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Metabolic and bariatric surgery (MBS) is the most effective and durable therapeutic intervention for patients with obesity. In recent years, laparoscopic sleeve gastrectomy (SG) has become the most commonly performed primary MBS procedure owing to its technical feasibility and excellent short-term outcomes. Despite these favorable results and perceived advantages, SG is associated with several unique complications. Complications such as a postoperative leak or bleeding have been more commonly observed and reported than others, and their management approaches are well described. However, other complications following SG are far less familiar to surgeons, which may delay recognition and result in poor patient outcomes. Of these complications, we describe splenic injuries; esophageal perforation; staple line malformations; stapling of intraluminal devices; phytobezoar formation; gastro-colic, gastro-pleural and gastro-bronchial fistula; pancreatic leak; and portomesenteric venous thrombosis. It is paramount for surgeons to be aware of these underreported issues and have the resources to learn how to recognize and manage them when they arise. This review aims to describe rare (i.e., reported incidence <1%) and underdescribed complications after SG, focusing on causes, clinical presentation, prevention strategies, and management.
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Histiocytic sarcoma (HS) is a rare neoplasm with no known cause. This sarcoma is characterized by morphology similar to that demonstrated by mature tissue histiocytes and mostly afflicts adults. HSs typically have a poor prognosis due to a rapidly progressive clinical course. Our patient's case was unique due to its presentation four years after completion of treatment for B-cell acute lymphoblastic leukemia. The patient experienced progression with initial therapy for HS. With dual immunotherapy and radiation, however, the patient has remained clinically stable without detectable disease. Immunotherapy may be a successful and tolerable therapeutic option for histiocytic disease.
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Sarcoma Histiocítico , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Sarcoma Histiocítico/terapia , Enfermedades Raras , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , InmunoterapiaRESUMEN
BACKGROUND: The role of metabolic and bariatric surgery (MBS), in synergy with left ventricular assist device (LVAD) implantation, in the scope of end-stage heart failure management for patients with severe obesity is not well elucidated. METHODS: We conducted a meta-analysis using Cochrane, Embase, PubMed, and Scopus databases to include articles from their inception to November 2022. RESULTS: A total of 271 patients who underwent MBS during or after the LVAD implantation were included from eleven separate studies. After surgery, 67.4% of patients were listed on the heart transplant waitlist with 32.5% undergoing a successful transplant. We reported a mean listing time of 13.8 months. Finally, the pooled postoperative complication rate, 30-day readmission rate, and one-year mortality rate were 47.6%, 23.6% and 10.2% respectively. CONCLUSIONS: MBS and LVAD is a safe and effective approach to bridge patients with severe obesity and end-stage heart failure for definitive heart transplantation.
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Cirugía Bariátrica , Insuficiencia Cardíaca , Trasplante de Corazón , Corazón Auxiliar , Obesidad Mórbida , Humanos , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Insuficiencia Cardíaca/cirugía , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
BACKGROUND: Leak is a feared complication of bariatric surgeries. Time to presentation is important in their management. We used the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) to evaluate the rate and timing of leaks. OBJECTIVES: To determine when leaks present after bariatric surgery. SETTING: MBSAQIP database. METHODS: The MBSAQIP Participant Use Files (PUF) for the years 2015-2020 were evaluated. Outcomes of interest were "organ space infection" and "leak." We evaluated the time to presentation for these variables as well as patient characteristics, operative time, complication rates and 30-day outcomes. RESULTS: There were 370,369 sleeve gastrectomies (SG) and 159,280 Roux-en-Y gastric bypasses (RYGB). We identified 598 (.16%) SG leaks with an average time to presentation of 13.2 ± 7.8 days. For RYGB, there were 520 leaks (.32%) with an average time to presentation of 9.5 ± 7.4 days. Both procedures had longer operative times for the patients with leak; RYGB was 115 minutes versus 131 minutes and SG was 67 minutes versus 77 minutes (both P < .01). SG and RYGB patients with a leak had a higher relative risk (RR) of grade 4 and 5 Clavien-Dindo complication rates. RR of mortality rates in SG patients with leak was 35.2 (confidence interval (CI): 20-61) and in RYGB with leak was 31.4 (CI: 19-50). CONCLUSIONS: The length of time for SG leak presentation was more delayed than RYGB leak presentation. Surgeons should be vigilant for leaks for at least 3 weeks after surgery. Leaks increase the mortality rate and overall serious complications.
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Cirugía Bariátrica , Derivación Gástrica , Obesidad Mórbida , Humanos , Obesidad Mórbida/cirugía , Mejoramiento de la Calidad , Resultado del Tratamiento , Estudios Retrospectivos , Gastrectomía , AcreditaciónRESUMEN
Hematologic tumors are mostly treated with chemotherapies that have poor toxicity profiles. While molecular tumor profiling can expand therapeutic options, our understanding of potential targetable drivers comes from studies of adult liquid tumors, which does not necessarily translate to efficacious treatment in pediatric liquid tumors. There is also no consensus on when profiling should be performed and its use in guiding therapies. We describe a single institution's experience in integrating profiling for liquid tumors. Pediatric patients diagnosed with leukemia or lymphoma and who underwent tumor profiling were retrospectively reviewed. Ten (83.3%) patients had relapsed disease prior to tumor profiling. Eleven (91.7%) patients had targetable alterations identified on profiling, and three (25%) received targeted therapy based on these variants. Of the three patients that received targeted therapy, two (66.7%) were living, and one (33.3%) decreased. For a portion of our relapsing and/or treatment-refractory patients, genetic profiling was feasible and useful in tailoring therapy to obtain stable or remission states. Practitioners may hesitate to deviate from the 'standard of therapy', resulting in the underutilization of profiling results. Prospective studies should identify actionable genetic variants found more frequently in pediatric liquid tumors and explore the benefits of proactive tumor profiling prior to the first relapse.
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The application of molecular tumor profiles in clinical decision making remains a challenge. To aid in the interpretation of complex biomarkers, molecular tumor boards (MTBs) have been established worldwide. In the present study, we show that a multidisciplinary approach is essential to the success of MTBs. Our MTB, consisting of pediatric oncologists, pathologists, and pharmacists, evaluated 115 cases diagnosed between March 2016 and September 2021. If targetable mutations were identified, pharmacists aided in the evaluation of treatment options based on drug accessibility. Treatable genetic alterations detected through molecular testing most frequently involved the cell cycle. For 85% of the cases evaluated, our MTB provided treatment recommendations based on the patient's history and results of molecular tumor testing. Only three patients, however, received MTB-recommended targeted therapy, and only one of these patients demonstrated an improved clinical outcome. For the remaining patients, MTB-recommended treatment often was not administered because molecular tumor profiling was not performed until late in the disease course. For the three patients who did receive MTB-recommended therapy, such treatment was not administered until months after diagnosis due to physician preference. Thus, the education of healthcare providers regarding the benefits of targeted therapy may increase acceptance of these novel agents and subsequently improve patient survival.
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INTRODUCTION: Marginal ulcer (MU) is a common complication following Roux-en-Y gastric bypass (RYGB) with an incidence rate of up to 25%. Several studies have evaluated different risk factors associated with MU with inconsistent findings. In this meta-analysis, we aimed to identify the predictors of MU after RYGB. METHODS: A comprehensive literature search of PubMed, Embase, and Web of Science databases was conducted through April 2022. All studies that used a multivariate model to assess risk factors for MU after RYGB were included. Pooled odds ratios (OR) with 95% confidence intervals (CI) for risk factors reported in ≥ 3 studies were obtained within a random-effects model. RESULTS: Fourteen studies with 344,829 patients who underwent RYGB were included. Eleven different risk factors were analyzed. Meta-analysis demonstrated that Helicobacter pylori (HP) infection (OR 4.97 [2.24-10.99]), smoking (OR 2.50 [1.76-3.54]), and diabetes mellitus (OR 1.80 [1.15-2.80]), were significant predictors of MU. Increased age, body mass index, female gender, obstructive sleep apnea, hypertension, and alcohol use were not predictors of MU. There was a trend of an increased risk of MU associated with nonsteroidal anti-inflammatory drugs (OR 2.43 [0.72-8.21]) and a lower risk of MU with proton pump inhibitors use (OR 0.44 [0.11-2.11]). CONCLUSIONS: Smoking cessation, optimizing glycemic control, and eradication of HP infection reduce the risk of MU following RYGB. Recognition of predictors of MU after RYGB will allow physicians to identify high-risk patients, improve surgical outcomes, and reduce the risk of MU.
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Derivación Gástrica , Hipertensión , Obesidad Mórbida , Úlcera Péptica , Humanos , Femenino , Derivación Gástrica/efectos adversos , Úlcera Péptica/etiología , Úlcera Péptica/cirugía , Factores de Riesgo , Inhibidores de la Bomba de Protones , Hipertensión/complicaciones , Obesidad Mórbida/cirugía , Obesidad Mórbida/complicaciones , Estudios RetrospectivosRESUMEN
BACKGROUND: It is thought that the clinical course of actively treated pediatric/adolescent cancer patients diagnosed with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is more severe than experienced by the general pediatric population. We describe the clinical course, risk factors affecting presentation, and management of coronavirus disease 2019 (COVID-19) infection for these patients. METHODS: Patients at a single institution receiving cancer therapy while diagnosed with SARS-CoV-2 between January 2020 and June 2021 were retrospectively reviewed. Data collected included age at SARS-CoV-2 diagnosis, sex, ethno-race, adjusted body mass index, and active therapies. RESULTS: Twenty-nine patients met inclusion criteria, with 16 (55.2%) experiencing symptoms. Twenty-three (79.3%) patients required no institutional support; 10 (34.4%) required hospitalization, of which 80.0% required oxygen, 30.0% required intensive care, and 10.0% required intubation. Three (10.3%) patients developed MIS-C. Obesity increased odds of hospitalization (odds ratio=25.5; P =0.002) and oxygenation (odds ratio=14.88; P =0.012). CONCLUSIONS: Hospitalization and MIS-C rates were significantly higher than, whereas mortality rates and symptom presentations were consistent with, rates in the general pediatric population. Obesity was the only risk factor predictive of clinical severity. Cancer treatment modifications and pre-emptive administration of COVID-19 treatment did not modify clinical course.
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COVID-19 , Neoplasias , Humanos , Niño , Adolescente , SARS-CoV-2 , COVID-19/epidemiología , Prueba de COVID-19 , Estudios Retrospectivos , Tratamiento Farmacológico de COVID-19 , Obesidad/complicaciones , Obesidad/epidemiología , Progresión de la Enfermedad , Neoplasias/diagnóstico , Neoplasias/epidemiología , Neoplasias/terapiaRESUMEN
BACKGROUND: The implications of operative time (OT) have been studied in different surgical specialties, showing a correlation with higher incidence rates of postoperative complications. However, the impact of OT on bariatric surgery complications is not well elucidated. METHODS: A retrospective review of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database between 2015 and 2019 was performed. A total of 358,382 SG patients and 123,357 RYGB patients were included. The median OT was 68 min (10-720) and 113 min (10-640) for the sleeve gastrectomy (SG) group and the Roux-en-Y gastric bypass group, respectively. The groups were subdivided into two subgroups based on OT in comparison to the median time of each group. The subgroups were compared for surgical complications and outcomes. To reduce selection bias and risk of confounders, we performed a propensity score matching (PSM) for 22 variables. RESULTS: In the PSM-matched cohort, 18,915 SG and 6,495 RYGB patients were included in each subgroup. The SG cohort showed higher rates of Clavien-Dindo Class 1, 2, 3a, 4, and 5 complications as well as higher rates of readmission, reoperation, and reintervention in the longer OT group before matching. After PSM, the subgroup with longer times continued to have higher rates of Clavien-Dindo Class 2 complications and higher rates of readmission and reoperation. Similarly, there were higher rates of all Clavien-Dindo class complications as well as readmission, reoperation, and reintervention in the RYGB group with higher OT. After PSM, there were still higher rates of Clavien-Dindo Class 3a complications as well as readmission and reintervention in the RYGB subgroup with prolonged OT. CONCLUSION: In both SG and RYGB, longer OT was associated with increased rates of complications as well as readmission, reoperation, and reintervention. Surgeons should be cognizant of the increased rates of complications when operative times are longer.
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Cirugía Bariátrica , Derivación Gástrica , Obesidad Mórbida , Humanos , Obesidad Mórbida/cirugía , Obesidad Mórbida/complicaciones , Tempo Operativo , Cirugía Bariátrica/efectos adversos , Derivación Gástrica/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Gastrectomía/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Roux-en-Y gastric bypass (RYGB) is a recognized, safe bariatric procedure with minimal complications. Marginal ulceration, however, remains a challenging problem with an incidence of 8-12%. While chronic NSAID use is an established risk factor for ulcer formation, aspirin use itself as a cause for marginal ulceration is still unclear. We aim to compare the rates of marginal ulceration in RYGB with and without aspirin use. METHODS: PubMed, ScienceDirect, Cochrane, Web of Science, and Google Scholar were searched for articles between 2008 and 2021 by two independent reviewers using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). The risk of bias was assessed using Newcastle-Ottawa Scale. Meta-analysis was conducted using a fixed-effect model. RESULTS: From 5324 studies screened, we included 3 studies. Two studies had a low risk of bias, and the other one presented a high risk of bias on the Newcastle-Ottawa Scale. We included 24,770 patients, 1911 with aspirin use and 22,859 without aspirin use. After the meta-analysis, patients who used aspirin had a significantly higher marginal ulceration rate than those who did not (OR = 1.33 [95% CI 1.08 to 1.63], P < .002; I2 = 39%). CONCLUSIONS: Aspirin use is associated with increased rates of marginal ulceration after RYGB.
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Derivación Gástrica , Obesidad Mórbida , Humanos , Derivación Gástrica/efectos adversos , Derivación Gástrica/métodos , Úlcera , Obesidad Mórbida/cirugía , Aspirina/efectos adversos , Factores de Riesgo , Estudios RetrospectivosRESUMEN
BACKGROUND: Obesity is associated with an increased incidence of at least 13 types of cancer. Although bariatric surgery has been associated with a reduced risk of hormonal cancers, data for non-hormonal cancers are scarce. The aim of this study was to evaluate the effect of bariatric surgery on the incidence of non-hormonal cancers. METHODS: Cochrane, Embase, PubMed, Scopus, and Web of Science were searched for articles between 1984 and 2018, following the PRISMA system. Meta-analysis was conducted using a random-effect model with subgroup analysis by procedure and cancer type. RESULTS: From 2526 studies screened, 15 were included. There were a total of 18 583 477 patients, 947 787 in the bariatric group and 17 635 690 in the control group. In comparison to the non-surgical group, the bariatric group had a lower incidence of cancer (OR .65 (95 per cent c.i. 0.53 to 0.80); P < 0.002). In the subgroup analysis, Roux-en-Y gastric bypass and sleeve gastrectomy were associated with decreased risk of developing cancer, while no difference was observed with adjustable gastric banding. When evaluated by cancer type, liver (OR 0.417 (95 per cent c.i. 0.323 to 0.538)), colorectal (OR 0.64 (95 per cent c.i. 0.49 to 0.84)), kidney and urinary tract cancer (OR 0.77 (95 per cent c.i. 0.72 to 0.83)), oesophageal (OR 0.60 (95 per cent c.i. 0.43 to 0.85)), and lung cancer (OR 0.796 (95 per cent c.i. 0.45 to 0.80)) also presented a lower cancer incidence in the bariatric group. CONCLUSION: Bariatric surgery is related to an almost 50 per cent reduction in the risk of non-hormonal cancers.
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Cirugía Bariátrica , Derivación Gástrica , Neoplasias , Obesidad Mórbida , Humanos , Obesidad Mórbida/cirugía , Estudios Retrospectivos , Pérdida de Peso , Cirugía Bariátrica/efectos adversos , Cirugía Bariátrica/métodos , Derivación Gástrica/métodos , Gastrectomía/métodos , Neoplasias/epidemiología , Neoplasias/etiología , Neoplasias/cirugía , Estudios Observacionales como AsuntoRESUMEN
Pleural and tracheal injuries remain significant problems, and an easy to use, effective pleural or tracheal sealant would be a significant advance. The major challenges are requirements for adherence, high strength and elasticity, dynamic durability, appropriate biodegradability, and lack of cell or systemic toxicity. We designed and evaluated two sealant materials comprised respectively of alginate methacrylate and of gelatin methacryloyl, each functionalized by conjugation with dopamine HCl. Both compounds are cross-linked into easily applied as pre-formed hydrogel patches or as in situ hydrogels formed at the wound site utilizing FDA-approved photo-initiators and oxidants. Material testing demonstrates appropriate adhesiveness, tensile strength, burst pressure, and elasticity with no significant cell toxicity in vitro assessments. Air-leak was absent after sealant application to experimentally-induced injuries in ex-vivo rat lung and tracheal models and in ex vivo pig lungs. Sustained repair of experimentally-induced pleural injury was observed for up to one month in vivo rat models and for up to 2 weeks in vivo rat tracheal injury models without obvious air leak or obvious toxicities. The alginate-based sealant worked best in a pre-formed hydrogel patch whereas the gelatin-based sealant worked best in an in situ formed hydrogel at the wound site thus providing two potential approaches. These studies provide a platform for further pre-clinical and potential clinical investigations. STATEMENT OF SIGNIFICANCE: Pneumothorax and pleural effusions resulting from trauma and a range of lung diseases and critical illnesses can result in lung collapse that can be immediately life-threatening or result in chronic leaking (bronchopleural fistula) that is currently difficult to manage. This leads to significantly increased morbidity, mortality, hospital stays, health care costs, and other complications. We have developed sealants originating from alginate and gelatin biomaterials, each functionalized by methacryloylation and by dopamine conjugation to have desired mechanical characteristics for use in pleural and tracheal injuries. The sealants are easily applied, non-cytotoxic, and perform well in vitro and in vivo model systems of lung and tracheal injuries. These initial proof of concept investigations provide a platform for further studies.
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Gelatina , Adhesivos Tisulares , Alginatos , Animales , Materiales Biocompatibles , Hidrogeles , Ratas , PorcinosRESUMEN
A 14-year-old boy was injured from playing football, and subsequently developed worsening abdominal pain. CT of the abdomen and pelvis was concerning for a mass of ascending colon, with free fluid in the pelvis. The patient was emergently taken to the operating room where he was found to have a cecal haematoma. The patient underwent a right hemicolectomy and ileocolostomy and was discharged home just days later without any acute complications. As cecal haematomas are a rare entity, the best approach to management is not well defined. When the diagnosis is uncertain, or if the possibility of full-thickness injury exists, exploratory laparoscopy or laparotomy is the safest approach.
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Enfermedades del Ciego/cirugía , Fútbol Americano/lesiones , Hematoma/cirugía , Dolor Abdominal/cirugía , Adolescente , Enfermedades del Ciego/diagnóstico por imagen , Enfermedades del Ciego/etiología , Colectomía , Hematoma/diagnóstico por imagen , Hematoma/etiología , Humanos , Ileostomía , Masculino , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Eosinophilic esophagitis and Barrett's esophagus are believed to be separate disease processes, with erosive esophagitis leading to Barrett's esophagus. We report a rare case of concurrent diagnoses in a pediatric patient and examine the relevant genetic profiles in the esophagus.
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Liver cancer is the 6th leading cause of cancer related deaths in the US even though it ranks 14th in incidence. More men are diagnosed with liver cancer than women, and the number of projected deaths among men (20,020) is almost double that among women (10,140) in the US. Infections like hepatitis and metabolic conditions like obesity are believed to be major risk factors for the onset of liver cancer. Hepatocellular carcinoma (HCC), the most common type of liver cancer, accounts for 75% of all cases. Chemotherapy has not been effective in treating HCC. Targeted therapies are being used in advanced HCC patients due to a better survival and less side effects when compared to traditional chemotherapy. Therapeutic agents targeting the regulators of growth factor signaling pathways and the mediators of downstream signaling-for example, inhibitors of the tyrosine kinase receptor-are used as targeted molecular therapies. Kinase inhibitors that modulate growth signals, such as sorafenib and lenvatinib, are commonly employed in targeted molecular therapy for HCC patients. This review covers these agents, highlighting modes of action and providing details on clinical trials.
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Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Terapia Molecular Dirigida/métodos , Ensayos Clínicos como Asunto , Humanos , Compuestos de Fenilurea/uso terapéutico , Quinolinas/uso terapéutico , Transducción de Señal , Sorafenib/uso terapéuticoRESUMEN
Current statistics related to cancer incidence and cancer-related death rates clearly show that specific racial/ethnic minorities are more likely to be diagnosed and/or die with cancer. Colorectal cancer (CRC) is one of the leading causes of cancer deaths in the United States and it disproportionately affects the non-Hispanic Black or African American (AA) population. When compared to the non-Hispanic White (nHW) population, incidence and death rates in AAs are 28% and 60% higher, respectively. Hispanics have an overall lower CRC incidence rate than nHWs (Hispanics: 35.5 per 100,000 population; nHWs: 40.2 per 100,000 population), but their incidence continues to rise, unlike nHWs, who are experiencing a decline. This disparity between Hispanics and nHWs is further highlighted in the younger Hispanic population. While the cause of the disparities is associated with CRC-related genetic and environmental factors, the role of specific genes/mutations in each population are still not fully unraveled. However, because CRC is a slowly progressing disease, routine screening and/or early intervention are key to achieving better outcomes in CRC patients and ultimately in closing the disparity gap among different populations. This review discusses the major factors influencing the disparities in CRC and also focuses on factors such as treatment response, family history, and screening that potentially contribute to the racial/ethnic disparities in CRC.
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Neoplasias Colorrectales/etnología , Disparidades en el Estado de Salud , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/mortalidad , Detección Precoz del Cáncer , Hispánicos o Latinos , Humanos , Incidencia , PronósticoRESUMEN
BACKGROUND: Pediatric patients suffering from long gap esophageal defects or injuries are in desperate need of innovative treatment options. Our study demonstrates that two different cell sources can adhere to and proliferate on a retrievable synthetic scaffold. In feasibility testing of translational applicability, these cell seeded scaffolds were implanted into piglets and demonstrated esophageal regeneration. METHODS: Either porcine esophageal epithelial cells or porcine amniotic fluid was obtained and cultured in 3 dimensions on a polyurethane scaffold (Biostage). The amniotic fluid was obtained prior to birth of the piglet and was a source of mesenchymal stem cells (AF-MSC). Scaffolds that had been seeded were implanted into their respective Yucatan mini-swine. The cell seeded scaffolds in the bioreactor were evaluated for cell viability, proliferation, genotypic expression, and metabolism. Feasibility studies with implantation evaluated tissue regeneration and functional recovery of the esophagus. RESULTS: Both cell types seeded onto scaffolds in the bioreactor demonstrated viability, adherence and metabolism over time. The seeded scaffolds demonstrated increased expression of VEGF after 6â¯days in culture. Once implanted, endoscopy 3â¯weeks after surgery revealed an extruded scaffold with newly regenerated tissue. Both cell seeded scaffolds demonstrated epithelial and muscle regeneration and the piglets were able to eat and grow over time. CONCLUSIONS: Autologous esophageal epithelial cells or maternal AF-MSC can be cultured on a 3D scaffold in a bioreactor. These cells maintain viability, proliferation, and adherence over time. Implantation into piglets demonstrated esophageal regeneration with extrusion of the scaffold. This sets the stage for translational application in a neonatal model of esophageal atresia.
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Atresia Esofágica/cirugía , Poliuretanos/uso terapéutico , Ingeniería de Tejidos/métodos , Trasplante Autólogo/métodos , Animales , Modelos Animales de Enfermedad , Células Epiteliales/citología , Esófago/citología , Porcinos , Andamios del TejidoRESUMEN
Due to the high cost and environmental instability of antibodies, there is precedent for developing synthetic molecular recognition agents for use in diagnostic sensors. While these materials typically have lower specificity than antibodies, their cross-reactivity makes them excellent candidates for use in differential sensing routines. In the current work, we design a set of charge-containing poly(N-isopropylacrylamide) (PNIPAM) nanogels for use as differential protein receptors in a turbidimetric sensor array. Specifically, NIPAM was copolymerized with methacrylic acid and modified via carbodiimide coupling to introduce sulfate, guanidinium, secondary amine, or primary amine groups. Modification of the ionizable groups in the network changed the physicochemical and protein binding properties of the nanogels. For high affinity protein-polymer interactions, turbidity of the nanogel solution increased, while for low affinity interactions minimal change in turbidity was observed. Thus, relative turbidity was used as input for multivariate analysis. Turbidimetric assays were performed in two buffers of different pH (i.e., 7.4 and 5.5), but comparable ionic strength, in order to improve differentiation. Using both buffers, it was possible to achieve 100% classification accuracy of eleven model protein biomarkers with as few as two of the nanogel receptors. Additionally, it was possible to detect changes in lysozyme concentration in a simulated tear fluid using the turbidimetric sensor array.