Surgical management of pediatric adhesive bowel obstruction.
The objective of this study was to analyze a population-based database for recent trends in surgical management of pediatric adhesive bowel obstruction and compare open versus laparoscopic lysis of adhesions (LOA).



Pediatric adhesive bowel obstruction cases were identified in the Kids' Inpatients Database from 1997, 2000, 2003, 2006, and 2009. Data analysis included patients' demographics, hospital variables, length of stay (LOS), and total hospital charges (THC). Complications analysis included postoperative shock, hemorrhage, hematoma, seroma, wound complications, infection, fistula, and pulmonary complications.



In total, 20,679 pediatric adhesive bowel obstruction cases were identified during the study period. These were characterized by a median age of 11 years old, with 59.0% of the population female. Overall treatment included 88.6% open and 11.4% laparoscopic LOA. A more than twofold increase in utilization of laparoscopy was observed from 7.2% in 1997 to 17.2% in 2009 (P<.001). Complication rates were lower for laparoscopic LOA versus open (5.6% versus 10.4%; odds ratio 0.512; 95% confidence interval 0.394-0.667; P<.001), especially accidental puncture or laceration rate (2.2% versus 3.9%; odds ratio 0.566; 95% confidence interval 0.375-0.854; P=.006). Conversion to open LOA occurred in 1.9%. Laparoscopy was associated with a shorter median LOS (6 versus 8 days; P<.001) and a lower mean THC ($38,241.11 versus $48,552.51; P<.001) compared with open LOA. Multivariate regression analysis did not find hospital bed size, location, teaching status, and regions to be statistically significant predictors for utilization of laparoscopy.



Laparoscopic LOA is a safe option for pediatric adhesive bowel obstruction with lower complication rates and a reduced economic burden. Despite the increase in utilization of laparoscopy in recent years, only a minority of patients underwent laparoscopic LOA. Further studies are needed to identify and characterize the subgroup of patients who benefit from laparoscopic LOA.

title: Is partial colectomy the operation of choice in pediatric Clostridium difficile colitis?
abstract: PurposeThis study examined the national trends in incidence and surgical management of pediatric Clostridium difficle colitis (CDC) hospitalizations.MethodsThis was a cross-sectional Nationwide Inpatient Sample (NIS) analysis of pediatric CDC from 2000 to 2008. Data analysis included patient demographics, procedures, length of stay (LOS), total hospital charges (THC), and in-hospital mortality.ResultsDuring the 9-year study period, the total number of CDC hospitalizations per year increased almost twofold, from 2,513 in 2000 to 4,817 in 2008. The rate per 100,000 discharges followed a similar trend, increasing from 38.08 in 2000 to 72.57 in 2008. Abdominal colectomy was performed in 0.35 %, with partial colectomy performed more often than total colectomy. Mortality, mean LOS, and mean THC were not statistically different between partial versus total colectomy. Children with ulcerative colitis were more likely to undergo total colectomy, (OR 35.700, CI 11.025–115.98, P < 0.001). Infants under the age of 1 year were less likely to undergo total colectomy (OR 0.568, 0.477–0.677, P < 0.001).ConclusionPediatric hospitalizations for CDC are on the rise. Partial colectomy is performed more often than total colectomy without statistical compromise of mortality, length of stay, and total hospital charges. Further studies are needed to determine the standard surgical management of pediatric CDC.

title: Missed opportunities in the treatment of pediatric appendicitis
abstract: IntroductionThis study sought to evaluate the outcomes of in-hospital delay and determine associated co-morbidities in the treatment of pediatric acute appendicitis.MethodsThis was a retrospective analysis of the national inpatient sample from 2000 to 2008. Immediate treatment was defined as treatment in hospital day 0 or 1. Delay in treatment was defined as treatment in hospital day 2 and beyond.ResultsDuring the study period, 683,016 pediatric appendicitis were identified. 17,737 (2.6 %) experienced a delay in treatment. Multivariate analysis identified associated co-morbidities for delay in treatment: ALL (OR 12.84, CI 11.04–14.94), AML (OR 9.41, CI 7.58–11.68), neutropenia (OR 5.53, CI 4.60–6.65), and ovarian cyst without torsion (OR 3.17, CI 2.94–3.42). Surgical management included more than 13-fold increase in drainage procedures (5.5 vs. 0.4 %), sixfold increase in cecectomy (1.2 vs. 0.2 %), 14-fold increase in hemicolectomy (1.4 vs. 0.1 %), 11-fold increase in small bowel laceration suture repair (1.1 vs. 0.1 %), and 15-fold increase in small bowel resection (1.5 vs. 0.1 %).ConclusionsIn-hospital delay beyond 2 days is associated with significant negative outcomes with regard to complications, economic burden, and subsequent surgical management. Using the co-morbidity index, high-risk co-morbidities with associated delay in treatment were identified.

title: Less is more: management of pediatric splenic injury.
abstract: To analyze national trends in the nonoperative management of pediatric splenic injury.



Retrospective cohort analysis.



All children and adolescents 18 years or younger from 2 national databases who were hospitalized with pediatric splenic injury.



Data from 9 years of the National Inpatient Sample database (2000-2008) and 3 years of Kids' Inpatient Database (2000, 2003, and 2006).



We calculated and chronicled rates of splenectomy, angiography, and transfusion from 2000 to 2008.



During the study period, the rate of splenectomy decreased from 18.25% to 10.86%. Changes in nonoperative management included more than a 2-fold increase in angiography, from 2.43% to 6.94%, and a significant increase in transfusion, from 7.71% to 11.49%. Operative management was associated with increased length of stay (9.15 vs 6.52 days) and higher mean total hospital charges ($74 981.26 vs $36 156.30). Cases occurring in rural locations were more likely to undergo operative management (odds ratio, 1.24 [95% CI, 1.18-1.31]; P < .001), but less likely to undergo angiography (0.82 [0.76-0.89]; P < .001).



Children with pediatric splenic injury are undergoing fewer splenectomies but more angiography. Rural location may be an independent risk factor for operative management. Further studies are needed to assess for disparity in access to and availability of aggressive nonoperative management.

title: Guns and states: pediatric firearm injury.
abstract: A recent report indicates that firearm-related injuries are responsible for 30% of pediatric trauma fatality. The literature is however limited in examining pediatric firearm injuries and variations in state gun control laws. Therefore, we sought to examine the association between pediatric firearm injuries and the Stand-Your-Ground (SYG) and Child Access Protection (CAP) laws.



All pediatric (age, 0-20 years) hospitalizations with firearm injuries were identified from the Kids' Inpatient Database from 2006 and 2009. States were compared for SYG and CAP laws.



A total of 19,233 firearm injury hospitalizations were identified, with 64.7% assault, 27.2% accidental, and 3.1% suicide injury. Demographics for assault injury were as follows: mean age of 17.6 years, 88.4% male, 44.4% black, 18.2% Hispanic, 70.5% from metropolitan areas, and 50.1% from the poorest median income neighborhoods. Suicide injury cases were more likely to be white (57.8% vs. 16.6%, p < 0.001) and female (15.1% vs. 9.8%, p < 0.001). States with the SYG law were associated with increased accidental injury (odds ratio [OR], 1.282; p < 0.001). There was no statistical association between CAP law and the incidence of accidental injury or suicide. Multivariate logistic regression analysis found other predictive demographic factors for firearm injury: black (OR, 6.164), urban areas (OR, 1.557), poorest median income neighborhoods (OR, 2.785), male (OR, 28.602), and 16 years or older (OR, 37.308). Total economic burden was estimated at more than $1 billion dollars, with a median length of stay of 3 days, 8.4% discharge to rehabilitation, and 6.2% in-hospital mortality.



Pediatric firearm injuries continue to be a significant source of morbidity, mortality, and economic burden. A significant increase in accidental firearm injuries in states with the SYG law may highlight inadvertent effects of the law. Race, sex, and median income are additional contributing factors. Advocacy and focused educational efforts for specific socioeconomic and racial groups may potentially reduce firearm injuries.



Prognostic study, level II.

title: Gallbladder damage control: compromised procedure for compromised patients
abstract: BackgroundThe objective of this study was to analyze a population-based database for (1) recent 9-year trends in utilization of partial cholecystectomy (PC), laparoscopic PC, and trocar cholecystostomy (TC), (2) demographics, associated diagnoses, and hospital characteristics, and (3) relevant inpatient outcomes.MethodsRetrospective cohort analysis of the Nationwide Inpatient Sample (NIS) files from 2000 to 2008 was performed. For the purposes of the study, gallbladder damage control was defined as PC, laparoscopic PC, and TC.ResultsA national estimate of 10,872 gallbladder damage control cases was obtained. Procedures performed included PC (47.8 %), laparoscopic PC (27.2 %), TC (25.3 %), and intraoperative cholangiogram (IOC) (19.7 %). A total of 1,479 (13.6 %) postoperative complications were identified, including pulmonary complications (4.3 %), hemorrhage/hematoma/seroma (3.4 %), and accidental puncture or laceration during procedure (3.3 %). Common bile duct injury occurred in 3.3 % overall. Hospital types included nonteaching (82.1 %) and urban (67.8 %), with regional variations of 42.1 % from the South and 45.2 % from the West. Inpatient outcomes included mean length of stay of 11.4 (0.16 SEM) days, mean total hospital charge of $71,296.69 ($1,106.03 SEM), 7.4 % mortality, and 16.8 % discharge to skilled nursing facility. Multivariate logistic regression analysis identified independent risk variables for common bile duct injury: teaching hospitals (OR = 1.517, CI = 1.155–1.991, P = 0.003). IOC (OR = 2.030, CI = 1.590–2.591, P < 0.001) was a commonly associated procedure in the setting of common bile duct injury.ConclusionVarious circumstances may require gallbladder damage control with PC and TC. Postoperative complications and common bile duct injury remain significantly high despite limited resection, and the teaching status of the hospital is associated with CBD injury. High morbidity and mortality of gallbladder damage control may reflect both the compromised nature of the procedures and multiple comorbidities.

title: Extended dosing of etanercept 25 mg can be effective in patients with ankylosing spondylitis: a retrospective analysis
abstract: As a measure of healthcare cost containment, the total number of vials of entanercept (25 mg) that can be prescribed for patients with inflammatory arthritis is restricted in Korea. Consequently, attempts to extend the dosing interval while maintaining the efficacy have not been an uncommon clinical practice. The aim of this study was to determine if extended doing interval of etanercept can be effective in patients with ankylosing spondylitis (AS). We performed a retrospective analysis using medical records at a single tertiary hospital. One hundred and nine patients with AS and 79 patients with rheumatoid arthritis (RA) started on etanercept between November 2004 and November 2009 were indentified. Etanercept (25 mg) was started with twice-weekly dosing schedule. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), C-reactive protein (CRP), and etanercept dosing interval for AS patients at 0, 3, 9, 15, 21 months were reviewed. Dosing interval for RA patients was analyzed for comparison. In AS, mean dosing interval was 4.7 ± 2.1 days at 3 months and was increased to 12.1 ± 7.0 days at 21 months. Despite the progressive increase in the dosing interval, the mean BASDAI declined rapidly at 3 months, and continued to decrease over 21 months. Mean CRP declined after 3 months of therapy and remained low thereafter. In RA, mean dosing interval was 4.0 ± 1.2 days at 3 months and 5.1 ± 1.8 days at 21 months. In conclusion, in AS, extended dosing of etanercept can be effective without compromising clinical and laboratory markers of disease activity as measured by BASDAI and CRP, respectively. Tapering of etanercept was less accommodating in RA when compared to AS.

title: Quantitative measures of facial expression for patients with head and neck cancer
abstract: In addition to changes in facial morphology, head and neck cancer treatment can impact the facial expression. Quantification of changes in facial expression, particularly of smiling, would enable a deeper understanding of the relationship between physical changes and psychosocial adjustment in patients being treated for facial cancer. This study proposes 48 quantitative facial expression measures, which consist of the length normalized distances and slopes between 27 manually annotated fiducial points on standard 2D clinical photographs of patients with head and neck cancer. Using the proposed measures, the maximum intensity of smiling for patients with head and neck cancer prior to their treatments was compared to that of a sample from a healthy population. A total of 7 facial expression measures captured statistically significant differences between patients with head and neck cancer and healthy individuals. These measures suggest that patients with head and neck cancer are less expressive than people without head and neck cancer. This study is the first attempt to quantify the facial expression of patients with head and neck cancer and to build a foundation for studying how surgical interventions may affect their facial expressions. Moreover, this study lays the groundwork for future investigation of the relationship between facial expression and psychosocial adjustment in cancer patients.

title: Murine vibrissae cultured in serum-free medium reinitiate anagen.
abstract: Aberrant regulation of the hair cycle has been implicated in human boldness (Reviewed in (Nakamura et al, 2001; Paus and Cotsarelis, 1999)). Although several modulators of mammalian hair follicle cycle have been recently described, discovery of effective treatment for boldness has suffered from the absence of a reliable in vitro culture systems in which the hair cycle can be assessed easily and inexpensively (Stenn and Paus, 2001). Several laboratories have established serum-free culture system where vibrissa can grow and differentiate in vitro (Supplemental Table 1, (Jindo et al, 1993; Robinson et al, 1997; Yano et al, 2001). Although rat vibrissae cultured for 23 days were reported to share histological similarities with catagen or pro-anagen (telogen) stage follicles (Philpott and Kealey, 2000), these follicles did not show any progress beyond pro-anagen phase nor did they produce a new hair shaft (Philpott and Kealey, 2000). In this report, we demonstrate that a simple modification permits murine vibrissae in the current in vitro culture system to reinitiate anagen. This will accelerate the development of screening systems aimed at modifying the hair cycle. 
 
To establish a modified in vitro vibrissa culture system, anagen-stage vibrissae were carefully isolated from 14-day-old mice and the tip of the vibrissa shafts were anchored in a stripe of sterilized silicone grease placed on the culture dish through a 3 ml syringe. The plate was then filled with serum-free medium (Figure 1a, Supplemental Material and Method). Out of 86 cultured vibrissae collected from three pups, 81 vibrissae (94%) showed measurable shaft growth (Table 1, Figure 1b). Two of 81 vibrissae were lost, and 17 developed abnormal (kinked) fiber and were omitted from growth measurement. Of the remaining 62 vibrissae, straight shafts were produced by all at a rate of 0.3–0.5mm/day for the first three days. While some follicles maintained this growth rate through the fifth day of culture (Figure 1b and 1c and data not shown), others began a gradual decline in growth rate (Figure 1b and 1c, ​,2a2a and data not shown). As previously reported (Jindo et al, 1993; Robinson et al, 1997), growth rates of all follicles slowed down considerably after 5 days in culture, indicating independence from culture conditions (Supplemental Table 1). 
 
 
 
Figure 1 
 
Vibrissae produce hair shafts and reinitiate anagen in serum-free culture medium 
 
 
 
 
 
Figure 2 
 
Histological and immunohistochemical characteristics of new anagen follicles 
 
 
 
 
 
Table 1 
 
Summary of the in vitro vibrissa culture 
 
 
 
Hair shaft elongation rate decreases and eventually stops when follicles enter catagen/telogen phase in vivo (Alonso and Fuchs, 2006). Several days after cessation of hair shaft growth, cultured vibrissae follicles continuously changed their morphology, at times visible through their collagen capsules . Strikingly, dissection and removal of collagen capsules from 21-day-cultured vibrissae revealed that all vibrissae produced a second shaft (Figures 1d and 2a–h, arrows; Figure S1), readily distinguishable from the original shaft whose proximal end formed club-end indicative of a completed catagen (Figures 1 and ​and22 closed arrowheads). Histological and immunohistochemical analyses using AE13, a marker for cortex/cuticle specific keratins, confirmed the formation of new hair shafts (Figures 2c–f and S1). The new shafts were produced in proximal bulbs that appeared smaller in size than the original ones before culture. Since the original hair growth stopped within the first 5 days of culture, and since a new shaft emerges from a secondary bulb, we concluded that vibrissa follicles from CD1 mice reinitiated anagen phase by regenerating hair bulbs . Staining for alkaline phosphatase activity identified an intact (but small) dermal papilla within the new bulb ; Young and Oliver, 1976). Moreover, the hair matrix cells were positive for Ki-67, a proliferation marker, even after 13 days in culture (Figure 2h), indicating that the formation of new shaft was the result of active proliferation and differentiation of matrix cells in cultured vibrissae. Similar cycling patterns were also observed with vibrissae from 14-day-old C57BL/6 mice , indicating that hair cycle in vitro is independent of mouse strains. 
 
To better visualize the hair cycle process, we next performed vibrissae culture after careful removal of their collagen capsules . Within 2 days, the proximal end of the vibrissa keratinized, forming a club hair, at which time dermal papilla structures were no longer discernable (Figure 2i and data not shown). A day later, however, a bud-like structure emerged from the proximal part of the bulb in eight of ten cultured vibrissae. Of these, one vibrissa continued growing outwards, eventually forming a new bulb producing a vibrissa thinner than the club hair . Strikingly, we observed that this vibrissa appeared to enter a third anagen, producing a new bud from the second bulb . Collectively, the data presented here indicate that in our in vitro culture system, vibrissa follicles enter a second anagen phase and it may be possible for a few to enter a third cycle in culture. 
 
We are not certain which modification in our culture system permits vibrissae to cycle. We do not think this is caused by differences in media composition, mouse strain, or frequency of media change. Our attempt to grow vibrissae at the air-fluid interface as in (Jindo et al, 1993) showed that one of five vibrissae formed a new hair shaft (Figure S3, Arrows), indicating that hair cycle is not strictly dependent on culture media or on the frequency of media change. However, we observed that on a solid substrate most vibrissae gradually lost their hair matrix possibly due to a pressure caused by friction generated while extending a hair shaft on a solid surface or in the absence of sebum (Sundberg et al, 2000) . Although not proven, we speculate that the critical modification was our method of immobilizing the hair shaft in silicon grease that provided friction-free environment; anchoring the tip of shafts may have allowed gravity to facilitate the separation of club hairs from the hair matrix and that supports new hair shaft formation. In addition, the smaller size of mouse vibrissae, in comparison with human or rat vibrissae, could also be a contributing factor in the anagen reinitiation in vitro As this culture system is the first to support reinitiation of anagen in culture dish, we hope this improvement will expedite the testing and development of hair cycle modifying pharmaceuticals.

title: Akt mediates self-renewal division of mouse spermatogonial stem cells
abstract: Spermatogonial stem cells have unique properties to self-renew and support spermatogenesis throughout their lifespan. Although glial cell line-derived neurotrophic factor (GDNF) has recently been identified as a self-renewal factor for spermatogonial stem cells, the molecular mechanism of spermatogonial stem cell self-renewal remains unclear. In the present study, we assessed the role of the phosphoinositide-3 kinase (PI3K)-Akt pathway using a germline stem (GS) cell culture system that allows in vitro expansion of spermatogonial stem cells. Akt was rapidly phosphorylated when GDNF was added to the GS cell culture, and the addition of a chemical inhibitor of PI3K prevented GS cell self-renewal. Furthermore, conditional activation of the myristoylated form of Akt-Mer (myr-Akt-Mer) by 4-hydroxy-tamoxifen induced logarithmic proliferation of GS cells in the absence of GDNF for at least 5 months. The myr-Akt-Mer GS cells expressed spermatogonial markers and retained androgenetic imprinting patterns. In addition, they supported spermatogenesis and generated offspring following spermatogonial transplantation into the testes of infertile recipient mice, indicating that they are functionally normal. These results demonstrate that activation of the PI3K-Akt pathway plays a central role in the self-renewal division of spermatogonial stem cells.

title: Successful cyclophosphamide therapy with complete resolution of pulmonary artery aneurysm in Hughes–Stovin syndrome patient
abstract: Hughes–Stovin syndrome is an exceedingly rare disorder of unknown etiology, and it is characterized by multiple pulmonary artery aneurysms and peripheral venous thrombosis. We report a case of Hughes–Stovin syndrome with complete resolution of pulmonary artery aneurysm after treatment with cyclophosphamide. A 48-year-old man presented with massive hemoptysis, fever, and weight loss of 4-month duration. Computed tomography angiography revealed multiple pulmonary arterial aneurysms of variable sizes in both lung fields. Inferior vena caval thrombosis was also noted. Despite multiple surgical procedures including embolectomy and lobectomy combined with steroid therapy, new aneurysms continued to appear with persistent hemoptysis. Thorough history and physical examination did not suggest any evidence of Behcet’s disease. Hughes–Stovin syndrome was subsequently diagnosed. High-dose prednisolone combined with oral cyclophosphamide therapy was initiated. Chest radiography follow-up in 3 months revealed complete resolution of pulmonary aneurysm. No new aneurysm was detected at 15 months of follow-up.