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2.
J Pediatr Surg ; 56(10): 1841-1845, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33199059

RESUMO

Minimally invasive repair of pectus excavatum (Nuss procedure) is associated with significant pain, and efforts to control pain impact resource utilization. Bilateral thoracic intercostal nerve cryoablation has been proposed as a novel technique to improve post-operative pain control, though the impact on hospital cost is unknown. METHODS: We conducted a retrospective study of patients undergoing a Nuss procedure from 2016 to 2019. Patients who received cryoablation were compared to those that received traditional pain control (patient-controlled analgesia or epidural). Outcome variables included postoperative opioid usage (milligram morphine equivalents, MME), length of stay (LOS), and hospital cost. RESULTS: Thirty-five of 73 patients studied (48%) received intercostal nerve cryoablation. LOS (1.0 vs 4.0 days, p < 0.01) and total hospital cost ($21,924 versus $23,694, p = 0.04) were decreased in the cryoablation cohort, despite longer operative time (152 vs 74 min, p < 0.01). Cryoablation was associated with decreased opioid usage (15.0 versus 148.6 MME, p < 0.01) during the 24 h following surgery and this persisted over the entire postoperative period, including discharge opioid prescription (112.5 vs 300.0 MME, p < 0.01). CONCLUSION: Bilateral intercostal nerve cryoablation is associated with decreased postoperative opioid usage and decreased resource utilization in pediatric patients undergoing a minimally invasive Nuss procedure for pectus excavatum. LEVEL OF EVIDENCE: Retrospective comparative study, level III.


Assuntos
Criocirurgia , Tórax em Funil , Criança , Tórax em Funil/cirurgia , Custos Hospitalares , Humanos , Nervos Intercostais , Procedimentos Cirúrgicos Minimamente Invasivos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
3.
J Pediatr Surg ; 54(1): 165-169, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30466713

RESUMO

INTRODUCTION: Central venous catheter (CVC) fracture is a common complication. The aim of this study is to examine risk factors resulting in CVC fracture and compare outcomes of children undergoing CVC repair versus replacement. METHODS: A retrospective chart review was conducted from 2000 to 2016 for children with tunneled CVCs. Children with CVC fractures were compared to those without to identify risk factors resulting in fracture. Children with fractured CVCs were divided into repair or replacement treatment groups and outcomes compared. A logistic regression model determined independent predictors of CVC-associated bloodstream infections (CLABSI) after fracture. RESULTS: In the 236 children with CVCs, the fracture rate was 29.2%. Fractured CVCs were more common with double lumen CVC (p = 0.040) and children whose indication was total parenteral nutrition (p = 0.003). Given children often underwent multiple repairs or replacements. 98 CVC repairs and 41 replacements were analyzed. CVC replacements had longer durability than repair (181.98 vs. 98.9 days, p = 0.038). There were no differences in CLABSI incidence for repair vs. replacement (OR 0.5 CI 0.05-4.97) after controlling for other factors. CONCLUSIONS: CVC fracture is a frequent complication in children with tunneled CVCs. CVC repair has no increased incidence of CLABSI but eliminates the intraoperative and anesthetic risks of CVC replacement. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: Level III.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Falha de Equipamento/estatística & dados numéricos , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/etiologia , Criança , Pré-Escolar , Estudos de Coortes , Remoção de Dispositivo , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco
4.
J Pediatr Surg ; 53(6): 1181-1186, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29605268

RESUMO

PURPOSE: Standardized care via a unified surgeon preference card for pediatric appendectomy can result in significant cost reduction. The purpose of this study was to evaluate the impact of cost and outcome feedback to surgeons on value of care in an environment reluctant to adopt a standardized surgeon preference card. METHODS: Prospective observational study comparing operating room (OR) supply costs and patient outcomes for appendectomy in children with 6-month observation periods both before and after intervention. The intervention was real-time feedback of OR supply cost data to individual surgeons via automated dashboards and monthly reports. RESULTS: Two hundred sixteen children underwent laparoscopic appendectomy for non-perforated appendicitis (110 pre-intervention and 106 post-intervention). Median supply cost significantly decreased after intervention: $884 (IQR $705-$1025) to $388 (IQR $182-$776), p<0.001. No significant change was detected in median OR duration (47min [IQR 36-63] to 50min [IQR 38-64], p=0.520) or adverse events (1 [0.9%] to 6 [4.7%], p=0.062). OR supply costs for individual surgeons significantly decreased during the intervention period for 6 of 8 surgeons (87.5%). CONCLUSION: Approaching value measurement with a surgeon-specific (rather than group-wide) approach can reduce OR supply costs while maintaining excellent clinical outcomes. LEVEL OF EVIDENCE: Level II.


Assuntos
Apendicectomia/economia , Apendicite/economia , Análise Custo-Benefício , Custos Hospitalares/estatística & dados numéricos , Qualidade da Assistência à Saúde/economia , Adolescente , Apendicectomia/métodos , Apendicectomia/normas , Apendicite/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Laparoscopia/economia , Masculino , Salas Cirúrgicas/economia , Estudos Prospectivos , Cirurgiões/economia , Tennessee , Resultado do Tratamento
5.
J Pediatr Surg ; 52(10): 1610-1615, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28359587

RESUMO

PURPOSE: Meckel diverticula containing gastric heterotopia predispose to local hyperacidity, mucosal ulceration, and gastrointestinal bleeding in children. Eradication of acid-producing oxyntic cells is performed by either of two surgical methods: segmental enterectomy including the diverticulum or diverticulectomy only. METHODS: Retrospective review of all children having surgical resection of a Meckel diverticulum at a tertiary-referral children's hospital from 2002 to 2016 was performed. Demographic data, surgical method, pathological specimens, and outcomes were evaluated. RESULTS: 102 children underwent surgical resection of a Meckel diverticulum during the study period. 27 (26.5%) children presented with bleeding, of which 16 (59%) had diverticulectomy only, and 11 (41%) had segmental ileal resection. All Meckel diverticula in children presenting with bleeding contained gastric heterotopia, and resection margins were free of gastric mucosa. Histologically, 19 specimens showed microscopic features of ulceration, on average 2.95mm (SD 4.49) from the nearest gastric mucosa (range: 0-16mm). Mean length of hospitalization after ileal resection was 4.0days (SD 1.2) compared to 1.6days (SD 0.9) for diverticulectomy only (p<0.001), with no re-bleeding occurrences. CONCLUSION: In the operative management of children having a bleeding Meckel diverticulum, diverticulectomy-only completely eradicates gastric heterotopia without increased risk of continued bleeding or complications and significantly shortens hospitalization. LEVEL OF EVIDENCE: Treatment Study: Level III.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Hemorragia Gastrointestinal/cirurgia , Divertículo Ileal/cirurgia , Adolescente , Criança , Pré-Escolar , Testes Diagnósticos de Rotina , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Feminino , Mucosa Gástrica , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Divertículo Ileal/complicações , Estudos Retrospectivos , Centros de Atenção Terciária , Resultado do Tratamento
6.
J Trauma Acute Care Surg ; 78(6): 1134-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26151513

RESUMO

PURPOSE: Pediatric trauma patients presenting to referring facilities (RF) often undergo computed tomography (CT) scans to identify injuries before transfer to a Level I pediatric trauma center (PTC). The purpose of our study was to evaluate RF compliance with the American College of Radiology (ACR) guidelines to minimize ionizing radiation exposure in pediatric trauma patients and to determine the frequency of additional or repeat CT imaging after transfer to a PTC. METHODS: After institutional review board approval, a retrospective review of all pediatric trauma admissions from January 2010 to December 2011 at our American College of Surgeons Level I PTC was performed. Patient demographics, means of arrival, Injury Severity Score, and disposition were analyzed. Patients who underwent CT were grouped by means of arrival: those who were transferred from an RF versus those who presented primarily to the PTC. Compliance with ACR guidelines and need for additional or repeat CT scans were assessed for both groups. RESULTS: Six hundred ninety-seven children (aged <18 years) were identified, with a mean age of 10.6 years. Three hundred twenty-one (46%) patients presented primarily to the PTC. Three hundred seventy-six (54%) were transferred from an RF, of which 90 (24%) patients underwent CT imaging before transfer. CT radiation dosing information was available for 79 (88%) of 90 patients. After transfer, 8 (9%) of 90 of children imaged at an RF required additional CT scans. In comparison, 314 (98%) of 321 patients who presented primarily to the PTC and underwent CT received appropriate pediatric radiation dosing. Mean radiation dose at PTC was approximately half of that at RF for CT scans of the head, chest, and abdomen/pelvis (p < 0.01). CONCLUSION: Pediatric trauma patients transferred from RF often undergo CT scanning with higher than recommended radiation doses, potentially placing them at an increased carcinogenic risk. Fortunately, few RF patients required additional CT scans after PTC transfer. Finally, compliance with ACR radiation dose limit guidelines is better achieved at a PTC. LEVEL OF EVIDENCE: Care management study, level IV.


Assuntos
Encaminhamento e Consulta , Tomografia Computadorizada por Raios X , Centros de Traumatologia , Ferimentos e Lesões/diagnóstico por imagem , Criança , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Transferência de Pacientes , Doses de Radiação , Estudos Retrospectivos
7.
Curr Opin Pediatr ; 27(3): 364-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25944307

RESUMO

PURPOSE OF REVIEW: Hirschsprung's disease (HSCR) is characterized by an absence of ganglion cells in the distal hindgut, extending from the rectum to a variable distance proximally, and results from a failure of cranial-caudal neural crest cell migration. Hirschsprung's-associated enterocolitis (HAEC) is a condition with classic manifestations that include abdominal distention, fever and foul-smelling stools, and is a significant and life-threatening complication of HSCR. The purpose of this review was to critically evaluate recent findings regarding the pathophysiology of HAEC. RECENT FINDINGS: Several recent studies have investigated the cause of HAEC in humans and mouse models. These studies suggest that alterations in the intestinal barrier, including goblet cell number and function, and Paneth cell function, impaired gastrointestinal mucosal immunity, including B-lymphocyte trafficking or function and secretory immunoglobulin A production, and dysbiosis of the intestinal microbiota may contribute to the development of HAEC. SUMMARY: Recent studies add to the body of literature, suggesting that the intestinal defects observed in HSCR are not restricted to the aganglionic segment but extend to the mucosal immune system within and beyond the gastrointestinal tract. Future studies further dissecting the mechanisms of HAEC and validating these findings in humans will allow for the development of directed therapeutic interventions.


Assuntos
Enterocolite/fisiopatologia , Doença de Hirschsprung/fisiopatologia , Mucosa Intestinal/fisiopatologia , Intestinos/fisiopatologia , Animais , Criança , Modelos Animais de Doenças , Enterocolite/etiologia , Enterocolite/imunologia , Enterocolite/patologia , Doença de Hirschsprung/complicações , Doença de Hirschsprung/imunologia , Doença de Hirschsprung/patologia , Humanos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Intestinos/microbiologia , Intestinos/patologia , Camundongos , Camundongos Knockout
8.
J Am Coll Surg ; 220(4): 396-402, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25724607

RESUMO

BACKGROUND: The value of routine primary (intraoperative) drain placement after major hepatectomy remains unclear. We sought to determine if primary drainage led to decreased rates of complications, specifically, intra-abdominal biloma or infection requiring a secondary (postoperative) drainage procedure. STUDY DESIGN: All patients who underwent major hepatectomy (≥3 hepatic segments) at 3 institutions, from 2000 to 2012, were identified. Patients with biliary anastomoses were excluded. Primary outcomes were any complication, rate of secondary drainage procedures, bile leak, and 30-day readmission. RESULTS: There were 1,041 patients who underwent major hepatectomy without biliary anastomosis; 564 (54%) had primary drains placed at the surgeon's discretion. Primary drain placement was associated with increased complications (56% vs 44%; p < 0.001), bile leaks (7.3% vs 4.2%; p = 0.048), and 30-day readmissions (16.4% vs 8.0%; p < 0.001), but was not associated with a decrease in secondary drainage procedures (8.0% vs 5.9%; p = 0.23). Patients with primary drains demonstrated higher American Society of Anesthesioloigsts (ASA) class, greater blood loss, more transfusions, and larger resections. After accounting for these significant clinicopathologic variables on multivariate analysis, primary drain placement was not associated with increased risk of any complications. Primary drainage was, however, independently associated with increased risk of bile leak (hazard ratio [HR] 2.04; 95% CI1.02 to 4.09; p = 0.044) and 30-day readmission (HR 1.79; 95% CI1.14 to 2.80; p = 0.011). There still was no reduction in the need for secondary drainage procedures (HR 0.98; p = 0.96). CONCLUSIONS: Primary intraoperative drain placement after major hepatectomy does not decrease the need for secondary drainage procedures and may be associated with increased bile leaks and 30-day readmissions. Routine drain placement is not warranted.


Assuntos
Drenagem/instrumentação , Hepatectomia/métodos , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/cirurgia , Medição de Risco/métodos , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/tendências , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos/epidemiologia
9.
J Surg Res ; 193(2): 523-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25281286

RESUMO

BACKGROUND: In children, severe, life-threatening traumatic injuries of the thoracic aorta can be seen after motor vehicle collisions (MVCs) resulting in a sudden deceleration. Concurrent injuries in the thorax and abdomen can make treatment prioritization difficult and require early recognition and prompt intervention. With the increased utilization of minimally invasive endovascular approaches to traumatic aortic (TA) injuries, patients are often spared the increased surgical morbidity (spinal cord ischemia and renal insults) that can be seen with an open technique. The aim of this study was to evaluate a single American College of Surgeons level 1 pediatric trauma center's 22-y experience with TA injuries in children. METHODS: After the Institutional Review Board approval, a 22-y (January 1990-April 2013) retrospective review of all pediatric trauma patients admitted with TA injuries was performed. Patient demographics including age, injury detail, treatment, and outcomes were recorded for analysis. RESULTS: 17 children (<21-y old) were identified with ages ranging from 13-20 y old. The most common mechanism of injury was MVC with all 17 children sustaining TA injuries. The traumatic injuries included aortic transection (9), intimal flap (5), pseudoaneurysm (2), and contained thoracic rupture (1). All children were managed operatively with those before 2008 using an open technique. The endovascular approach was used in 7/17 (41%) cases with the median length of hospitalization 12 d versus 22.5 d using the open approach (P < 0.05). No child required conversion from an endovascular to an open technique for treatment of the aortic injury. There were no operative deaths, no procedure-related paraplegia and all children were discharged home from the hospital. Two children had mild mental deficits as a result of head trauma. CONCLUSIONS: TA injuries are an uncommon injury in children and can result from MVCs or other sudden deceleration mechanisms. Surgical intervention is required in most of the cases and can be performed safely and effectively with low morbidity using an endovascular approach, which is the evolving approach of choice for thoracic aortic injuries. Lengthy follow-up care is recommended in children treated with an endovascular device to monitor for endoleaks and device complications.


Assuntos
Aorta/lesões , Procedimentos Endovasculares/tendências , Lesões do Sistema Vascular/cirurgia , Ferimentos não Penetrantes/cirurgia , Adolescente , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Lesões do Sistema Vascular/complicações , Lesões do Sistema Vascular/diagnóstico , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/diagnóstico , Adulto Jovem
10.
J Am Coll Surg ; 219(5): 914-22, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25260685

RESUMO

BACKGROUND: Renal insufficiency adversely affects outcomes after cardiac and vascular surgery. The effect of preoperative renal insufficiency on outcomes after major hepatectomy is unknown. STUDY DESIGN: All patients who underwent major hepatectomy (≥3 segments) at 3 institutions from 2000 to 2012 were identified. Resections were performed using low central venous pressure anesthesia. Renal function was analyzed by preoperative serum creatinine (sCr) level. Primary outcomes were major complications (Clavien grade III to V), respiratory failure, renal failure requiring hemodialysis, and 90-day mortality. RESULTS: One thousand one hundred and seventy patients had preoperative sCr levels available. Renal function was analyzed using sCr dichotomized at 1.8 mg/dL, 1 SD higher than the mean value (0.97 ± 0.79 mg/dL) for the cohort. Twenty-two patients had sCr ≥1.8 mg/dL. Major complications occurred in 279 patients (23.8%), respiratory failure in 62 (5.3%), and renal failure in 31 (2.6%). Ninety-day mortality rate was 5.4%. On multivariate analysis, patients with sCr ≥1.8 mg/dL remained at significantly increased risk for major complications (hazard ratio = 3.94; 95% CI, 1.48-10.49; p = 0.006), respiratory failure (hazard ratio = 4.43; 95% CI, 1.33-14.80; p = 0.014), and renal failure (hazard ratio = 4.75; 95% CI, 1.19-18.97; p = 0.028). Serum Cr ≥1.8 mg/dL was not independently associated with 90-day mortality on multivariate analysis (p = 0.27). CONCLUSIONS: Preoperative serum creatinine ≥1.8 mg/dL identifies patients at significantly increased risk of postoperative major complications, respiratory failure, and renal failure requiring dialysis. Patients are well selected for major hepatectomy, and few patients with substantial renal insufficiency are deemed operative candidates.


Assuntos
Hepatectomia , Complicações Pós-Operatórias/etiologia , Insuficiência Renal/complicações , Adulto , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação de Resultados da Assistência ao Paciente , Complicações Pós-Operatórias/mortalidade , Período Pré-Operatório , Insuficiência Renal/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
11.
Am J Physiol Gastrointest Liver Physiol ; 303(5): G610-22, 2012 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22744334

RESUMO

Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that shows promise for the treatment of short bowel syndrome (SBS). Our objective was to investigate how combination GLP-2 + enteral nutrients (EN) affects intestinal adaption in a rat model that mimics severe human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2 (100 µg·kg(-1)·day(-1)), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral reference group. Animals underwent massive distal bowel resection followed by jejunocolic anastomosis and placement of jugular catheters. Starting on postoperative day 4, rats in the EN groups were allowed ad libitum access to EN. Groups provided PN + EN + GLP-2 had their rate of PN reduced by 0.25 ml/day starting on postoperative day 6. Groups provided PN + EN + GLP-2 demonstrated significantly greater body weight gain with similar energy intake and a safe 80% reduction in PN compared with TPN ± GLP-2. Groups provided PN + EN + GLP-2 for 7 or 18 days showed similar body weight gain, residual jejunal length, and digestive capacity. Groups provided PN + EN + GLP-2 showed increased jejunal GLP-2 receptor (GLP-2R), insulin-like growth factor-I (IGF-I), and IGF-binding protein-5 (IGFBP-5) expression. Treatment with TPN + GLP-2 demonstrated increased jejunal expression of epidermal growth factor. Cessation of GLP-2 after 7 days with continued EN sustained the majority of intestinal adaption and significantly increased expression of colonic proglucagon compared with PN + EN + GLP-2 for 18 days, and increased plasma GLP-2 concentrations compared with TPN alone. In summary, EN potentiate the intestinotrophic actions of GLP-2 by improving body weight gain allowing for a safe 80% reduction in PN with increased jejunal expression of GLP-2R, IGF-I, and IGFBP-5 following distal bowel resection in the rat.


Assuntos
Nutrição Enteral , Peptídeo 2 Semelhante ao Glucagon/farmacologia , Intestino Delgado/metabolismo , Síndrome do Intestino Curto/terapia , Animais , Modelos Animais de Doenças , Nutrição Enteral/métodos , Humanos , Fator de Crescimento Insulin-Like I , Masculino , Índice Mitótico , Nutrição Parenteral , Proglucagon/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Síndrome do Intestino Curto/metabolismo
12.
Pediatr Surg Int ; 28(7): 737-40, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22488564

RESUMO

Lipoblastoma is a rare benign neoplasm of embryonic white fatty tissue primarily found in the extremities of children <3 years old (Batanian et al., Cancer Genet Cytogenet 125(1):10-13, 2001; McVay MR et al., J Pediatr Surg 41(6):1067-1071, 2006; Kamal et al., J Pediatr Surg 46(7):E9-E12, 2011). Translocations affecting the 8q11-13 region are commonly reported with lipoblastoma and proper diagnosis requires cytogenetic analysis to distinguish it from malignant myxoid liposarcoma (Miller et al., J Pediatr Surg 32(12):1771-1772, 1997; Morerio et al., Pediatr Blood Cancer 52(1):132-134, 2009). We describe an additional case of lipoblastoma containing a new translocation t(3;8)(p13;q21.1), which has not previously been reported in a healthy asymptomatic child.


Assuntos
Cromossomos Humanos Par 8/genética , Lipoblastoma/diagnóstico , Lipoblastoma/genética , Translocação Genética/genética , Pré-Escolar , Análise Citogenética/métodos , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Lipoblastoma/cirurgia , Imageamento por Ressonância Magnética , Coxa da Perna/diagnóstico por imagem , Coxa da Perna/patologia , Coxa da Perna/cirurgia , Tomografia Computadorizada por Raios X
13.
HPB (Oxford) ; 14(4): 228-35, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22404260

RESUMO

BACKGROUND: The effect of diabetes on survival after resection pancreatic ductal carcinoma (PDAC) is unclear. The present study was undertaken to determine whether pre-operative diabetes has any predictive value for survival. METHODS: A retrospective review from seven centres was performed. Metabolic factors, tumour characteristics and outcomes of patients undergoing resection for PDAC were collected. Univariate and multivariable analyses were performed to determine factors associated with disease-free (DFS) and overall survival (OS). RESULTS: Of the 509 patients in the present study, 31.2% had diabetes. Scoring systems were devised to predict OS and DFS based on a training set (n= 245) and were subsequently tested on an independent set (n= 264). Pre-operative diabetes (P < 0.001), tumour size >2 cm (P= 0.001), metastatic nodal ratio >0.1 (P < 0.001) and R1 margin (P < 0.001) all correlated with DFS and OS on univariate analysis. Scoring systems were devised based on multivariable analysis of the above factors. Diabetes and the metastatic nodal ratio were the most important factors in each system, earning two points for OS and four points for DFS. These scoring systems significantly correlated with both DFS (P < 0.001) and OS (P < 0.001). CONCLUSION: Pre-operative diabetes status provides useful information that can help to stratify patients in terms of predicted post-operative OS and DFS.


Assuntos
Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/cirurgia , Diabetes Mellitus/mortalidade , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Idoso , Carcinoma Ductal Pancreático/secundário , Técnicas de Apoio para a Decisão , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nomogramas , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/patologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Estados Unidos/epidemiologia
14.
Am J Physiol Endocrinol Metab ; 302(7): E885-95, 2012 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-22297302

RESUMO

Phenylketonuria (PKU) is caused by a mutation in the phenylalanine (phe) hydroxylase gene and requires a low-phe diet plus amino acid (AA) formula to prevent cognitive impairment. Glycomacropeptide (GMP) contains minimal phe and provides a palatable alternative to AA formula. Our objective was to compare growth, body composition, and energy balance in Pah(enu2) (PKU) and wild-type mice fed low-phe GMP, low-phe AA, or high-phe casein diets from 3-23 wk of age. The 2 × 2 × 3 design included main effects of genotype, sex, and diet. Fat and lean mass were assessed by dual-energy X-ray absorptiometry, and acute energy balance was assessed by indirect calorimetry. PKU mice showed growth and lean mass similar to wild-type littermates fed the GMP or AA diets; however, they exhibited a 3-15% increase in energy expenditure, as reflected in oxygen consumption, and a 3-30% increase in food intake. The GMP diet significantly reduced energy expenditure, food intake, and plasma phe concentration in PKU mice compared with the casein diet. The high-phe casein diet or the low-phe AA diet induced metabolic stress in PKU mice, as reflected in increased energy expenditure and intake of food and water, increased renal and spleen mass, and elevated plasma cytokine concentrations consistent with systemic inflammation. The low-phe GMP diet significantly attenuated these adverse effects. Moreover, total fat mass, %body fat, and the respiratory exchange ratio (CO(2) produced/O(2) consumed) were significantly lower in PKU mice fed GMP compared with AA diets. In summary, GMP provides a physiological source of low-phe dietary protein that promotes growth and attenuates the metabolic stress induced by a high-phe casein or low-phe AA diet in PKU mice.


Assuntos
Caseínas/farmacologia , Queijo/análise , Fragmentos de Peptídeos/farmacologia , Fenilcetonúrias/tratamento farmacológico , Fenilcetonúrias/metabolismo , Absorciometria de Fóton , Aminoácidos/sangue , Aminoácidos/farmacologia , Animais , Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Citocinas/sangue , Dieta , Dieta com Restrição de Proteínas , Metabolismo Energético/efeitos dos fármacos , Crescimento/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Fenótipo , Fenilcetonúrias/genética , Baço/efeitos dos fármacos , Baço/crescimento & desenvolvimento , Baço/patologia , Esplenomegalia/induzido quimicamente , Esplenomegalia/patologia
15.
Am J Physiol Gastrointest Liver Physiol ; 302(8): G794-804, 2012 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-22281475

RESUMO

Glucagon-like peptide-2 (GLP-2) action is dependent on intestinal expression of IGF-I, and IGF-I action is modulated by IGF binding proteins (IGFBP). Our objective was to evaluate whether the intestinal response to GLP-2 or IGF-I is dependent on expression of IGFBP-3 and -5. Male, adult mice in six treatment groups, three wild-type (WT) and three double IGFBP-3/-5 knockout (KO), received twice daily intraperitoneal injections of GLP-2 (0.5 µg/g body wt), IGF-I (4 µg/g body wt), or PBS (vehicle) for 7 days. IGFBP-3/-5 KO mice showed a phenotype of lower plasma IGF-I concentration, but greater body weight and relative mass of visceral organs, compared with WT mice (P < 0.001). WT mice showed jejunal growth with either IGF-I or GLP-2 treatment. In KO mice, IGF-I did not stimulate jejunal growth, crypt mitosis, sucrase activity, and IGF-I receptor (IGF-IR) expression, suggesting that the intestinotrophic actions of IGF-I are dependent on expression of IGFBP-3 and -5. In KO mice, GLP-2 induced significant increases in jejunal mucosal cellularity, crypt mitosis, villus height, and crypt depth that was associated with increased expression of the ErbB ligand epiregulin and decreased expression of IGF-I and IGF-IR. This suggests that in KO mice, GLP-2 action in jejunal mucosa is independent of the IGF-I system and linked with ErbB ligands. In summary, the intestinotrophic actions of IGF-I, but not GLP-2, in mucosa are dependent on IGFBP-3 and -5. These findings support the role of multiple downstream mediators for the mucosal growth induced by GLP-2.


Assuntos
Peptídeo 2 Semelhante ao Glucagon/farmacologia , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/fisiologia , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/fisiologia , Fator de Crescimento Insulin-Like I/farmacologia , Intestinos/efeitos dos fármacos , Análise de Variância , Animais , Peso Corporal/genética , Peso Corporal/fisiologia , Colo/anatomia & histologia , Colo/efeitos dos fármacos , Colo/crescimento & desenvolvimento , Genes erbB/fisiologia , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/crescimento & desenvolvimento , Intestino Delgado/anatomia & histologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/crescimento & desenvolvimento , Intestinos/anatomia & histologia , Intestinos/crescimento & desenvolvimento , Rim/crescimento & desenvolvimento , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Tamanho do Órgão/genética , Tamanho do Órgão/fisiologia , RNA/biossíntese , RNA/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Baço/crescimento & desenvolvimento
16.
J Gastrointest Surg ; 15(4): 551-7, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21327533

RESUMO

INTRODUCTION: Although patients with pancreatic ductal adenocarcinoma (PDAC) frequently require medications to treat pre-existing conditions, the impact of these treatments on outcomes post-resection is unknown. The purpose of this study was to determine the impact of preoperative medications on overall survival after pancreatic resection. METHODS: Multi-institutional data on preoperative medications and outcomes in patients undergoing resection for PDAC were analyzed. Univariate and multivariate analyses were performed to determine which medications were predictive of early mortality. RESULTS: Of the 518 patients resected for PDAC, 13.3% were being treated preoperatively with insulin, 14.8% were on a statin, 1.7% were on steroids, and 7.6% were on thyroxin. On univariate analysis, patients taking preoperative insulin had a higher 90-day mortality rate relative to those not on insulin (13.0% vs. 4.8%, p = 0.024), and those on a statin had a higher 90-day mortality than those who were not (10.8% vs. 4.6%, p = 0.035). Preoperative steroids and thyroxin were not associated with 90-day mortality (p = 0.409 and p = 0.474, respectively). Insulin and statin use was a stronger predictor of 90-day mortality than history of diabetes (p = 0.101), BMI ≥ 30 (p = 0.166), cardiac disease (p = 0.168), pulmonary disease (p = 1.000), or renal dysfunction (p = 1.000). Older patients also had a higher risk of early postoperative death (p = 0.011). On multivariate analysis, only preoperative insulin usage and statin treatment independently predicted early mortality (odds ratio (OR) = 3.043; 95% confidence interval (CI), 1.256-7.372; p = 0.014, and OR = 2.529; 95% CI, 1.048-6.104; p = 0.039, respectively). Based on the beta coefficients, a simple scoring system was devised to predict survival after resection from preoperative medication use. Zero points were assigned to patients who were on neither insulin nor a statin, one point to those who were on one or the other, and two points to those who were on both insulin and a statin. The score correlated with early postoperative survival (90-day mortality rates of 3.4%, 11.5%, and 13.3% for 0, 1, and 2 points, respectively, p = 0.004). Increasing score was also associated with poorer long-term outcomes, with a median overall survival of 19.6, 15.6, and 11.2 months for 0, 1, and 2 points, respectively (p = 0.002, median follow-up 14.4 months). CONCLUSIONS: Patients with PDAC being treated for pre-existing diabetes or hypercholesterolemia with either insulin or statin-based therapy have an increased risk of early postoperative mortality. A simple scoring system based on preoperative medications can be used to predict early and overall survival following resection.


Assuntos
Carcinoma Ductal Pancreático/mortalidade , Diabetes Mellitus Tipo 1/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Insulina/uso terapêutico , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/cirurgia , Diabetes Mellitus Tipo 1/complicações , Feminino , Humanos , Hipercolesterolemia/complicações , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/cirurgia , Prognóstico
17.
Am J Respir Cell Mol Biol ; 29(4): 432-8, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14500254

RESUMO

Complement is necessary for defense against lung infection with Pseudomonas aeruginosa in mice. We studied in vitro interactions between complement and P. aeruginosa and in vivo effects of complement depletion to better understand this relationship. In vitro, P. aeruginosa strain UI-18 was resistant to killing by mouse serum. However, C3 opsonized the organism (via the alternative and mannose binding lectin [MBL] pathways), and C5 convertase activity on the bacterial surface was demonstrated. In vivo, compared with normal mice, complement-deficient mice experienced higher mortality and failed to sterilize their bronchoalveolar space within 24 h of inoculation. These changes did not seem to be a result of decreased inflammation because complement-deficient mice had normal neutrophil recruitment, greater lung myeloperoxidase content, and, by 24 h, a 35-fold higher level of the CXC chemokine KC. Lung static pressure-volume curves were abnormal in infected animals but were significantly more so in complement deficient mice. These data indicate that although P. aeruginosa is resistant to serum killing, C3 opsonization and C5 convertase assembly occur on its surface. This interaction in vivo plays a central role in host survival beyond just recruitment and activation of phagocytes and may serve to limit the inflammatory response to and tissue injury resulting from bacterial infection.


Assuntos
Quimiocinas CXC , Proteínas do Sistema Complemento/deficiência , Pneumonia Bacteriana/imunologia , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/imunologia , Animais , Quimiocina CXCL1 , Quimiocinas/imunologia , Fatores Quimiotáticos/imunologia , Quimiotaxia de Leucócito/imunologia , Complemento C3/imunologia , Complemento C3/metabolismo , Convertases de Complemento C3-C5/imunologia , Convertases de Complemento C3-C5/metabolismo , Modelos Animais de Doenças , Feminino , Interações Hospedeiro-Parasita/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mortalidade , Peroxidase/imunologia , Pneumonia/imunologia , Pneumonia/metabolismo , Pneumonia Bacteriana/fisiopatologia , Infecções por Pseudomonas/fisiopatologia , Alvéolos Pulmonares/imunologia , Alvéolos Pulmonares/microbiologia , Fenômenos Fisiológicos Respiratórios
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