Microdeformational wound therapy: A novel option to salvage complex wounds associated with the Nuss procedure.

BACKGROUND: Complex wounds associated with the Nuss procedure are a resource intensive complication that may lead to significant morbidity with potential removal of the implanted device and abandonment of the repair. We report our management technique of this complication utilizing microdeformational wound therapy (MDWT) that is safe, is efficacious and allows for salvage of the repair. OPERATIVE TECHNIQUE: We defined a complex wound as a wound that became suppurative and drained in the postoperative period and failed to resolve with a trial of conventional wound management and antibiotics. Upon recognition of a complex wound, we recommend an initial operative wound debridement. This allows wound cultures, wound assessment and precise initiation of MDWT. It is not uncommon to have exposed hardware in the wound early in the course of therapy. Metal allergy must be excluded. The patient is transitioned to oral antibiotics following resolution of the acute process. MDWT is performed until the wounds are completely epithelialized with no clinical signs of drainage or infection. The average length of MDWT in our patients was 39 days. Following complete wound healing the patients are maintained on antibiotics until implant removal. CONCLUSIONS: The use of microdeformational wound therapy in complex wounds associated with the Nuss procedure is a safe and effective modality. The technique may reduce the likelihood of implant removal with potential recurrent pectus excavatum. TYPE OF STUDY: Operative technique. LEVEL OF EVIDENCE: Level IV, case series with no comparison group.

Percutaneous ultrasound-guided vs. intraoperative rectus sheath block for pediatric umbilical hernia repair: A randomized clinical trial.

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.

How We Manage Pediatric Deep Venous Thrombosis.

Over the past two decades, the incidence and recognition of venous thromboembolism (VTE) in children has significantly increased, likely as a result of improvements in the medical care of critically ill patients and increased awareness of thrombotic complications among medical providers. Current recommendations for the management of VTE in children are largely based on data from pediatric registries and observational studies, or extrapolated from adult data. The scarcity of high-quality evidence-based recommendations has resulted in marked variations in the management of pediatric VTE among providers. The purpose of this article is to summarize our institutional approach for the management of VTE in children based on available evidence, guidelines, and clinical practice considerations. Therapeutic strategies reviewed in this article include the use of conventional anticoagulants, parenteral targeted anticoagulants, new direct oral anticoagulants, thrombolysis, and mechanical approaches for the management of pediatric VTE.

The impact of surgical strategies on outcomes for pediatric chronic pancreatitis.

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.

Laparoscopic versus open inguinal hernia repair in children ≤3: a randomized controlled trial.

PURPOSE: Laparoscopy is being increasingly applied to pediatric inguinal hernia repair. In younger children, however, open repair remains preferred due to concerns related to anesthesia and technical challenges. We sought to assess outcomes after laparoscopic and open inguinal hernia repair in children less than or equal to 3 years. METHODS: A prospective, single-blind, parallel group randomized controlled trial was conducted at three clinical sites. Children ≤3 years of age with reducible unilateral or bilateral inguinal hernias were randomized to laparoscopic herniorrhaphy (LH) or open herniorrhaphy (OH). The primary outcome was the number of acetaminophen doses. Secondary outcomes included operative time, complications, and parent/caregiver satisfaction scores. RESULTS: Forty-one patients were randomized to unilateral OH (n = 10), unilateral LH (n = 17), bilateral OH (n = 5) and bilateral LH (n = 9). Acetaminophen doses, LOS, complications, and parent/caregiver scores did not differ among groups. Laparoscopic unilateral hernia repair demonstrated shorter operative time, a consistent finding for overall laparoscopic repair in univariate (p = 0.003) and multivariate (p = 0.010) analysis. No cases of testicular atrophy were documented at 2 (SD = 2.7) years. CONCLUSION: Children ≤3 years of age in our cohort safely underwent LH with similar pain scores, complications, and recurrence as OH. Parents and caregivers report high satisfaction with both techniques.

Pancreatic surgery for tumors in children and adolescents.

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.

Patient Satisfaction After Minimally Invasive Repair of Pectus Excavatum in Adults: Long-Term Results of Nuss Procedure in Adults.

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.

Ultrasound-Guided Percutaneous Central Venous Access in Low Birth Weight Infants: Feasibility in the Smallest of Patients.

PURPOSE: The insertion of tunneled central venous access catheters (CVCs) in infants can be challenging. The use of the ultrasound-guided (UG) approach to CVC placement has been reported in adults and children, but the technique is not well studied in infants. SUBJECTS AND METHODS: A retrospective review was performed of infants under 3.5 kg who underwent attempted UG CVC placement between August 2012 and November 2013. All infants underwent UG CVC placement using a standard 4.2-French or 3.0-French CVC system (Bard Access Systems, Inc., Salt Lake City, UT). The UG approach was performed on all infants with the M-Turbo(®) ultrasound system (SonoSite, Inc., Bothell, WA). The prepackaged 0.025-inch-diameter J wire within the set was used in all infants weighing greater than 2.5 kg. A 0.018-inch-diameter angled glidewire (Radiofocus(®) GLIDEWIRE(®); Boston Scientific Inc., Natick, MA) was used in infants less than 2.5 kg. Data collected included infant weight, vascular access site, diameter of cannulated vein (in mm), and complications. RESULTS: Twenty infants underwent 21 UG CVC placements (mean weight, 2.4 kg; range, 1.4-3.4 kg). Vascular CVC placement occurred at the following access sites: 16 infants underwent 17 placements via the right internal jugular vein, versus 3 infants via the left internal jugular vein. The average size of the target vessel was 4.0 mm (range, 3.5-5.0 mm). One infant had inadvertent removal of the UG CVC in the right internal jugular vein on postoperative Day 7. This infant returned to the operating room and underwent a successful UG CVC in the same right internal jugular vein. There were no other complications in the group. CONCLUSIONS: The UG CVC approach is a safe and efficient approach to central venous access in infants as small as 1.4 kg. Our experience supports the use of a UG percutaneous technique as the initial approach in underweight infants who require central venous access.

Contemporary management of recurrent pectus excavatum.

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.

Z-type pattern pectus excavatum/carinatum in a case of Noonan syndrome.

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.

Minimally invasive repair of pectus excavatum: analyzing contemporary practice in 50 ACS NSQIP-pediatric institutions.

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.

A randomized trial of laparoscopic versus open Nissen fundoplication in children under two years of age.

AIMS: The surgery of gastroesophageal reflux disease (GERD) is common in modern pediatric surgical practice. Any differences in perioperative and long-term clinical outcomes following laparoscopic (LN) or open Nissen (ON) fundoplication have not been comprehensively described in young children. This randomized, prospective study examines outcomes following LN versus ON in children<2 years of age. METHODS: Four surgeons at a single institution enrolled patients under 2 years of age that required surgical management of GERD, who were then randomized to LN or ON between 2005 and 2012. A universal surgical dressing was employed for blinding. Analgesia and enteral feeding pathways were standardized. The primary outcome was postoperative length of stay. Perioperative outcomes and long-term follow up were collected as secondary outcomes and used to compare groups. RESULTS: Of 39 enrolled patients, 21 were randomized to ON and 18 to LN. Length of postoperative hospital stay, time of advancement to full enteral feeds, and analgesic requirements were not significantly different between treatment cohorts. The LN group experienced longer median operating times (173 vs 91 min, P<0.001) and higher surgical charges ($4450 vs $2722, P=0.002). The incidence of post-discharge complications did not differ significantly between the groups at last follow-up (median 42 months). CONCLUSIONS: This randomized trial comparing postoperative outcomes following LN vs ON did not detect statistically significant differences in short- or long-term clinical outcomes between these approaches. LN was associated with longer surgical time and higher operating room costs. The benefits, risks, and costs of laparoscopy should be carefully considered in clinical pediatric surgical practice.

A novel continuous stitch fundoplication utilizing knotless barbed suture in children with gastroesophageal reflux disease: a pilot study.

INTRODUCTION: The intracorporeal placement and tying of suture (IT) can be challenging leading to prolonged CO2 insufflation, anesthesia, and potential morbidity. The unidirectional barbed knotless suture (V-LOC) has emerged as an innovative technology that has been shown to reduce the time associated with IT. Therefore, we conducted a retrospective analysis comparing our initial experience utilizing V-LOC to perform a novel continuous stitch laparoscopic fundoplication (CF) to standard laparoscopic Nissen fundoplication (NF). METHODS: Institutional review board approval was obtained to analyze data on patients who underwent V-LOC CF and NF. Data retrieval included age, gender, weight, diagnosis, procedure, operative time, major complications (reoperation for wrap failure/migration or recurrent symptoms), and follow up. RESULTS: Twenty patients underwent the V-LOC CF and gastrostomy placement (GT) from January to October 2013. Seventeen patients underwent NF and GT from March 2012 to February 2013. There were no significant differences in age, weight, or incidence of major complications. V-LOC CF led to a significant 30% reduction in operative time compared to NF (79.1±24.2 min vs. 113.8±25.9 min, respectively, P<0.05). CONCLUSIONS: This is the first report documenting the continuous stitch fundoplication utilizing the unidirectional barbed knotless suture in children. Although follow-up is short, the V-LOC CF appears to be a safe and effective technique that may reduce operative time in children with gastroesophageal reflux disease. This technology may be beneficial in other minimally invasive applications in pediatric surgery.

Thymectomy for myasthenia gravis in children: a comparison of open and thoracoscopic approaches.

PURPOSE: Thymectomy is an accepted component of treatment for myasthenia gravis (MG), but optimal timing and surgical approach have not been determined. Though small series have reported the feasibility of thoracoscopic resection, some studies have suggested that minimally invasive methods are suboptimal compared to open sternotomy owing to incomplete clearance of thymic tissue. Here we report the largest series of thymectomies for pediatric myasthenia gravis in the literature to date. METHODS: A retrospective review of patients undergoing thymectomy for MG between 1990 and 2013 in a tertiary referral hospital was performed. Twelve patients who underwent thoracoscopic thymectomy were compared to 16 patients who underwent open thymectomy via median sternotomy. Postoperative outcomes were determined by electronic chart review in consultation with the treating pediatric neurologist. Disease severities were graded according to a modified Myasthenia Gravis Foundation of America (MGFA) Quantitative MG (QMG) score. RESULTS: Overall, thoracoscopic resections tended to be performed on patients with earlier and less severe disease than open surgeries. Inpatient length of stay was significantly shorter after thoracoscopic surgery (mean 1.8 vs 8.0 days, p=0.045). The preoperative and postoperative MGFA QMG scores were equivalent between the two groups. Both groups experienced a decrease in disease severity (p<0.001) after median follow-up time of 23 months in the thoracoscopic group and 44 months in the open group. CONCLUSIONS: Minimally invasive thymectomy for MG in children has increased in popularity as surgeons and neurologists compare the risks and benefits of surgery against other therapies. This analysis suggests that thoracoscopic thymectomy is not inferior to median sternotomy in terms of disease control in this small series, and that the morbidity of the thoracoscopic approach appears sufficiently low to be considered for early stage disease. Low perioperative morbidity and shortened hospital course make thoracoscopic thymectomy an attractive option in centers with sufficient medical and surgical experience.

Choosing the order of deceased donor and living donor kidney transplantation in pediatric recipients: a Markov decision process model.

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.

A nipple-valve technique for ureteroneocystostomy in pediatric kidney transplantation.

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.

Do prehospital criteria optimally assign injured children to the appropriate level of trauma team activation and emergency department disposition at a level I pediatric trauma center?

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.

Perioperative strategies and technical modifications to the Nuss repair for pectus excavatum in pediatric patients: a large volume, single institution experience.

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.

National trends over 25 years in pediatric kidney transplant outcomes.

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.

Hydrogen sulfide [corrected] increases survival during sepsis: protective effect of CHOP inhibition.

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.