graduate degree was approximately 1.5 times higher among male hirees than female hirees. With respect to academic promotion, the percentage of female full professors ranged from 0% to 40.0% and did not correlate with the percentage of female general surgeons at each institution (r = 0.11, p = 0.70). The percentage of VM full professors ranged from 0% to 44.4% and was moderately correlated with the percentage of VM surgeons at each institution (r = 0.40, p = 0.16). CONCLUSION: The academic general surgery workforce appears to be somewhat diverse. However, there was substantial heterogeneity in diversity between hospitals, leaving room for improvement. We must be willing to examine our hiring processes and be transparent about them to build an equitable surgical workforce.
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Cirurgiões , Humanos , Feminino , Masculino , Canadá , Hospitais , Benchmarking , EmpregoRESUMO
BACKGROUND: Recruiting residents to practise rurally begins with an accurate characterization of rural surgeons. We sought to identify and analyze demographic trends among rural surgeons in Canada and to predict the rural workforce requirements for the next decade. METHODS: In this retrospective observational study, we assessed the demographic and practice characteristics of rural general surgeons in Canada, defined as surgeons working in cities with a population of 100 000 or less. Surgeons were identified using the websites of provincial colleges of physicians and surgeons. Demographic characteristics included year and country of medical degree achievement, fellowship status and primary practice location. We developed a model predicting future rural workforce requirements based on the following assumptions: that the current ratio of rural surgeons to rural patients is adequate, that the rural population will increase by 1.1% annually, that a rural surgeon's career length is 36 years, and that 85 graduates will enter the workforce annually. RESULTS: Our study sample included 760 rural general surgeons. The majority graduated after 1989 (75%), were Canadian medical graduates (73%) and did not complete a fellowship (82%). There was a significant shift toward rural surgeons being trained in Canada, from 37% of surgeons graduating before 1969 to 91% of those graduating after 2009 (p < 0.001). Modelling predicts 282 rural general surgeons will retire by 2031, with 88 new surgeons needed to account for the population growth. Therefore, we predict a demand for 370 rural surgeons over the next decade, meaning 43% of general surgery graduates will need to enter rural practice. CONCLUSION: Rural general surgeons in Canada vary widely in their background demographic characteristics. Future opportunities in rural general surgery are projected to increase. Recruitment and training of general surgery graduates to serve Canada's rural communities remains essential.
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População Rural , Cirurgiões , Humanos , Canadá , Bolsas de Estudo , AposentadoriaRESUMO
BACKGROUND: The Metabolic and Bariatric Accreditation and Quality Improvement Program (MBSAQIP) Bariatric Surgical Risk/Benefit Calculator was developed to provide patient-specific information to assist surgical decision-making. To date, no study has characterized which patients are being evaluated with this tool. OBJECTIVE: We sought to characterize the use and impact of the MBSAQIP calculator. SETTING: MBSAQIP collects data from 955 centers in North America. METHODS: The 2021 MBSAQIP database was evaluated for the use of the calculator on preoperative counseling for patients undergoing bariatric surgery. Patient characteristics, operative techniques, and outcomes were compared with bivariate analysis. Multivariable modeling evaluated factors including use of the calculator independently associated with serious complications and mortality. RESULTS: Our study included 210,710 patients, 35,158 (16.7%) of whom were evaluated using the calculator. Patients with whom the calculator was used preoperatively were older (43.8 ± 11.6 yr versus 43.6 ± 11.7 yr; P < .001) and were more likely to have insulin-dependent diabetes, hypertension, gastroesophageal reflux disease, renal insufficiency, and sleep apnea. More patients underwent Roux-en-Y gastric bypass in the calculator cohort compared with the cohort that did not use the calculator (29.6% versus 28.6%; P < .003). The rate of serious complication was significantly less in the calculator cohort (3.1% versus 3.4%; P < .030). Multivariable modeling evaluating serious complications showed that use of the calculator was independently associated with reduced risk of serious complications (odds ratio .87, CI .82-.93, P < .001) but was not associated with mortality. CONCLUSION: The use of the risk calculator may help to reduce the incidence of complications by opening a dialogue between healthcare professionals and patients, setting realistic expectations, and identifying modifiable risk factors.
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INTRODUCTION: Endoscopic plication offers an alternative to surgical fundoplication for treatment of gastroesophageal reflux disease (GERD). This systematic review and meta-analysis evaluate outcomes following endoscopic plication compared to laparoscopic fundoplication. METHODS AND PROCEDURES: Systematic search of MEDLINE, Embase, Scopus, and Web of Science was conducted in September 2022. Study followed PRISMA guidelines. Studies comparing endoscopic plication to laparoscopic fundoplication with n > 5 were included. Primary outcome was PPI cessation, with secondary outcomes including complications, procedure duration, length of stay, change in lower esophageal sphincter (LES) tone, and DeMeester score. RESULTS: We reviewed 1544 studies, with five included comparing 105 (46.1%) patients receiving endoscopic plication (ENDO) to 123 (53.9%) undergoing laparoscopic fundoplication (LAP). Average patient age was 47.6 years, with those undergoing plication being younger (46.4 ENDO vs 48.5 LAP). BMI (26.6 kg/m2 ENDO vs 26.2 kg/m2 LAP), and proportion of females (42.9% ENDO vs 37.4% LAP) were similar. Patients undergoing laparoscopic procedures had worse baseline LES pressure (12.8 mmHg ENDO vs 9.0 mmHg LAP) and lower preoperative DeMeester scores (34.6 ENDO vs. 34.1 LAP). The primary outcome demonstrated that 89.2% of patients undergoing laparoscopic fundoplication discontinued PPI compared to 69.4% for those receiving plication. Meta-analysis revealed that plication had significantly reduced odds of PPI discontinuation (OR 0.27, studies = 3, 95% CI 0.12 to 0.64, P = 0.003, I2 = 0%). Secondary outcomes demonstrated that odds of complications (OR 1.46, studies = 4, 95% CI 0.34 to 6.32, P = 0.62, I2 = 0%), length of stay (MD - 1.37, studies = 3, 95% CI - 3.48 to 0.73, P = 0.20, I2 = 94%), and procedure durations were similar (MD 0.78, studies = 3, 95% CI - 39.70 to 41.26, P = 0.97, I2 = 98%). CONCLUSIONS: This is the first meta-analysis comparing endoscopic plication to laparoscopic fundoplication. Results demonstrate greater likelihood of PPI discontinuation with laparoscopic fundoplication with similar post-procedural risk.
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Refluxo Gastroesofágico , Laparoscopia , Feminino , Humanos , Pessoa de Meia-Idade , Fundoplicatura/métodos , Resultado do Tratamento , Refluxo Gastroesofágico/etiologia , Esfíncter Esofágico Inferior/cirurgia , Laparoscopia/métodosRESUMO
BACKGROUND: Induced pluripotent stem cells (iPSCs) offer potential to revolutionize regenerative medicine as a renewable source for islets, dopaminergic neurons, retinal cells, and cardiomyocytes. However, translation of these regenerative cell therapies requires cost-efficient mass manufacturing of high-quality human iPSCs. This study presents an improved three-dimensional Vertical-Wheel® bioreactor (3D suspension) cell expansion protocol with comparison to a two-dimensional (2D planar) protocol. METHODS: Sendai virus transfection of human peripheral blood mononuclear cells was used to establish mycoplasma and virus free iPSC lines without common genetic duplications or deletions. iPSCs were then expanded under 2D planar and 3D suspension culture conditions. We comparatively evaluated cell expansion capacity, genetic integrity, pluripotency phenotype, and in vitro and in vivo pluripotency potential of iPSCs. RESULTS: Expansion of iPSCs using Vertical-Wheel® bioreactors achieved 93.8-fold (IQR 30.2) growth compared to 19.1 (IQR 4.0) in 2D (p < 0.0022), the largest expansion potential reported to date over 5 days. 0.5 L Vertical-Wheel® bioreactors achieved similar expansion and further reduced iPSC production cost. 3D suspension expanded cells had increased proliferation, measured as Ki67+ expression using flow cytometry (3D: 69.4% [IQR 5.5%] vs. 2D: 57.4% [IQR 10.9%], p = 0.0022), and had a higher frequency of pluripotency marker (Oct4+Nanog+Sox2+) expression (3D: 94.3 [IQR 1.4] vs. 2D: 52.5% [IQR 5.6], p = 0.0079). q-PCR genetic analysis demonstrated a lack of duplications or deletions at the 8 most commonly mutated regions within iPSC lines after long-term passaging (> 25). 2D-cultured cells displayed a primed pluripotency phenotype, which transitioned to naïve after 3D-culture. Both 2D and 3D cells were capable of trilineage differentiation and following teratoma, 2D-expanded cells generated predominantly solid teratomas, while 3D-expanded cells produced more mature and predominantly cystic teratomas with lower Ki67+ expression within teratomas (3D: 16.7% [IQR 3.2%] vs.. 2D: 45.3% [IQR 3.0%], p = 0.002) in keeping with a naïve phenotype. CONCLUSION: This study demonstrates nearly 100-fold iPSC expansion over 5-days using our 3D suspension culture protocol in Vertical-Wheel® bioreactors, the largest cell growth reported to date. 3D expanded cells showed enhanced in vitro and in vivo pluripotency phenotype that may support more efficient scale-up strategies and safer clinical implementation.
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Células-Tronco Pluripotentes Induzidas , Teratoma , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Antígeno Ki-67/metabolismo , Leucócitos Mononucleares , Diferenciação Celular/genética , FenótipoRESUMO
Historically, only patients with brittle diabetes or severe recurrent hypoglycemia have been considered for islet transplantation (ITx). This population has been selected to optimize the risk-benefit profile, considering risks of long-term immunosuppression and limited organ supply. However, with the advent of stem cell (SC)-derived ITx and the potential for immunosuppression-free ITx, consideration of a broader recipient cohort may soon be justified. Simultaneously, the classical categorization of diabetes is being challenged by growing evidence in support of a clustering of disease subtypes that can be better categorized by the All New Diabetics in Scania (ANDIS) classification system. Using the ANDIS classification, 5 subtypes of diabetes have been described, each with unique causes and consequences. We evaluate consideration for ITx in the context of this broader patient population and the new classification of diabetes subtypes. In this review, we evaluate considerations for ITx based on novel diabetes subtypes, including their limitations, and we elaborate on unique transplant features that should now be considered to enable ITx in these "unconventional" patient cohorts. Based on evidence from those receiving whole pancreas transplant and our more than 20-year experience with ITx, we offer recommendations and potential research avenues to justify implementation of SC-derived ITx in broader populations of patients with all types of diabetes.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hipoglicemia , Transplante das Ilhotas Pancreáticas , Transplante de Pâncreas , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/cirurgia , Diabetes Mellitus Tipo 1/cirurgia , Hipoglicemia/epidemiologiaRESUMO
This systematic review and meta-analysis evaluates metabolic and anthropometric outcomes of duodenal-jejunal bypass liners (DJBLs) compared to optimal medical management for the treatment of obesity and its associated metabolic complications. A systematic search of MEDLINE, Embase, Scopus, and Web of Science databases was conducted. Studies were reviewed and data were extracted following the PRISMA guidelines. The primary outcome was glycated hemoglobin (HbA1c) change at device explant with secondary outcomes including body mass index (BMI), weight, fasting plasma glucose (FPG), and adverse events. Twenty-eight studies met inclusion criteria evaluating a total of 1229 patients undergoing DJBL treatment. When compared to medical management, DJBLs provided superior reductions in HbA1c (mean difference, MD -0.96%; 95% CI -1.43, -0.49; p < 0.0001), FPG (MD -1.76 mmol/L; 95% CI -2.80, -0.72; p = 0.0009), BMI (MD -2.80 kg/m2 ; 95% CI -4.18, -1.41; p < 0.0001), and weight (MD -5.45 kg; 95% CI -9.80, -1.09, p = 0.01). Post-explant data reveals a gradual return to baseline status. Incidence of early device explant was 20.2%. Complications were resolved conservatively or with device explant without long-term morbidity or mortality. We conclude that DJBLs provide significant metabolic and anthropometric improvements for patients with obesity. Uncertainty about the extent to which improvements are maintained after device removal may limit the use of DJBLs as a standalone treatment for obesity and associated metabolic complications.
Assuntos
Diabetes Mellitus Tipo 2 , Jejuno , Humanos , Jejuno/cirurgia , Hemoglobinas Glicadas , Duodeno/cirurgia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/cirurgia , Resultado do Tratamento , Obesidade/complicaçõesRESUMO
PURPOSE: Post-operative pneumonia after esophagectomy is a major contributor to morbidity and mortality. Prior studies have demonstrated a link between the presence of pathologic oral flora and the development of aspiration pneumonia. The objective of this systematic review and meta-analysis was to evaluate the effect of pre-operative oral care on the incidence of post-operative pneumonia after esophagectomy. METHODS: A systematic search of the literature was performed on September 2, 2022. Screening of titles and abstracts, full-text articles, and evaluation of methodological quality was performed by two authors. Case reports, conference proceedings, and animal studies were excluded. A meta-analysis of peri-operative oral care on the odds of post-operative pneumonia after esophagectomy was performed using Revman 5.4.1 with a Mantel-Haenszel, random-effects model. RESULTS: A total of 736 records underwent title and abstract screening, leading to 28 full-text studies evaluated for eligibility. A total of nine studies met the inclusion criteria and underwent meta-analysis. Meta-analysis revealed a significant reduction in post-operative pneumonia among patients undergoing pre-operative oral care intervention compared to those without an oral care intervention (OR 0.57, 95% CI 0.43-0.74, p < 0.0001; I2 = 49%). CONCLUSION: Pre-operative oral care interventions have significant potential in the reduction of post-operative pneumonia after esophagectomy. North American prospective studies, as well as studies on the cost-benefit analysis, are required.
Assuntos
Esofagectomia , Pneumonia , Animais , Incidência , Esofagectomia/efeitos adversos , Estudos Prospectivos , Pneumonia/epidemiologia , Pneumonia/etiologia , Pneumonia/prevenção & controle , Análise Custo-BenefícioRESUMO
BACKGROUND: Handover to the trauma team is crucial to trauma care. The emergency medical services (EMS) report must be concise, contain key details, and be time-limited. Effective handover is difficult, often occurring between unfamiliar teams, in chaotic environments, and without standardization. We aimed to evaluate handover formats in comparison to ad-lib communication during trauma handover. METHODS: We conducted a single-blind randomized simulation trial evaluating 2 structured handover formats. Paramedics randomly assigned to ad-lib, ISOBAR (identify, situation, observations, background, agreed plan, and readback) or IMIST (identification, mechanism/medical complaint, injuries/ information about complaint, signs, treatments) handover formats underwent scenarios in an ambulance, then transfer to the trauma team. Assessment of handovers was completed by the trauma team and by experts using audiovisual recordings. RESULTS: Twenty-seven simulations were conducted, 9 for each handover format. Participant ratings of the usefulness of the IMIST and ISOBAR formats were 9/10 and 7.5/10, respectively (p = 0.097). Quality of the handover was deemed higher by team members when a statement of objective vital signs and a logical format was used. Handovers delivered with confidence, directed and summarized by a trauma team leader, before physical patient transfer, and without interruption were identified as having the highest quality. The type of format was not a significant contributor to handover; however, we identified a matrix of factors affecting the quality of trauma handover. CONCLUSION: Our study shows agreement by prehospital and hospital personnel that a standardized handover tool is preferred. A brief confirmation of physiologic stability, including vital signs, limiting distractions, and team summarization improves handover effectiveness.