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1.
J Pediatr Surg ; 52(6): 901-906, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28377023

ABSTRACT

BACKGROUND: Regional anesthesia is commonly used in children. Our hypothesis was that percutaneous ultrasound-guided (PERC) rectus sheath blocks would result in lower postoperative pain scores compared to intraoperative (IO) rectus sheath blocks following umbilical hernia repair. METHODS: A single-institution randomized blinded trial was conducted in pediatric patients undergoing elective umbilical hernia repair. The primary outcome was mean postoperative Wong-Baker pain score. Secondary outcomes included narcotic requirements and length of postoperative stay. RESULTS: Fifty-eight patients were included: 28 PERC and 30 IO. Operating room time was significantly longer in the PERC group (41 vs. 35min, p<0.01). Mean postoperative pain scores (PERC-2.6 vs. IO-3.3, p=0.11), morphine equivalents intraoperatively (PERC-0 vs. IO-0.04mg/kg, p=0.29) and postoperatively (PERC-0.04 vs. IO-0.09mg/kg, p=0.17), time to first postoperative narcotic dose (PERC-30 vs. IO-22min, p=0.33, log-rank test), and postoperative length of stay (PERC-76 vs. IO-80min, p=0.44) were similar. CONCLUSION: Following umbilical hernia repair in children, percutaneous ultrasound-guided and intraoperative rectus sheath blocks resulted in similar mean postoperative pain scores. There were no differences in secondary outcomes such as time to first narcotic, narcotic requirements, and length of stay. The additional resources required to complete a percutaneous ultrasound-guided rectus sheath block may not be warranted. TYPE OF STUDY: Randomized controlled trial. LEVEL OF EVIDENCE: Level I.


Subject(s)
Hernia, Umbilical/surgery , Intraoperative Care/methods , Nerve Block/methods , Pain, Postoperative/prevention & control , Ultrasonography, Interventional , Adolescent , Child , Child, Preschool , Double-Blind Method , Female , Humans , Male , Pain Measurement , Pain, Postoperative/diagnosis , Prospective Studies , Rectus Abdominis/innervation , Treatment Outcome
2.
Pediatr Surg Int ; 33(1): 75-83, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27815641

ABSTRACT

PURPOSE: To review our institutional experience in the surgical treatment of pediatric chronic pancreatitis (CP) and evaluate predictors of long-term pain relief. METHODS: Outcomes of patients ≤21 years surgically treated for CP in a single institution from 1995 to 2014 were evaluated. RESULTS: Twenty patients underwent surgery for CP at a median of 16.6 years (IQR 10.7-20.6 years). The most common etiology was pancreas divisum (n = 7; 35%). Therapeutic endoscopy was the first-line treatment in 17 cases (85%). Surgical procedures included: longitudinal pancreaticojejunostomy (n = 4, 20%), pancreatectomy (n = 9, 45%), total pancreatectomy with islet autotransplantation (n = 2; 10%), sphincteroplasty (n = 2, 10%) and pseudocyst drainage (n = 3, 15%). At a median follow-up of 5.3 years (IQR 4.2-5.3), twelve patients (63.2%) were pain free and five (26.3%) were insulin dependent. In univariate analysis, previous surgical procedure or >5 endoscopic treatments were associated with a lower likelihood of pain relief (OR 0.06; 95% CI 0.006-0.57; OR 0.07; 95%, CI 0.01-0.89). However, these associations were not present in multivariate analysis. CONCLUSION: In children with CP, the step-up practice including a limited trial of endoscopic interventions followed by surgery tailored to anatomical abnormalities and gene mutation status is effective in ensuring long-term pain relief and preserving pancreatic function.


Subject(s)
Pancreas Transplantation/methods , Pancreas/surgery , Pancreatectomy/methods , Pancreaticojejunostomy/methods , Pancreatitis, Chronic/surgery , Practice Guidelines as Topic , Adolescent , Child , Female , Humans , Male , Probability , Transplantation, Autologous , Treatment Outcome , Young Adult
3.
Pediatr Surg Int ; 32(8): 779-88, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27364750

ABSTRACT

PURPOSE: Pancreatic neoplasms are uncommon in children. This study sought to analyze the clinical and pathological features of surgically resected pancreatic tumors in children and discuss management strategies. METHODS: We conducted a retrospective review of patients ≤21 years with pancreatic neoplasms who underwent surgery at a single institution between 1995 and 2015. RESULTS: Nineteen patients were identified with a median age at operation of 16.6 years (IQR 13.5-18.9). The most common histology was solid pseudopapillary neoplasm (SPN) (n = 13), followed by pancreatic neuroendocrine tumor (n = 3), serous cystadenoma (n = 2) and pancreatoblastoma (n = 1). Operative procedures included formal pancreatectomy (n = 17), enucleation (n = 1) and central pancreatectomy (n = 1). SPNs were noninvasive in all but one case with perineural, vascular and lymph node involvement. Seventeen patients (89.5 %) are currently alive and disease free at a median follow-up of 5.7 (IQR 3.7-10.9) years. Two patients died: one with metastatic insulinoma and another with SPN who developed peritoneal carcinomatosis secondary to a concurrent rectal adenocarcinoma. CONCLUSIONS: Pediatric pancreatic tumors are a heterogeneous group of neoplastic lesions for which surgery can be curative. SPN is the most common histology, is characterized by low malignant potential and in selected cases can be safely and effectively treated with a tissue-sparing resection and minimally invasive approach.


Subject(s)
Pancreatectomy/methods , Pancreatic Neoplasms/surgery , Adolescent , Chemotherapy, Adjuvant , Cystadenoma, Serous/diagnosis , Cystadenoma, Serous/mortality , Cystadenoma, Serous/surgery , Female , Humans , Male , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/mortality , Neuroendocrine Tumors/surgery , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/mortality , Retrospective Studies
4.
Ann Thorac Surg ; 101(4): 1338-45, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26794892

ABSTRACT

BACKGROUND: Extensive literature has proved that the Nuss procedure leads to permanent remodeling of the chest wall in pediatric patients with pectus excavatum (PE). However, limited long-term follow-up data are available for adults. Herein, we report a single-institution experience in the management of adult PE with the Nuss procedure, evaluating long-term outcomes and overall patient satisfaction after bar removal. METHODS: Adult patients who underwent PE repair with a modified Nuss procedure between January 1998 and June 2011 were retrospectively identified. Outcomes of interest were postoperative pain, recurrence, and patient satisfaction. A modified single-step Nuss questionnaire was administered to evaluate patient satisfaction and quality-of-life improvement after PE repair. RESULTS: Ninety-eight patients with a median age of 30.9 years (range, 21.8 to 55.1 years) at the time of repair were identified. One bar was placed in most patients (89.7%). Four patients (4.1%) required reoperation for bar displacement. Results after bar removal were overall satisfactory in 94.4% of patients; 2 patients required reoperation for recurrence. Thirty-nine patients participated in the survey. Satisfaction with chest appearance was reported by 89.7% of responders. Seven patients reported dissatisfaction with the overall results; the most common complaints were severe postoperative chest pain and dissatisfaction with surgical scars. CONCLUSIONS: Favorable long-term results can be achieved with the Nuss procedure in adults. However, postoperative pain may require a more aggressive analgesic regimen, and it may be the overriding factor in the patient's perception of the quality of the postoperative course.


Subject(s)
Funnel Chest/surgery , Patient Satisfaction , Adult , Age Factors , Female , Follow-Up Studies , Humans , Male , Middle Aged , Minimally Invasive Surgical Procedures/adverse effects , Postoperative Complications/epidemiology , Recurrence , Reoperation , Retrospective Studies , Time Factors , Treatment Outcome , Young Adult
5.
J Pediatr Surg ; 50(10): 1726-33, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25962841

ABSTRACT

BACKGROUND: Optimal management of recurrent pectus excavatum (PE) has not been established. Here, we review our institutional experience in managing recurrent PE to evaluate long-term outcomes and propose an anatomic classification of recurrences, and a decision-making algorithm. METHODS: Clinical records of patients undergoing repair of recurrent PE (1996-2011) were reviewed. Univariate and multivariate logistic regression analyses were employed to examine patient characteristics as potential predictors for re-recurrence. RESULTS: Eighty-five patients with recurrent PE were identified during the study period. The initial operation was a Ravitch procedure in 85% of cases. Revision procedures were most frequently Nuss repairs (N=73, 86%), with remaining cases managed via open approach. Overall cosmetic and functional results were satisfactory in 67 patients (91.8%) managed with Nuss and in 7 (58%) patients managed with other techniques. Seven (8%) patients required additional surgical revision. Multivariate analysis identified no statistically significant patient or procedural factors predictive of re-recurrence. CONCLUSION: This study demonstrates that the Nuss procedure can be an effective intervention for recurrent pectus excavatum, regardless of the initial repair technique. However, open repair remains valuable when managing severe cases with abnormalities of the sternocostal junction and cartilage regrowth under the sternum.


Subject(s)
Funnel Chest/surgery , Adolescent , Adult , Algorithms , Child , Child, Preschool , Clinical Decision-Making , Female , Humans , Male , Recurrence , Reoperation , Retrospective Studies , Second-Look Surgery , Sternum/surgery , Thoracic Wall/surgery , Young Adult
6.
Ann Thorac Surg ; 99(5): 1835-7, 2015.
Article in English | MEDLINE | ID: mdl-25952229

ABSTRACT

Noonan syndrome is a genetic condition that can present with complex thoracic defects, the management of which often presents a surgical challenge. We present the surgical approach applied to a severe combined excavatum/carinatum deformity that had resulted in a Z-type configuration of the chest in a 9-year-old girl with Noonan syndrome.


Subject(s)
Funnel Chest/etiology , Funnel Chest/surgery , Noonan Syndrome/complications , Pectus Carinatum/etiology , Pectus Carinatum/surgery , Child , Female , Humans
7.
Pediatr Surg Int ; 31(5): 493-9, 2015 May.
Article in English | MEDLINE | ID: mdl-25814003

ABSTRACT

BACKGROUND: Minimally invasive repair of pectus excavatum (MIRPE) is a well-established procedure. However, morbidity rate varies widely among institutions, and the incidence of major complications remains unknown. STUDY DESIGN: The American College of Surgeons 2012 National Surgical Quality Improvement Program-Pediatric (NSQIP-P) participant user file was utilized to identify patients who underwent MIRPE at 50 participant institutions. Outcomes of interest were overall 30-day morbidity, hospital readmission, and reoperation. RESULTS: Chest wall repair designated MIRPE accounted for 0.6% (n = 264) of all surgical cases included in the NSQIP-P database in 2012. The median age at surgical repair was 15.2 years. Thoracoscopy was used in 83.7% of cases. No mediastinal injuries or perioperative blood transfusions were identified. The 30-day readmission rate was 3.8%. Three patients (1.1%) required re-operation due to the following complications: superficial site infection, bar displacement and pneumothorax. The overall morbidity was 3.8% with no incidences of mortality. CONCLUSIONS: This analysis of a large prospective multicenter dataset demonstrates that major complications following MIRPE are uncommon in contemporary practice. Wound infection is the most common complication and the main cause of hospital readmission. Targeted quality improvement initiative should be focused on perioperative strategy to further reduce wound occurrences and hospital readmission.


Subject(s)
Funnel Chest/surgery , Hospitals, Pediatric/statistics & numerical data , Minimally Invasive Surgical Procedures/statistics & numerical data , Plastic Surgery Procedures/statistics & numerical data , Postoperative Complications/epidemiology , Quality Assurance, Health Care/statistics & numerical data , Adolescent , Child , Child, Preschool , Female , Funnel Chest/epidemiology , Humans , Infant , Male , Patient Readmission/statistics & numerical data , Prospective Studies , Reoperation/statistics & numerical data , Retrospective Studies , Societies, Medical , Thoracoscopy , United States/epidemiology
8.
Transplantation ; 99(2): 360-6, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25594552

ABSTRACT

BACKGROUND: Most pediatric kidney transplant recipients eventually require retransplantation, and the most advantageous timing strategy regarding deceased and living donor transplantation in candidates with only 1 living donor remains unclear. METHODS: A patient-oriented Markov decision process model was designed to compare, for a given patient with 1 living donor, living-donor-first followed if necessary by deceased donor retransplantation versus deceased-donor-first followed if necessary by living donor (if still able to donate) or deceased donor (if not) retransplantation. Based on Scientific Registry of Transplant Recipients data, the model was designed to account for waitlist, graft, and patient survival, sensitization, increased risk of graft failure seen during late adolescence, and differential deceased donor waiting times based on pediatric priority allocation policies. Based on national cohort data, the model was also designed to account for aging or disease development, leading to ineligibility of the living donor over time. RESULTS: Given a set of candidate and living donor characteristics, the Markov model provides the expected patient survival over a time horizon of 20 years. For the most highly sensitized patients (panel reactive antibody > 80%), a deceased-donor-first strategy was advantageous, but for all other patients (panel reactive antibody < 80%), a living-donor-first strategy was recommended. CONCLUSIONS: This Markov model illustrates how patients, families, and providers can be provided information and predictions regarding the most advantageous use of deceased donor versus living donor transplantation for pediatric recipients.


Subject(s)
Decision Support Techniques , Donor Selection , Kidney Transplantation/methods , Living Donors/supply & distribution , Adolescent , Adult , Age Factors , Child , Computer Simulation , Eligibility Determination , Female , Graft Survival , HLA Antigens/immunology , Histocompatibility , Humans , Isoantibodies/blood , Kidney Transplantation/adverse effects , Kidney Transplantation/mortality , Male , Markov Chains , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Registries , Reoperation , Risk Factors , Stochastic Processes , Time Factors , Treatment Outcome , United States , Waiting Lists , Young Adult
9.
Pediatr Transplant ; 19(1): 42-7, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25400105

ABSTRACT

The ureteroneocystostomy in kidney transplantation can be performed with a variety of techniques. Over a 20-yr period, we utilized a technique of nipple-valve ureteroneocystostomy for the pediatric kidney transplants performed at our institution. The distal ureter is everted upon itself and anchored in place with four interrupted sutures to create a nipple valve, which is then inserted into the bladder and sewn mucosa-to-mucosa with the same sutures. The muscularis layer is closed around the ureter without tunneling and without routine ureteral stenting. After 109 transplants, patient survival was 97.2, 97.2, and 86.9% at one, five, and 10 yr, respectively. Graft survival was 91.7, 71.7, and 53.9% at one, five, and 10 yr, respectively. The most common cause of graft loss was acute or chronic rejection, seen in 75% of those experiencing graft loss. Two patients (1.8%) developed pyelonephritis in the transplanted kidney. Nipple-valve ureteroneocystostomy in pediatric kidney transplantation is a safe and simple method for performing the ureterovesical anastomosis with a low rate of pyelonephritis after transplantation.


Subject(s)
Cystostomy/methods , Kidney Transplantation/methods , Ureterostomy/methods , Adolescent , Child , Female , Humans , Male
10.
Pediatr Surg Int ; 30(11): 1097-102, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25142797

ABSTRACT

PURPOSE: To examine the association of prehospital criteria with the appropriate level of trauma team activation (TTA) and emergency department (ED) disposition among injured children at a level I pediatric trauma center. METHODS: Injured children younger than 15 years and transported by emergency medical services (EMS) from the scene of injury between January 1, 2008 and December 31, 2011 were identified using the institution's trauma registry. Logistic regression was used to study the main outcomes of interest, full TTA (FTTA) and ED disposition. RESULTS: Out of 3,213 children, 1,991 were eligible and analyzed. Only 279 children initiated the FTTA and 73.9% were admitted. Having a chest injury, abnormal heart rate or Glasgow Coma Scale less than 9 (GCSLT9) in the field was associated with higher odds of initiating the FTTA (odds ratio [OR] = 3.33, 95% confidence interval [CI] 1.54-7.20; OR = 2.59, CI 1.15-5.79 and OR = 2.67, CI 1.14-6.22, respectively). Children with the criteria above in addition to abdominal injury were more likely to be discharged to the ICU, OR or morgue compared to those without them. CONCLUSION: Children with GCSLT9, abnormal heart rate, chest and abdominal injury showed a strong association with FTTA and higher resource utilization.


Subject(s)
Emergency Service, Hospital/statistics & numerical data , Triage/methods , Wounds, Nonpenetrating/diagnosis , Wounds, Nonpenetrating/therapy , Wounds, Penetrating/diagnosis , Wounds, Penetrating/therapy , Academic Medical Centers/statistics & numerical data , Adolescent , Child , Child, Preschool , Female , Glasgow Coma Scale , Humans , Infant , Injury Severity Score , Male , Odds Ratio , Retrospective Studies , Trauma Centers/statistics & numerical data , Triage/statistics & numerical data
11.
J Pediatr Surg ; 49(4): 575-82, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24726116

ABSTRACT

BACKGROUND: The safety and efficacy of minimally invasive pectus excavatum repair have been demonstrated over the last twenty years. However, technical details and perioperative management strategies continue to be debated. The aim of the present study is to review a large single-institution experience with the modified Nuss procedure. METHODS: A retrospective review was performed of patients who underwent primary pectus excavatum repair at a single tertiary hospital via a modified Nuss procedure that included: no thoracoscopy, retrosternal dissection achieved via a left-to-right thoracic approach, four-point stabilization of the bar, and no routine epidural analgesia. Data collected included demographics, preoperative symptoms, operative characteristics, hospital charges and postoperative outcomes. RESULTS: A total of 336 pediatric patients were identified. No cardiac perforations occurred and the rate of pericarditis was 0.6%. Contemporary rates of bar displacement have fallen to 1.2%. Routine use of chlorhexidine scrub reduced superficial site infections to 0.7%. Two patients (0.6%) with severe recurrence required reoperation. Bars were removed after an average period of 31.7(SD 13.2) months, with satisfactory cosmetic and functional results in 94.9% of cases. CONCLUSIONS: We report here a single-institution large volume experience, including modifications to the Nuss procedure that make the technique simpler and safer, improve results, and minimize hospital charges.


Subject(s)
Funnel Chest/surgery , Minimally Invasive Surgical Procedures/methods , Orthopedic Procedures/methods , Perioperative Care/methods , Adolescent , Baltimore , Female , Funnel Chest/economics , Hospital Charges/statistics & numerical data , Hospitals, High-Volume , Humans , Internal Fixators , Male , Minimally Invasive Surgical Procedures/economics , Minimally Invasive Surgical Procedures/instrumentation , Orthopedic Procedures/economics , Orthopedic Procedures/instrumentation , Perioperative Care/economics , Postoperative Complications/economics , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Reoperation/statistics & numerical data , Retrospective Studies , Treatment Outcome
12.
Pediatrics ; 133(4): 594-601, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24616363

ABSTRACT

OBJECTIVE: To investigate changes in pediatric kidney transplant outcomes over time and potential variations in these changes between the early and late posttransplant periods and across subgroups based on recipient, donor, and transplant characteristics. METHODS: Using multiple logistic regression and multivariable Cox models, graft and patient outcomes were analyzed in 17,446 pediatric kidney-only transplants performed in the United States between 1987 and 2012. RESULTS: Ten-year patient and graft survival rates were 90.5% and 60.2%, respectively, after transplantation in 2001, compared with 77.6% and 46.8% after transplantation in 1987. Primary nonfunction and delayed graft function occurred in 3.3% and 5.3%, respectively, of transplants performed in 2011, compared with 15.4% and 19.7% of those performed in 1987. Adjusted for recipient, donor, and transplant characteristics, these improvements corresponded to a 5% decreased hazard of graft loss, 5% decreased hazard of death, 10% decreased odds of primary nonfunction, and 5% decreased odds of delayed graft function with each more recent year of transplantation. Graft survival improvements were lower in adolescent and female recipients, those receiving pretransplant dialysis, and those with focal segmental glomerulosclerosis. Patient survival improvements were higher in those with elevated peak panel reactive antibody. Both patient and graft survival improvements were most pronounced in the first posttransplant year. CONCLUSIONS: Outcomes after pediatric kidney transplantation have improved dramatically over time for all recipient subgroups, especially for highly sensitized recipients. Most improvement in graft and patient survival has come in the first year after transplantation, highlighting the need for continued progress in long-term outcomes.


Subject(s)
Kidney Transplantation/trends , Adolescent , Child , Child, Preschool , Female , Graft Survival , Humans , Infant , Kidney Transplantation/mortality , Male , Survival Rate , Time Factors , Treatment Outcome , United States
13.
J Pediatr Surg ; 49(1): 55-60; discussion 60, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24439581

ABSTRACT

BACKGROUND: Acquired Jeune's syndrome is a severe iatrogenic deformity of the thoracic wall following a premature and aggressive open pectus excavatum repair. We report herein our technique and experience with this rare condition. METHODS: From 1996 to 2011, nineteen patients with acquired Jeune's syndrome were retrospectively identified in a tertiary referral center. The technique used to expand and reconstruct the thoracic wall consisted of 1) release of the sternum from fibrous scar tissue, 2) multiple osteotomies along the lateral aspect of the ribs with anterior advancement of costal-cartilages to protect the heart, 3) stabilization of the thorax by placing a curved bar for retrosternal support and, 4) restoration of the sterno-costal junction by wiring the lower cartilages to the edge of the sternum. RESULTS: Major complications observed in this series were: bar displacement (seven cases), postoperative death from cardiac arrest following bronchoscopy (one case), late cardiac tamponade from migration of wire suture fragment (one case), and need for multiple reoperations (one case). Long-term cosmetic results and improvement in daily quality of life were reported as positive in the majority of cases. CONCLUSIONS: Anterior chest wall reconstruction successfully treated our series of patients with acquired Jeune's syndrome. This multifaceted technique is an effective procedure that allows expansion of the thoracic cavity and improvement of aerobic activity.


Subject(s)
Osteotomy/methods , Plastic Surgery Procedures , Postoperative Complications/surgery , Thoracic Wall/surgery , Bone Wires , Bronchoscopy/adverse effects , Child , Child, Preschool , Equipment Failure , Esthetics , Female , Foreign-Body Migration , Funnel Chest/surgery , Humans , Infant , Internal Fixators , Male , Preoperative Care , Quality of Life , Radiography , Reoperation , Retrospective Studies , Sternum/surgery , Syndrome , Thoracic Wall/diagnostic imaging , Thoracic Wall/injuries , Thoracic Wall/pathology
14.
J Pediatr Surg ; 49(1): 61-5; discussion 65, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24439582

ABSTRACT

PURPOSE: The lungs of infants born with congenital diaphragmatic hernia suffer from immaturity as well as the short and long term consequences of ventilator-induced lung injury, including chronic lung disease. Antenatal and postnatal steroids are among current strategies promoted to treat premature lungs and limit long term morbidity. Although studied in whole-animal models, insight into ventilator-induced injury at the alveolar-capillary interface as well as the benefits of steroids, remains limited. The present study utilizes a multi-fluidic in vitro model of the alveolar-interface to analyze membrane disruption from compressive aerodynamic forces in dexamethasone-treated cultures. METHODS: Human alveolar epithelial cell lines, H441 and A549, were cultured in a custom-built chamber under constant aerodynamic shear followed by introduction of pressure stimuli with and without dexamethasone (0.1µM). On-chip bioelectrical measurements were noted to track changes to the cellular surface and live-dead assay to ascertain cellular viability. RESULTS: Pressure-exposed alveolar cultures demonstrated a significant drop in TEER that was less prominent with an underlying extracellular-matrix coating. Addition of dexamethasone resulted in increased alveolar layer integrity demonstrated by higher TEER values. Furthermore, dexamethasone-treated cells exhibited faster recovery, and the effects of pressure appeared to be mitigated in both cell types. CONCLUSION: Using a novel in vitro model of the alveolus, we demonstrate a dose-response relationship between pressure application and loss of alveolar layer integrity. This effect appears to be alleviated by dexamethasone and matrix sub-coating.


Subject(s)
Barotrauma/prevention & control , Dexamethasone/pharmacology , Pulmonary Alveoli/drug effects , Ventilator-Induced Lung Injury/prevention & control , Air , Air Pressure , Basement Membrane/drug effects , Cell Culture Techniques/instrumentation , Cell Line , Cell Membrane/drug effects , Cell Survival , Collagen , Dexamethasone/administration & dosage , Dose-Response Relationship, Drug , Drug Combinations , Drug Evaluation, Preclinical , Epithelial Cells/cytology , Epithelial Cells/drug effects , Humans , Laminin , Proteoglycans , Pulmonary Alveoli/cytology , Rheology/instrumentation , Surface Properties
15.
J Immunol ; 192(4): 1806-14, 2014 Feb 15.
Article in English | MEDLINE | ID: mdl-24403532

ABSTRACT

Sepsis is a major cause of mortality, and dysregulation of the immune response plays a central role in this syndrome. H2S, a recently discovered gaso-transmitter, is endogenously generated by many cell types, regulating a number of physiologic processes and pathophysiologic conditions. We report that H2S increased survival after experimental sepsis induced by cecal ligation and puncture (CLP) in mice. Exogenous H2S decreased the systemic inflammatory response, reduced apoptosis in the spleen, and accelerated bacterial eradication. We found that C/EBP homologous protein 10 (CHOP), a mediator of the endoplasmic reticulum stress response, was elevated in several organs after CLP, and its expression was inhibited by H2S treatment. Using CHOP-knockout (KO) mice, we demonstrated for the first time, to our knowledge, that genetic deletion of Chop increased survival after LPS injection or CLP. CHOP-KO mice displayed diminished splenic caspase-3 activation and apoptosis, decreased cytokine production, and augmented bacterial clearance. Furthermore, septic CHOP-KO mice treated with H2S showed no additive survival benefit compared with septic CHOP-KO mice. Finally, we showed that H2S inhibited CHOP expression in macrophages by a mechanism involving Nrf2 activation. In conclusion, our findings show a protective effect of H2S treatment afforded, at least partially, by inhibition of CHOP expression. The data reveal a major negative role for the transcription factor CHOP in overall survival during sepsis and suggest a new target for clinical intervention, as well potential strategies for treatment.


Subject(s)
Bacteria/immunology , Hydrogen Sulfide/metabolism , Sepsis/metabolism , Transcription Factor CHOP/antagonists & inhibitors , Animals , Apoptosis/drug effects , Caspase 3/metabolism , Cecum/surgery , Cytokines/biosynthesis , Endoplasmic Reticulum Stress/drug effects , Enzyme Activation , Lipopolysaccharides , Macrophages/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , NF-E2-Related Factor 2/metabolism , Sepsis/drug therapy , Spleen/drug effects , Survival , Transcription Factor CHOP/biosynthesis , Transcription Factor CHOP/genetics
16.
J Am Coll Surg ; 217(6): 1080-9, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24246622

ABSTRACT

BACKGROUND: A multicenter study of pectus excavatum was described previously. This report presents our final results. STUDY DESIGN: Patients treated surgically at 11 centers were followed prospectively. Each underwent a preoperative evaluation with CT scan, pulmonary function tests, and body image survey. Data were collected about associated conditions, complications, and perioperative pain. One year after treatment, patients underwent repeat chest CT scan, pulmonary function tests, and body image survey. A subset of 50 underwent exercise pulmonary function testing. RESULTS: Of 327 patients, 284 underwent Nuss procedure and 43 underwent open procedure without mortality. Of 182 patients with complete follow-up (56%), 18% had late complications, similarly distributed, including substernal bar displacement in 7% and wound infection in 2%. Mean initial CT scan index of 4.4 improved to 3.0 post operation (severe >3.2, normal = 2.5). Computed tomography index improved at the deepest point (xiphoid) and also upper and middle sternum. Pulmonary function tests improved (forced vital capacity from 88% to 93%, forced expiratory volume in 1 second from 87% to 90%, and total lung capacity from 94% to 100% of predicted (p < 0.001 for each). VO2 max during peak exercise increased by 10.1% (p = 0.015) and O2 pulse by 19% (p = 0.007) in 20 subjects who completed both pre- and postoperative exercise tests. CONCLUSIONS: There is significant improvement in lung function at rest and in VO2 max and O2 pulse after surgical correction of pectus excavatum, with CT index >3.2. Operative correction significantly reduces CT index and markedly improves the shape of the entire chest, and can be performed safely in a variety of centers.


Subject(s)
Funnel Chest/surgery , Orthopedic Procedures , Adolescent , Body Image , Child , Exercise Test , Female , Follow-Up Studies , Funnel Chest/diagnostic imaging , Funnel Chest/physiopathology , Funnel Chest/psychology , Humans , Male , Postoperative Complications/epidemiology , Prospective Studies , Psychological Tests , Respiratory Function Tests , Tomography, X-Ray Computed , Treatment Outcome
17.
JAMA Surg ; 148(12): 1123-30, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24173244

ABSTRACT

IMPORTANCE: No national standardized guidelines exist to date for venous thromboembolism (VTE) prophylaxis after pediatric trauma. While the risk of VTE after trauma is generally lower for children than for adults, the precise age at which the risk of VTE increases is not clear. OBJECTIVE: To identify the age at which the risk of VTE after trauma increases from the low rate seen in children toward the higher rate seen in adults. DESIGN, SETTING, AND PARTICIPANTS: Multivariable logistic regression models were used to estimate the association between age and the odds of VTE when adjusting for other VTE risk factors. Participants included 402 329 patients 21 years or younger who were admitted following traumatic injury between January 1, 2008, and December 31, 2010, at US trauma centers participating in the National Trauma Data Bank. MAIN OUTCOMES AND MEASURES: Diagnosis of VTE as a complication during hospital admission. RESULTS: Venous thromboembolism was diagnosed in 1655 patients (0.4%). Those having VTE were more severely injured compared with those not having VTE and more frequently required critical care, blood transfusion, central line placement, mechanical ventilation, and surgery. The risk of VTE was low among younger patients, occurring in 0.1% of patients 12 years or younger, but increased to 0.3% in patients aged 13 to 15 years and to 0.8% in patients 16 years or older. These findings remained when adjusting for other factors, with patients aged 13 to 15 years (adjusted odds ratio, 1.96, 95% CI 1.53-2.52; P < .001) and patients aged 16 to 21 years (adjusted odds ratio, 3.77; 95% CI, 3.00-4.75; P < .001) having a significantly higher odds of being diagnosed as having VTE compared with patients aged 0 to 12 years. These findings were consistent across the level of injury severity and the type of trauma center. CONCLUSIONS AND RELEVANCE: The risk of VTE varies considerably across patient age and increases most dramatically at age 16 years, after a smaller increase at age 13 years. These findings can be used to guide future research into the development of standardized guidelines for VTE prophylaxis after pediatric trauma.


Subject(s)
Venous Thromboembolism/diagnosis , Venous Thromboembolism/epidemiology , Wounds and Injuries/complications , Wounds and Injuries/therapy , Adolescent , Age Factors , Child , Child, Preschool , Cohort Studies , Confidence Intervals , Databases, Factual , Female , Hospitalization/statistics & numerical data , Humans , Incidence , Infant , Male , Odds Ratio , Prognosis , Retrospective Studies , Risk Assessment , Trauma Centers/organization & administration , Trauma Severity Indices , Treatment Outcome , United States , Venous Thromboembolism/etiology , Wounds and Injuries/diagnosis , Young Adult
18.
J Pediatr Surg ; 48(11): 2256-60, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24210196

ABSTRACT

BACKGROUND/PURPOSE: Cloacal exstrophy (CE) is a severe multi-system congenital defect. While spina bifida is a defining feature of cloacal exstrophy, patients are not routinely screened for intracranial anomalies (ICAs). We sought to better characterize this risk of ICA in the CE patient. METHODS: We retrospectively reviewed the medical records of 81 children with CE treated at our institution, identifying intracranial pathology, including hydrocephalus, Chiari malformation and craniosynostosis. Data points included ICA, neural tube defect, surgical procedures, and ambulatory status. RESULTS: Of the 39 patients with cranial imaging, 31% had an ICA: 6 hydrocephalus, 3 Chiari malformation, 1 craniosynostosis, 1 hydrocephalus and craniosynostosis, and 1 Chiari malformation and craniosynostosis. All patients with ICAs had spina bifida. Patients with ICAs underwent more neurosurgical procedures, including more spinal procedures. Patients with ICAs were much more likely to be wheelchair-bound or ambulate minimally when compared to patients without anomalies. CONCLUSION: In our population of CE patients with available head imaging, 31% had an ICA, thus screening would seem prudent. As all patients with ICAs had spina bifida, it may be less important to screen those rare CE patients without spinal pathology. Patients with ICAs were more likely to be wheelchair-bound, suggesting worse neurologic outcomes.


Subject(s)
Abdominal Wall/abnormalities , Abnormalities, Multiple/diagnosis , Cloaca/abnormalities , Neonatal Screening , Neuroimaging , Abdominal Wall/embryology , Abnormalities, Multiple/embryology , Abnormalities, Multiple/surgery , Arnold-Chiari Malformation/epidemiology , Arnold-Chiari Malformation/surgery , Bladder Exstrophy/epidemiology , Bladder Exstrophy/surgery , Counseling , Craniosynostoses/epidemiology , Craniosynostoses/surgery , Decompression, Surgical , Early Diagnosis , Female , Humans , Hydrocephalus/congenital , Hydrocephalus/epidemiology , Hydrocephalus/surgery , Infant, Newborn , Male , Mobility Limitation , Neural Tube Defects/epidemiology , Neural Tube Defects/surgery , Neuroimaging/statistics & numerical data , Neurosurgical Procedures/statistics & numerical data , Prenatal Diagnosis , Prognosis , Retrospective Studies , Spinal Dysraphism/epidemiology , Wheelchairs/statistics & numerical data
20.
Transplantation ; 96(5): 487-93, 2013 Sep 15.
Article in English | MEDLINE | ID: mdl-24002689

ABSTRACT

BACKGROUND: Living-donor kidney transplantation (KT) is encouraged for children with end-stage renal disease due to superior long-term graft survival compared with deceased-donor KT. Despite this, there has been a steady decrease in the use of living-donor KT for pediatric recipients. Due to their young age at transplantation, most pediatric recipients eventually require retransplantation, and the optimal order of donor type is not clear. METHODS: Using the Scientific Registry of Transplant Recipients, we analyzed first and second graft survival among 14,799 pediatric (<18 years old) recipients undergoing KT between 1987 and 2010. RESULTS: Living-donor grafts had longer survival compared with deceased-donor grafts, similarly among both first (adjusted hazard ratio [aHR], 0.78; 95% confidence interval [CI], 0.73-0.84; P<0.001) and second (aHR, 0.74; 95% CI, 0.64-0.84; P<0.001) transplants. Living-donor second grafts had longer survival compared with deceased-donor second grafts, similarly after living-donor (aHR, 0.68; 95% CI, 0.56-0.83; P<0.001) and deceased-donor (aHR, 0.77; 95% CI, 0.63-0.95; P=0.02) first transplants. Cumulative graft life of two transplants was similar regardless of the order of deceased-donor and living-donor transplantation. CONCLUSIONS: Deceased-donor KT in pediatric recipients followed by living-donor retransplantation does not negatively impact the living-donor graft survival advantage and provides similar cumulative graft life compared with living-donor KT followed by deceased-donor retransplantation. Clinical decision-making for pediatric patients with healthy, willing living donors should consider these findings in addition to the risk of sensitization, aging of the living donor, and deceased-donor waiting times.


Subject(s)
Kidney Transplantation , Tissue Donors , Adolescent , Child , Child, Preschool , Female , Graft Survival , Humans , Living Donors , Male , Reoperation
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