RESUMO
A foregut duplication cyst occurring together with both a congenital cystic pulmonary airway malformation and extralobar pulmonary sequestration is an unusual combination. Prenatal ultrasound, MRI, and postnatal CT are helpful for operative planning. Surgical resection is the definitive management for all three anomalies.
RESUMO
BACKGROUND: Early administration of plasma improves mortality in massively transfused patients, but the thawing process causes delay. Small rural centers have been reluctant to maintain thawed plasma due to waste concerns. Our 254-bed rural Level II trauma center initiated a protocol allowing continuous access to thawed plasma, and we hypothesized its implementation would not increase waste or cost. METHODS: Two units of thawed plasma are continuously maintained in the trauma bay blood refrigerator. After 3 days, these units are replaced with freshly thawed plasma and returned to the blood bank for utilization prior to their 5-day expiration date. The blood bank monitors and rotates the plasma. Only trauma surgeons can use the plasma stored in the trauma bay. Wasted units and cost were measured over a 12-month period and compared with the previous 2 years. RESULTS: The blood bank thawed 1127 units of plasma during the study period assigning 274 to the trauma bay. When compared with previous years, we found a significant increase in waste (p < 0.001) and cost (p = 0.020) after implementing our protocol. It cost approximately US $125/month extra to maintain continuous access to thawed plasma during the study period. DISCUSSION: A protocol to maintain thawed plasma in the trauma bay at a rural Level II trauma center resulted in a miniscule increase in waste and cost when considering the scope of maintaining a trauma center. We think this cost is also minimal when compared with the value of having immediate access to thawed plasma. Constant availability of thawed plasma can be offered at smaller rural centers without a meaningful impact on cost. LEVEL OF EVIDENCE: Economic and Value-based Evaluations, Level III.
Assuntos
Transfusão de Componentes Sanguíneos/métodos , Protocolos Clínicos/normas , Hemorragia/terapia , Plasma , Serviços de Saúde Rural/organização & administração , Centros de Traumatologia/organização & administração , Bancos de Sangue/economia , Bancos de Sangue/organização & administração , Bancos de Sangue/normas , Bancos de Sangue/estatística & dados numéricos , Transfusão de Componentes Sanguíneos/economia , Transfusão de Componentes Sanguíneos/estatística & dados numéricos , Custos e Análise de Custo/estatística & dados numéricos , Implementação de Plano de Saúde/economia , Implementação de Plano de Saúde/estatística & dados numéricos , Hemorragia/etiologia , Humanos , Serviços de Saúde Rural/economia , Serviços de Saúde Rural/normas , Serviços de Saúde Rural/estatística & dados numéricos , Fatores de Tempo , Centros de Traumatologia/economia , Centros de Traumatologia/normas , Centros de Traumatologia/estatística & dados numéricosRESUMO
PURPOSE: The literature about ectopic ureters in anorectal malformations is limited. Repair of an anorectal malformation may require dissection near the normal or abnormal insertion of the ureters. Knowledge of the presence and location of ectopic ureters may prevent intraoperative injury. We aim to describe the incidence and location of ectopic ureters in patients with anorectal malformations and to characterize associated renal anomalies. METHODS: This is an IRB-approved retrospective study of patients with anorectal malformations and ectopic ureters identified in our colorectal database. RESULTS: Of 2283 patients with anorectal malformation, 79 (3.5%) had ectopic ureter(s). Of those, 29% had bilateral ectopic ureters. Nearly all (87%) of bilateral ectopic ureters occurred in females. Ectopic ureters most commonly inserted into the bladder neck (33%), vagina (15%), or urethra (13%). Renal dysfunction was noted in a high proportion of patients. The majority (59%) of ectopic ureters were associated with dysfunction of the ipsilateral kidney. Interestingly, 29% of patients with unilateral ureteral ectopia had an abnormal contralateral kidney. Only 22 patients (28%) had two normal kidneys, and 5 (6%) had documented renal failure with 2 (2.5%) requiring renal transplant. This compares to a transplant rate of 0.6% among anorectal malformation patients without ectopic ureter. CONCLUSIONS: The incidence of ectopic ureter is 3.5% among anorectal malformation patients. Cloaca and recto-bladder neck fistula are the types of anorectal malformation with higher incidence. Ureteral ectopia seems to confer an increased risk of renal failure. Identifying ectopic ureters is important for surgical planning and monitoring renal function vigilantly.
Assuntos
Malformações Anorretais/cirurgia , Ureter/anormalidades , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Rim/anormalidades , Masculino , Estudos RetrospectivosRESUMO
AIM OF THE STUDY: Misdiagnosing a cloaca as a disorder of sex development may lead to inappropriate testing, treatment, and negative emotional consequences to families. We were impressed by the fact that a significant number of patients suffering from a cloaca were referred to us with the diagnosis of a "disorder of sex development" previously referred as "ambiguous genitalia" or "intersex". On re-evaluation, none of them truly had a disorder of sex differentiation. This prompted us to conduct the following retrospective review to try to find the cause of the misdiagnosis and the way to prevent it. METHODS: A retrospective review of our colorectal database was performed to identify the total number of patients with cloacas and the number initially diagnosed as "ambiguous genitalia, intersex"/disorder of sex development. The external appearance of their genitalia and unnecessary testing or treatment received were recorded. MAIN RESULTS: A total of 605 patients with cloacas were identified. Of these, 77 (12.7%) were referred to us with the diagnosis of "ambiguous genitalia" and 13 of them (17%) went on to receive an intervention that was not indicated: karyotyping (10), steroids (3), and ovarian biopsy (1). The karyotype result in all patients was XX. The misdiagnosis was triggered by the external appearance of the perineum, simulating a case of virilization with a hypertrophic clitoris, but was simply prominent labial skin. Careful examination of the perineal structure allowed us to determine that it consisted of folded skin with no evidence of corpora. CONCLUSION: Patients born with a cloaca are at risk for mismanagement from being erroneously labeled as disorders of sex development. The diagnosis of a cloacal anomaly is a clinical one. The practitioner must distinguish between phallus-like clitoral hypertrophy and a normal clitoris with prominent labial skin.
Assuntos
Cloaca/anormalidades , Erros de Diagnóstico/prevenção & controle , Transtornos do Desenvolvimento Sexual , Bases de Dados Factuais , Feminino , Genitália/anormalidades , Humanos , Períneo/anormalidades , Estudos RetrospectivosRESUMO
INTRODUCTION: Distal vaginal atresia is a rare condition and treatment approaches are varied, usually driven by symptoms. METHODS: A retrospective review was performed to identify patients with distal vaginal atresia without anorectal malformation. Data collected included age and symptoms at presentation, type and number of operations, and associated anomalies. RESULTS: Eight patients were identified. Four presented at birth with a hydrocolpos and four presented with hematometrocolpos after 12 years of age. Number of operations per patient ranged from one to seven with an average of three. The vaginal reconstruction was achieved by perineal vaginal mobilization in four patients and abdomino-perineal approach in four patients. One patient, with a proximal vagina approximately 7 cm from the perineum, required partial vaginal replacement with colon. In addition, she had hematometrocolpos with an acute inflammation at the time of reconstruction despite menstrual suppression and drainage which may have contributed to the difficulty in mobilizing the vagina. In five patients, distal vaginal atresia was an isolated anomaly. In the other three cases, associated anomalies included: mild hydronephrosis that improved after hydrocolpos decompression (2), cardiac anomaly (2), and vertebral anomaly (1). CONCLUSION: In this series, a distended upper vagina/uterus was a common presentation and the time of reconstruction was driven by the presence of symptoms. Drainage of the hydrocolpos/hydrometrocolpos with menstrual suppression in post-pubertal patients, followed by further work-up, and planned reconstruction is a good surgical strategy.
Assuntos
Procedimentos de Cirurgia Plástica/métodos , Vagina/cirurgia , Doenças Vaginais/cirurgia , Adolescente , Malformações Anorretais , Criança , Feminino , Hematometra/cirurgia , Humanos , Hidrocolpos/diagnóstico , Hidrocolpos/cirurgia , Lactente , Recém-Nascido , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Sacral nerve stimulation (SNS) is frequently used for constipation and fecal incontinence in the adult literature. The purpose of this study is to perform a systemic review of the literature for SNS for constipation and fecal incontinence in children with emphasis in anorectal malformations. METHODS: Systematic literature review was conducted to include all SNS studies in patients < 19 years of age. Studies were separated into those for (1) constipation, (2) bowel and bladder dysfunction, and (3) anorectal malformations. RESULTS: 28 articles were included in the review: (1) 12 constipation (269 patients) and (2) 16 bowel and bladder dysfunction (441 patients). Some studies overlapped groups, as they included some patients with anorectal malformations (4 articles and 29 patients). Constipation studies included slow transit and retention constipation and showed varying degrees of improvement. For bowel and bladder dysfunction, studies also reported varying degrees of improvement using different measures (number of bowel movements per day, transit times, and soiling improvement). There was no specific description of the results in anorectal malformation (ARM) cases and also information regarding specific ARM type, sacral ratio, or presence of tethered cord. CONCLUSIONS: SNS for constipation and urinary problems seems to be promising. Data are limited and heterogeneous, and SNS cannot be definitively encouraged or discouraged in patients with ARM, based on current studies. Future studies should include more objective measurements of bowel outcomes and specify outcomes related to patients with anorectal malformations including information regarding their specific malformation, sacral ratio, and presence of tethered cord. Complications' rate is considerable high.
Assuntos
Malformações Anorretais/complicações , Constipação Intestinal/terapia , Terapia por Estimulação Elétrica/métodos , Incontinência Fecal/terapia , Sacro/inervação , Criança , Pré-Escolar , Constipação Intestinal/etiologia , Incontinência Fecal/etiologia , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Resident work hour restrictions and required protected didactic time limit their ability to perform clinical duties and participate in structured education. Advanced practice providers (APPs) have previoulsy been shown to positively impact patients' outcomes and overall hospital costs. We describe a model in which nurse practitioners (NPs) improve resident education and American Board of Surgery In Training Examination (ABSITE) scores by providing support to our trauma and acute care surgery (ACS) service thereby protecting resident didactic time. MATERIALS AND METHODS: A new educational model aimed to improve ABSITE scores was created, increasing protected resident didactic time. The addition of three full-time NPs to the ACS service allowed implementation of this redesigned academic curriculum to be put into effect without neglecting patient or service-related responsibilities that were previously fulfilled by resident staff. Resident ABSITE results including standard score, percent correct, and percentile were compared before and after the educational changes were instituted. RESULTS: Eleven residents' scores were included. For each ABSITE score, we used a mixed model with time and postgraduate year (PGY) level as fixed effects and subject ID as a random effect. The interaction term between PGY level and time was not significant and removed from the model. A significant main effect of PGY level and of time was then observed. A statistically significant improvement in ABSITE scores after intervention was observed across all the PGY levels. Standard score increased 77.3 points (P-value = 0.001), percent correct increased 5.9% (P-value = 0.002), and percentile increased 23.8 (P-value = 0.02). Following the educational reform, no residents scored below the 35th percentile. CONCLUSIONS: Utilization of NPs on our ACS service provided adequate service coverage, allowing the implementation of an educational reform increasing protected resident education time and improved ABSITE scores.
Assuntos
Cirurgia Geral/educação , Internato e Residência/métodos , Modelos Educacionais , Profissionais de Enfermagem/organização & administração , Carga de Trabalho/normas , Avaliação Educacional/estatística & dados numéricos , Hospitais de Ensino/organização & administração , Hospitais de Ensino/normas , Humanos , Internato e Residência/normas , Internato e Residência/estatística & dados numéricos , Designação de Pessoal/organização & administração , Estudos Retrospectivos , Fatores de Tempo , Centros de Traumatologia/organização & administração , Centros de Traumatologia/normas , Estados UnidosRESUMO
PURPOSE: Our center has been successfully implementing a bowel management program (BMP) for fecal incontinence consecutive to anorectal malformation and Hirschsprung disease. Recently, the number of patients with spina bifida requiring management for fecal incontinence has increased. The purpose of this study was to review the results of bowel management in patients with spina bifida and the challenges unique to this population. METHODS: A retrospective chart review was performed including all patients with spina bifida who attended our BMP from February 2016 until April 2018. Data collection included: prenatal intervention, gender, age, characteristics of contrast enema, success rateand challenges faced. RESULTS: Twenty-two patients met inclusion criteria 13 of which were females. Three patients had their myelomeningocele repaired prenatally, the remaining were repaired postnatally. Patient ages ranged from 2 to 24 years. Only nine patients were referred to BMP at proper toilet training age. Three patients came to BMP status post an antegrade enema procedure with reported "accidents" on their current regimen. The colon in the contrast enema was non-dilated in all patients and two behaved as hypermotile requiring loperamide. Seventeen patients (77%) were clean of stool and considered successful. Solution leakage during enema administration was the most common challenge and was corrected by increasing the Foley balloon fill volume. CONCLUSIONS: Our bowel management program with enemas is effective for patients with a history of spina bifida. The data support specific considerations for this population including frequent adjustments, close follow-up and specific administration techniques.
Assuntos
Constipação Intestinal/terapia , Incontinência Fecal/terapia , Intestino Neurogênico/terapia , Disrafismo Espinal/complicações , Adolescente , Adulto , Antidiarreicos/uso terapêutico , Criança , Pré-Escolar , Constipação Intestinal/etiologia , Enema , Incontinência Fecal/etiologia , Feminino , Humanos , Loperamida/uso terapêutico , Masculino , Intestino Neurogênico/etiologia , Estudos Retrospectivos , Adulto JovemRESUMO
NEW FINDINGS: What is the central question of this study? Tissue-engineered small intestine was previously generated in vivo by immediate implantation of organoid units derived from both mouse and human donor intestine. Although immediate transplantation of organoid units into patients shows promise as a potential future therapy, some critically ill patients might require delayed transplantation. What is the main finding and its importance? Unlike enteroids, which consist of isolated intestinal crypts, short- and long-term cultured organoid units are composed of epithelial and mesenchymal cells derived from mouse or human intestine. Organoid units do not require added signalling molecules and can generate tissue-engineered intestine in vivo. ABSTRACT: Mouse and human postnatal and fetal organoid units (OUs) maintained in either short-term culture (2 weeks) or long-term culture (from 4 weeks up to 3 months) without adding exogenous growth factors were implanted in immunocompromised mice to form tissue-engineered small intestine (TESI) in vivo. Intestinal epithelial stem and neuronal progenitor cells were maintained in long-term OU cultures from both humans and mice without exogenous growth factors, and these cultures were successfully used to form TESI. This was enhanced with OUs derived from human fetal tissues. Organoid unit culture is different from enteroid culture, which is limited to epithelial cell growth and requires supplementation with R-Spondin, noggin and epidermal growth factor. Organoid units contain multiple cell types, including epithelial, mesenchymal and enteric nervous system cells. Short- and long-term cultured OUs derived from mouse and human intestine develop into TESI in vivo, which contains key components of the small intestine similar to native intestine.
Assuntos
Intestino Delgado/metabolismo , Organoides/metabolismo , Animais , Proliferação de Células/fisiologia , Sistema Nervoso Entérico/metabolismo , Células Epiteliais/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Engenharia Tecidual/métodosRESUMO
OBJECTIVE: This study aims to identify the association, if any, between prehospital scene time, prehospital transport time, and Injury Severity Score (ISS) with in-hospital mortality. METHODS: A retrospective analysis was performed on patients at least 18 years of age who arrived to the hospital alive via emergency medical services (EMS) after a motor vehicle collision (MVC) between 1992 and 2016. These patients were divided into groups based on minutes spent at the scene and in transport. The ISS of the in-hospital mortalities, as well as the entire patient sample for each time frame, was collected. Patients without documented scene time, transport time, or ISS were excluded. RESULTS: Four thousand one hundred ninety-four patients were captured when analyzing scene time, though only 3,980 met inclusion criteria. In addition, 4,177 patients were captured when analyzing transport time, though only 3,979 met inclusion criteria. Scene time and transport time were not statistically significant predictors of in-hospital mortality (P = .31 and P = .458, respectively). ISS was found to be a statistically significant predictor of in-hospital mortality (P < .001). CONCLUSIONS: ISS predicts mortality independent of scene time or transport time for patients who arrive to the hospital alive following an MVC at Guthrie Robert Packer Hospital. Limitations of our study include inability to capture prehospital deaths and inability to correlate ISS with prehospital injury severity scores.
Assuntos
Acidentes de Trânsito/mortalidade , Serviços Médicos de Emergência/estatística & dados numéricos , Mortalidade Hospitalar , Escala de Gravidade do Ferimento , Ferimentos e Lesões/mortalidade , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Veículos Automotores , Estudos Retrospectivos , Fatores de Tempo , Ferimentos não Penetrantes/mortalidade , Ferimentos Penetrantes/mortalidade , Adulto JovemRESUMO
OBJECTIVE: To evaluate whether an educational campaign on distracted driving will have an impact in a given community. METHODS: Investigators were stationed in an employee parking lot of a 256-bed hospital to determine baseline distracted driving followed by a 4-week hospital-wide distracted-driving awareness campaign. The campaign included signs/posters in the hospital, a booth outside of the cafeteria with flyers, a large banner in the employee lot and an opportunity for people to sign a pledge form to drive distraction free. The same employee lot was observed at the same time of the day to re-assess distracted driving immediately following the campaign. The observations were repeated again one year later to evaluate the short and long-term impact of the campaign. RESULTS: A total of 485 vehicles were observed pre-campaign, identifying 170 (35%) distracted drivers at baseline. The awareness campaign resulted in 525 people pledging to drive distraction free. Following the campaign, 495 vehicles were observed and the number of distracted drivers was 64 (12.9%), showing a significant decrease in the number of distracted drivers by 22.1% (p < 0.01). One year later, 530 drivers were observed with 150 (28%) displaying one form of distraction. CONCLUSIONS: A local distracted driving educational campaign resulted in a significant decrease in the number of distracted drivers immediately following the campaign. However, one year after the campaign, there was an increase in distracted driving. The proportion of distracted drivers was still significantly lower than the initial rate of distracted-drivers.
Assuntos
Prevenção de Acidentes/métodos , Acidentes de Trânsito/prevenção & controle , Direção Distraída/prevenção & controle , Promoção da Saúde/métodos , Adulto , Condução de Veículo/estatística & dados numéricos , Conscientização , Telefone Celular , Feminino , Humanos , Masculino , Desempenho Psicomotor , Centros de TraumatologiaRESUMO
We present a case of left upper extremity paresis secondary to acute brachial artery occlusion in an elderly female with active non-ST segment elevation myocardial ischemia (NSTEMI) in the setting of paroxysmal atrial fibrillation. The patient was initially suspected to have a cerebrovascular attack (CVA); however, computed tomography (CT) head was negative for acute stroke. The diagnosis was confirmed by computed tomographic angiography (CTA) of the upper extremity, confirming the diagnosis of acute left brachial artery occlusion. In evaluating a patient with concern for acute stroke with atypical presentation, it is essential to obtain a complete history and perform a rapid and thorough examination. Acute limb ischemia (ALI) should be considered in the differential diagnosis of CVA with atypical presentation.
RESUMO
Pheochromocytomas are rare tumors derived from chromaffin cells located in the adrenal and extra adrenal tissues. Pheochromocytomas are diagnosed biochemically and localized using different imaging modalities. The definitive management is surgical resection. Brown adipose tissues are normally present during fetal development, with regression over time. Brown adipose tissues are thermogenic and usually located in the neck, mediastinum, and retroperitoneum. Here, we report a case of a unilateral pheochromocytoma surrounded by brown fat. The abnormal stimulation of brown fat noted on positive emission tomography scan (PET) resolved after the pheochromocytoma was resected.
RESUMO
The intestine shows extraordinary regenerative potential that might be harnessed to alleviate numerous morbid and lethal human diseases. The intestinal stem cells regenerate the epithelium every 5 days throughout an individual's lifetime. Understanding stem-cell signaling affords power to influence the niche environment for growing intestine. The manifold approaches to tissue engineering may be organized by variations of three basic components required for the transplantation and growth of stem/progenitor cells: (1) cell delivery materials or scaffolds; (2) donor cells including adult stem cells, induced pluripotent stem cells, and in vitro expansion of isolated or cocultured epithelial, smooth muscle, myofibroblasts, or nerve cells; and (3) environmental modulators or biopharmaceuticals. Tissue engineering has been applied to the regeneration of every major region of the gastrointestinal tract from esophagus to colon, with scientists around the world aiming to carry these techniques into human therapy.
Assuntos
Trato Gastrointestinal/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Regeneração , Engenharia Tecidual , Animais , Colo , Esôfago , Humanos , Intestino Delgado , Estômago , Alicerces TeciduaisRESUMO
Liver disease affects large numbers of patients, yet there are limited treatments available to replace absent or ineffective cellular function of this crucial organ. Donor scarcity and the necessity for immunosuppression limit one effective therapy, orthotopic liver transplantation. But in some conditions such as inborn errors of metabolism or transient states of liver insufficiency, patients may be salvaged by providing partial quantities of functional liver tissue. After transplanting multicellular liver organoid units composed of a heterogeneous cellular population that includes adult stem and progenitor cells, both mouse and human tissue-engineered liver (TELi) form in vivo. TELi contains normal liver components such as hepatocytes with albumin expression, CK19-expressing bile ducts and vascular structures with α-smooth muscle actin expression, desmin-expressing stellate cells, and CD31-expressing endothelial cells. At 4 weeks, TELi contains proliferating albumin-expressing cells and identification of ß2-microglobulin-expressing cells demonstrates that the majority of human TELi is composed of transplanted human cells. Human albumin is detected in the host mouse serum, indicating in vivo secretory function. Liquid chromatography/mass spectrometric analysis of mouse serum after debrisoquine administration is followed by a significant increase in the level of the human metabolite, 4-OH-debrisoquine, which supports the metabolic and xenobiotic capability of human TELi in vivo. Implanted TELi grew in a mouse model of inducible liver failure. Stem Cells Translational Medicine 2017;6:238-248.
Assuntos
Células-Tronco Adultas/citologia , Fígado/citologia , Engenharia Tecidual/métodos , Células-Tronco Adultas/metabolismo , Animais , Arginase/metabolismo , Proliferação de Células , Modelos Animais de Doenças , Feminino , Hepatócitos/citologia , Humanos , Fígado/irrigação sanguínea , Camundongos SCID , Organoides/citologiaRESUMO
The cellular and molecular mechanisms that underpin regeneration of the human lung are unknown, and the study of lung repair has been impeded by the necessity for reductionist models that may exclude key components. We hypothesized that multicellular epithelial and mesenchymal cell clusters or lung organoid units (LuOU) could be transplanted to recapitulate proximal and distal cellular structures of the native lung and airways. Transplantation of LuOU resulted in the growth of tissue-engineered lung (TELu) that contained the necessary cell types consistent with native adult lung tissue and demonstrated proliferative cells at 2 and 4 weeks. This technique recapitulated important elements of both mouse and human lungs featuring key components of both the proximal and distal lung regions. When LuOU were generated from whole lung, TELu contained key epithelial and mesenchymal cell types, and the origin of the cells was traced from both ActinGFP and SPCGFP donors to indicate that the cells in TELu were derived from the transplanted LuOU. Alveolar epithelial type 2 cells (AEC2s), club cells, ciliated cells marked by beta-tubulin IV, alveolar epithelial type I cells, Sox-2-positive proximal airway progenitors, p63-positive basal cells, and CGRP-positive pulmonary neuroendocrine cells were identified in the TELu. The mesenchymal components of peribronchial smooth muscle and nerve were identified with a CD31-positive donor endothelial cell contribution to TELu vasculature. TELu successfully grew from postnatal tissues from whole murine and human lung, distal murine lung, as well as murine and human trachea. These data support a model of postnatal lung regeneration containing the diverse cell types present in the entirety of the respiratory tract.
Assuntos
Linhagem da Célula , Proliferação de Células , Pulmão/citologia , Engenharia Tecidual/métodos , Traqueia/metabolismo , Cicatrização , Animais , Células Cultivadas , Humanos , Pulmão/fisiologia , Transplante de Pulmão , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Traqueia/citologiaRESUMO
BACKGROUND: The pediatric intestinal microbiome is impacted by many factors, including age, diet, antibiotics, and environment. We hypothesized that in operative patients, alterations to antibiotics and mechanoluminal stimulation would demonstrate measurable changes in the intestinal microbiome and that microbial diversity would be reduced without normal mechanoluminal stimulation and with prolonged antibiotic treatment. METHODS: Bacterial 16s rRNA was extracted from swabbed samples of 43 intestines from 29 patients, aged 5 days to 13 years old. Swabs were obtained during initial resection or later stoma closure. Samples were compared using phylogenetic diversity whole tree alpha diversity and unweighted UniFrac distance beta diversity and by comparing significantly different taxonomic groups. RESULTS: Microbial community structure varied significantly between obstructive and inflammatory diseases (P = .001), with an effect size of 0.99 (0.97, 1.00). This difference persisted even 6 weeks after return to health. Family Enterobacter and Clostridiaceae predominated in patients with necrotizing enterocolitis or focal intestinal perforation; patients with an obstructive pathology had an abundance of Bacteroides. Comparison of UniFrac distance between paired proximal and distal intestines demonstrated that paired samples were significantly closer than any other comparison. CONCLUSION: In infants, inflammatory and ischemic intestinal pathologies treated with prolonged courses of antibiotics durably alter the intestinal mucosal microbiome. Diversion of mechanoluminal stimulation, however, does not.
Assuntos
Anus Imperfurado/microbiologia , Enterocolite Necrosante/microbiologia , Microbioma Gastrointestinal , Atresia Intestinal/microbiologia , Perfuração Intestinal/microbiologia , Volvo Intestinal/microbiologia , Adolescente , Fatores Etários , Anus Imperfurado/terapia , Criança , Pré-Escolar , Enterocolite Necrosante/terapia , Humanos , Lactente , Recém-Nascido , Atresia Intestinal/terapia , Mucosa Intestinal/microbiologia , Perfuração Intestinal/terapia , Volvo Intestinal/terapiaRESUMO
PURPOSE: Tissue-engineered colon (TEC) might potentially replace absent or injured large intestine, but the enteric nervous system (ENS), a key component, has not been investigated. In various enteric neuropathic diseases in which the TEC is derived from aganglionic donor colon, the resulting construct might also be aganglionic, limiting tissue engineering applications in conditions such as Hirschsprung disease (HD). We hypothesized that TEC might contain a diverse population of enteric neuronal subtypes, and that aganglionic TEC can be populated by neurons and glia when supplemented with ENS progenitor cells in the form of neurospheres. MATERIALS AND METHODS: Human and murine organoid units (OU) and multicellular clusters containing epithelium and mesenchyme were isolated from both mouse and human donor tissues, including from normally innervated and aganglionic colon. The OU were seeded onto a biodegradable scaffold and implanted within a host mouse, resulting in the growth of TEC. Aganglionic murine and human OU were supplemented with cultured neurospheres to populate the absent ENS not provided by the OU to rescue the HD phenotype. RESULTS: TEC demonstrated abundant smooth muscle and clusters of neurons and glia beneath the epithelium and deeper within the mesenchyme. Motor and afferent neuronal subtypes were identified in TEC. Aganglionic OU formed TEC with absent neural elements, but neurons and glia were abundant when aganglionic OU were supplemented with ENS progenitor cells. CONCLUSION: Murine and human TEC contain key components of the ENS that were not previously identified, including glia, neurons, and fundamental neuronal subtypes. TEC derived from aganglionic colon can be populated with neurons and glia when supplemented with neurospheres. Combining tissue engineering and cellular replacement therapies represents a new strategy for treating enteric neuropathies, particularly HD.