Jejunoileal mucosal growth in mice with a limited microbiome.

Previous work demonstrated enhanced enterocyte proliferation and mucosal growth in gnotobiotic mice, suggesting that intestinal flora participate in mucosal homeostasis. Furthermore, broad-spectrum enteral antibiotics are known to induce near germ-free (GF) conditions in mice with conventional flora (CONV). We hypothesized that inducing near GF conditions with broad-spectrum enteral antibiotics would cause ordered small intestinal mucosal growth in CONV mice but would have no effect in GF mice with no inherent microbiome. C57BL/6J CONV and GF mice received either an antibiotic solution (Ampicillin, Ciprofloxacin, Metronidazole, Vancomycin, Meropenem) or a vehicle alone. After treatment, small intestinal villus height (VH), crypt depth (CD), mucosal surface area (MSA), crypt proliferation index (CPI), apoptosis, and villus and crypt cell types were assessed. Antibiotic-treated CONV (Abx-CONV) mice had taller villi, deeper crypts, increased CPI, increased apoptosis, and greater MSA compared to vehicle-treated CONV mice. Minor differences were noted in enterocyte and enterochromaffin cell proportions between groups, but goblet and Paneth cell proportions were unchanged in Abx-CONV mice compared to vehicle-treated CONV mice (p>0.05). Antibiotics caused no significant changes in VH or MSA in GF mice when compared to vehicle-treated GF mice (p>0.05). Enteral administration of broad-spectrum antibiotics to mice with a conventional microbiome stimulates ordered small intestinal mucosal growth. Mucosal growth was not seen in germ-free mice treated with antibiotics, implying that intestinal mucosal growth is associated with change in the microbiome in this model.

Symptomatic use of carbidopa in autonomic disorders.

Carbidopa is being explored as a novel therapy for hyperadrenergic symptoms of autonomic disorders, due to its potential to decrease peripheral catecholamine levels. This study retrospectively characterized patients in our autonomic clinic who were prescribed carbidopa for open label treatment of autonomic symptoms. 23 patients were included; approximately half had postural orthostatic tachycardia syndrome. Those with documented plasma catecholamines had elevated standing norepinephrine. Patients typically had multiple comorbidities and multiple failed therapies. 19 took carbidopa (typically 25 mg three times daily); 12 continued it for longer than 3 months. 11 patients reported better symptom control with carbidopa, most commonly tremor and gastrointestinal dysfunction. 4 patients reported side effects. In this small retrospective study, carbidopa was well tolerated in patients with dysautonomia, and half reported symptomatic benefit. Larger, placebo-controlled trials are warranted for further investigation of this therapy.

Serotonin as a Mitogen in the Gastrointestinal Tract: Revisiting a Familiar Molecule in a New Role.

Serotonin signaling is ubiquitous in the gastrointestinal (GI) system, where it acts as a neurotransmitter in the enteric nervous system (ENS) and influences intestinal motility and inflammation. Since its discovery, serotonin has been linked to cellular proliferation in several types of tissues, including vascular smooth muscle, neurons, and hepatocytes. Activation of serotonin receptors on distinct cell types has been shown to induce well-known intracellular proliferation pathways. In the GI tract, potentiation of serotonin signaling results in enhanced intestinal epithelial proliferation, and decreased injury from intestinal inflammation. Furthermore, activation of the type 4 serotonin receptor on enteric neurons leads to neurogenesis and neuroprotection in the setting of intestinal injury. It is not surprising that the mitogenic properties of serotonin are pronounced within the GI tract, where enterochromaffin cells in the intestinal epithelium produce 90% of the body's serotonin; however, these proliferative effects are attributed to increased serotonin signaling within the ENS compartment as opposed to the intestinal mucosa, which are functionally and chemically separate by virtue of the distinct tryptophan hydroxylase enzyme isoforms involved in serotonin synthesis. The exact mechanism by which serotonergic neurons in the ENS lead to intestinal proliferation are not known, but the activation of muscarinic receptors on intestinal crypt cells indicate that cholinergic signaling is essential to this signaling pathway. Further understanding of serotonin's role in mucosal and enteric nervous system mitogenesis may aid in harnessing serotonin signaling for therapeutic benefit in many GI diseases, including inflammatory bowel disease, malabsorptive conditions, and cancer.

Reducing Underdiagnosis of Hirschsprung-Associated Enterocolitis: A Novel Scoring System.

BACKGROUND: Hirschsprung-Associated Enterocolitis (HAEC) is a life-threatening and difficult to diagnose complication of Hirschsprung Disease (HSCR). The goal of this study was to evaluate existing HAEC scoring systems and develop a new scoring system. METHODS: Retrospective, multi-institutional data collection was performed. For each patient, all encounters were analyzed. Data included demographics, symptomatology, laboratory and radiographic findings, and treatments received. A "true" diagnosis of HAEC was defined as receipt of treatment with rectal irrigations, antibiotics, and bowel rest. The Pastor and Frykman scoring systems were evaluated for sensitivity/specificity and univariate and multivariate logistic regression performed to create a new scoring system. RESULTS: Four centers worldwide provided data on 200 patients with 1450 encounters and 369 HAEC episodes. Fifty-seven percent of patients experienced one or more episodes of HAEC. Long-segment colonic disease was associated with a higher risk of HAEC on univariate analysis (OR 1.92, 95% CI 1.43-2.57). Six variables were significantly associated with HAEC on multivariate analysis. Using published diagnostic cutoffs, sensitivity/specificity for existing systems were found to be 38.2%/96% for Pastor's and 56.4%/86.9% for Frykman's score. A new scoring system with a sensitivity/specificity of 67.8%/87.9% was created by stepwise multivariate analysis. The new score outperformed the existing scores by decreasing underdiagnosis in this patient cohort. CONCLUSIONS: Existing scoring systems perform poorly in identifying episodes of HAEC, resulting in significant underdiagnosis. The proposed scoring system may be better at identifying those underdiagnosed in the clinical setting. Head-to-head comparison of HAEC scoring systems using prospective data collection may be beneficial to achieve standardization in the field.

National Survey of Pediatric Intestinal Rehabilitation Programs in the United States.

BACKGROUND: Pediatric intestinal rehabilitation (PIR) programs are associated with improved outcomes in children with intestinal failure but remain heterogeneous nationally. This study characterizes PIR program components to aid those seeking to establish or expand a program. METHODS: Members of the Children's Hospital Association reporting a PIR program to the US News and World Report completed a 14-item questionnaire using the Qualtrics Online Survey Software. Programs were categorized as small or large (≤50 vs >50 patients) and new or established (≤10 vs >10 years). RESULTS: Seventy-one programs were identified and 61 surveys were returned for a response rate of 86%. Majority of programs had gastroenterology, surgery, nutrition, nursing, and social work services involved. Large programs (n = 34; 59%) were more likely to serve as referral centers; have greater participation by nursing, social work, and primary care; have more dedicated time by gastroenterology, surgery, nursing, nutrition, and social work; have more frequent meetings; and have various funding sources (P < .05). CONCLUSION: Critical components of a PIR program include gastroenterology, surgery, and nutrition services with strong nursing and social work support. These data document the components of modern PIR programs, though further studies on the relationship between program structure and patient outcomes are warranted.

Mucosal characteristics vary across developmental stages in the small intestine of C57BL/6J mice.

AIMS: The benefits of utilizing laboratory mice include low cost, ease of maintenance, and accessibility of molecular tools. However, the ages of experimental mice in the literature vary drastically. We hypothesized that there exists age-related variation in the murine small intestine across developmental stages. MATERIALS AND METHODS: Segments of small intestine were harvested from C57BL/6J mice of varying ages (E17 to 24 weeks; n = 3-4/group). Slides were analyzed for morphometric parameters, cell types, and crypt proliferation index (CPI). Secondary analysis comparing age-matched males and females (n = 4/group) was performed. Means were compared with Student's t-test and variance of proportions with the Chi-squared test to a significance of p < 0.05. KEY FINDINGS: There were small but significant differences including regional variation in villus height, which abolished when examining the small intestine as a whole. Sexually immature mice had increased CPI compared to mature animals. The most dramatic differences were seen in mice at weaning, which demonstrated shallower crypts, increased CPI, fewer Paneth and goblet cells, and more enterochromaffin cells. Examination of embryonic intestine revealed an underdeveloped mucosa lacking differentiated cells. There were minimal differences when comparing age-matched males and females. SIGNIFICANCE: Small, but statistically significant differences in villus height, crypt depth, and crypt proliferation are present in mice across early developmental stages. Mice at weaning exhibit variation in crypt-villus cell composition compared to older animals, which may explain the propensity for certain intestinal conditions in the very young. Investigators studying the GI mucosa should employ consistent age-matching in order to allow direct comparison between studies.

Outcomes of neonates with listeriosis supported with extracorporeal membrane oxygenation from 1991 to 2017.

BACKGROUND: Listeriosis may cause severe disease in fetuses and neonates. The outcomes of critically ill neonates with early-onset listeriosis requiring extracorporeal membrane oxygenation (ECMO) from 1975 to 1991 have been reported. OBJECTIVE: To update the characteristics and outcomes of neonates with listeriosis supported by ECMO. STUDY DESIGN: Retrospective study of neonates with culture-proven listeriosis reported to the Extracorporeal Life Support Organization Registry between 1991 and 2017. Comparisons were made between this cohort and the case series from 1975-1991. RESULTS: Twenty-two neonates had culture-proven Listeria monocytogenes infection and required ECMO support. Eight-six percent survived to discharge, compared with 67% in the previous cohort (p = 0.2). The median ECMO duration was 131 h, compared with 209 h in the previous cohort (p = 0.1). Nonsurvivors had a significantly lower pre-ECMO pH (6.91 vs 7.31, p = 0.0006). CONCLUSION: The survival of neonates with listeriosis supported with ECMO is high, supporting the use of ECMO as rescue therapy for this condition.

Identification of an occult recto-prostatic fistula with cystoscopy-assisted air colostogram.

INTRODUCTION: Anorectal malformations (ARM) in newborns classically present with the absence of a normal anus or an abnormally located anus. In a male infant with a high ARM, an initial diverting colostomy is later followed by a definitive posterior sagittal anorectoplasty (PSARP). Prior to definitive surgery an augmented-pressure colostogram is performed to identify the location of the fistula between the rectum and urogenital tract. However, on occasion, the augmented-pressure colostogram fails to identify the location of the fistula tract. We present a case of ARM where augmented-pressure colostogram failed to identify a fistula tract, thus requiring an alternative diagnostic approach. PRESENTATION OF CASE: A newborn male presented with a high anorectal malformation and suspected rectourinary fistula on initial augmented-pressure colostogram. The patient ultimately underwent a laparoscopic assisted PSARP after cystoscopy with air colostogram identified the exact location of the fistulous connection in the prostatic urethra. DISCUSSION: Augmented-pressure colostogram remains the gold standard in diagnosing rectourinary fistulae in cases of ARM. However, a number of alternative and adjunctive techniques have been proposed in recent years. We provide a brief review of the literature in addition to a case presentation highlighting the potential benefits of pre-operative cystoscopy-assisted air colostogram in male patients with ARM. CONCLUSION: Cystoscopy-assisted air colostogram via a distal mucous fistula can be utilized as an alternative diagnostic modality, especially when the augmented-pressure distal colostogram fails to identify rectourinary fistulae in high anorectal malformations.

Serum Citrulline Levels Exhibit Circadian Variation and Fluctuations in Relation to Food Intake in Mice.

BACKGROUND: Plasma citrulline is a nonessential amino acid synthesized almost exclusively by enterocytes of the small intestine. Correlation between post-operative plasma citrulline levels and remnant small bowel mass and function has led to its use as a simple biomarker of functional intestinal mass in adults and children, with a proposed prognostic value for achieving enteral autonomy in the setting of intestinal failure. While it is standard to measure fasting levels in humans, the optimal timing of blood draws in relation to food intake and time of day has not been standardized and is poorly studied in animal models. We hypothesize that serum citrulline levels vary both throughout the day and with relation to food intake in mice. METHODS: Serum citrulline levels were measured from 12 C57BL/6 mice (6 - 9 weeks old) in the mornings and evenings, either after ad libitum food intake or after 8 - 12 h of access to water only. Blood draws for each experimental set-up were performed 1 week apart according to our Institutional Animal Care and Use Committee (IACUC) guidelines for acceptable blood collection volumes for survival procedures. At the end of the experiment, mice were euthanized and small intestine was harvested for morphometric measurements. Group means were compared using Student's t-test with significance assumed for P < 0.05. RESULTS: After withholding chow for 8 - 12 h, serum citrulline levels were significantly greater in the morning compared to levels drawn in the evening. When mice were allowed ad libitum chow, there was no significant difference in serum citrulline levels drawn in the morning compared to the evening. There was no difference detected in villus height across the different experimental conditions. CONCLUSIONS: Serum citrulline levels exhibit circadian variation and fluctuations in relation to food intake in mice, without apparent concurrent changes in enterocyte mass. There was no diurnal variation of serum citrulline levels in fed mice whereas fasted mice had significantly higher levels of serum citrulline in the morning compared to the evening. These findings underscore the paramount importance of consistent sample collection strategies in the setting of translational research.

Trends in Routine and Complex Hepatobiliary Surgery Among General and Pediatric Surgical Residents: What is the Next Generation Learning and is it Enough?

OBJECTIVE: Previous studies reveal a correlation between surgical volume and outcomes; thus, a similar relationship likely exists between trainee operative volume and technical competence. While routine hepatobiliary surgery is commonplace, trainee exposure to the more advanced procedures may be lacking. We hypothesize that experience in complex hepatobiliary procedures may be deficient both during general surgery residency and pediatric surgery fellowship training. DESIGN: Case log data from the ACGME were queried for general surgery residents (2000-2017) and pediatric surgery fellows (2004-2017). Laparoscopic cholecystectomy was considered a routine hepatobiliary procedure for both specialties. For general surgery, hepatic lobectomy/segmentectomy and choledochoenteric anastomosis were considered complex and for pediatric surgery, hepatic lobectomy, biliary atresia and choledochal cyst procedures were considered complex. SETTING: Publicly available case log data from the ACGME. PARTICIPANTS: General surgery residents and pediatric surgery fellows at ACGME-accredited training programs. RESULTS: The number of trainees increased over the study period for both groups. Mean case volumes for laparoscopic cholecystectomy increased by 36% in surgery graduates and by 114% in pediatric surgery graduates. In surgery, the mean volumes for choledochoenteric anastomosis procedures decreased by 53% from 3.0 to 1.4 procedures/year with increasing variability in trainee experience. Volumes for hepatic lobectomy/segmentectomy increased by 68% from 3.4 to 5.7 procedures/year with decreasing variability. In pediatric surgery, case volumes for complex procedures were low (mean <4/year), highly variable among trainees, and appear unchanged between 2004 and 2017. In every year analyzed, at least 1 pediatric surgery trainee reported doing 0 cases in one of these complex categories. CONCLUSIONS: Case logs suggest that the volume of complex hepatobiliary surgery remains low and highly variable in both disciplines with some trainees obtaining minimal or no exposure to certain cases. The relationship between these trends and the development of competency is worthy of further study.

Potentiation of serotonin signaling leads to increased carbohydrate and lipid absorption in the murine small intestine.

BACKGROUND: Enteric serotonin influences intestinal homeostasis and functions as a mucosal growth factor. Previously, we demonstrated increased mucosal surface area and enhanced crypt cell proliferation in serotonin reuptake transporter (SERT)-deficient mice. Therefore, we hypothesized that serotonin-mediated mucosal growth would also result in enhanced carbohydrate and lipid absorption. MATERIAL AND METHODS: Wild-type C57Bl/6 (WT) and SERT-knockout (SERTKO) mice were fasted then gavaged with D-xylose or boron-dipyrromethene (BODIPY) FL-C12 medium-chain fatty acid analog. Serum D-xylose and BODIPY concentrations were serially measured from blood drawn at 30 to 360 min post-gavage. Small intestine was harvested from both groups for comparison of morphometric parameters. Area under the curve of plotted graphs was calculated, and means were compared with Student's t-test to a significance of p < 0.05. RESULTS: Villus height and crypt depth were significantly greater in the middle and distal small intestine of SERTKO animals compared to WT. Overall absorption of D-xylose and BODIPY was greater in SERTKO animals compared to WT animals. Absorption of D-xylose was persistently elevated in SERTKO animals, while there was an initial delay in BODIPY absorption followed by a sustained and significantly greater absorption in SERTKO animals at 60-360 min after gavage. CONCLUSION: Potentiation of serotonin signaling in SERTKO mice results in small intestinal mucosal growth and enhanced carbohydrate and fat absorption in vivo. These functional increases support the concept of targeting the serotonin signaling system to augment intestinal adaptation in the setting of intestinal failure.

The Limited Utility of Routine Culture in Pediatric Pilonidal, Gluteal, and Perianal Abscesses.

BACKGROUND: Pilonidal, buttock, and perianal abscesses are common reasons for surgical consultation in the pediatric emergency department. Treatment typically includes a bedside incision and drainage, often followed by an abscess culture, and a course of oral antibiotics. We aimed to study the impact of culture data on changes in management and clinical outcomes. We hypothesized that management is unaffected by culture data, and therefore, fluid culture from pilonidal, buttock, and perianal abscesses in the pediatric population may represent an unnecessary laboratory test and cost. MATERIALS AND METHODS: A single institution's electronic medical record was searched between February 1, 2013 and August 1, 2017, identifying 249 pediatric patients meeting the inclusion criteria: age 0 to 18 y; diagnosis of pilonidal, buttock, or perianal abscess; bedside incision and drainage. Patients were divided into two different comparison groups for data analysis based on the presence or absence of culture and recurrence or no recurrence. RESULTS: Culture results directly altered management in only 5 patient encounters (2.7% of all cultured). When comparing groups by culture or no culture, no statistically significant difference in recurrence rate (P = 0.4) was noted. When comparing groups by recurrence versus no recurrence, we found no statistically significant difference between sex, resident type, vessel loop use, packing use, or antibiotic use (P > 0.05). CONCLUSIONS: We conclude that microbiological culture results are of limited utility in the management of pediatric pilonidal, buttock, and perianal abscesses as they do not appear to alter treatment, and omission of culture is not associated with failure of surgical management.

The Impact of Pediatric Surgical Specialty Meetings: A 5-year Analysis of Presented Abstracts.

BACKGROUND: Abstracts presented at the American Academy of Pediatrics Section on Surgery (AAP) and American Pediatric Surgical Association (APSA) meetings can be taken as a reasonable representation of academic activity in pediatric surgery. We sought to assess ongoing trends in pediatric surgical research by analyzing the scientific content of each association's yearly meeting. METHODS: Abstracts presented at AAP and APSA between 2009 and 2013 were identified from the final printed programs (n = 910). Video abstracts (n = 34) were excluded. Collected data included title, authors, classification (basic science/clinical), presentation type (podium/poster), and topic. Publication as a journal article was determined using the abstract title/authors in a PubMed search. Journal impact factors were recorded for each journal and a composite impact factor (CIF) was calculated by dividing the sum of impact factors by the published articles per meeting. RESULTS: Number of abstracts presented, percentage published, abstract classifications, and presentation type remained consistent over the study period. The AAP meetings accepted a higher percentage of clinical abstracts: AAP 72.3 ± 3.4% versus APSA 65.9 ± 1.3%. The five most popular topics at both meetings were oncology, congenital diaphragmatic hernia, necrotizing enterocolitis, trauma, and appendicitis. The publication rate for clinical and basic science abstracts did not vary significantly over the study period, whereas CIFs were higher for basic science publications nearly every year. The percentage of podium abstracts published was significantly greater than poster abstracts, but no statistical difference in CIF was seen between podium- and poster-associated publications. CONCLUSIONS: Abstracts accepted and presented at the two major pediatric surgical specialty meetings more commonly involve clinical studies with a trend away from basic science. Despite this, basic science abstracts tended to be published in higher impact journals. This study attempts to quantify the quality of pediatric surgical research and serves as a baseline for future comparison.

The 5-HT4 Receptor Agonist Prucalopride Stimulates Mucosal Growth and Enhances Carbohydrate Absorption in the Ileum of the Mouse.

BACKGROUND: Enteric serotonin may function as a mucosal growth factor. Previous work demonstrated increased crypt cell proliferation and intestinal mucosal surface area with potentiation of serotonin. While an indirect mechanism was postulated to explain these effects, the presence of 5-HT4 receptors on enterocytes raises the possibility of a direct action of serotonin. We hypothesized that a 5-HT4 specific agonist, prucalopride, would stimulate intestinal mucosal growth and enhance absorptive function in the murine small intestine. METHODS: Adult wild-type mice were treated parenterally with prucalopride for 14 days via surgically implanted osmotic pumps. In vivo D-xylose absorption was assessed by oral gavage and serum D-xylose measurements. On day 14, glucose absorption was assessed by instilling a glucose solution into isolated segments of small intestine. The bowel was harvested and examined for morphologic parameters and crypt cell proliferation. RESULTS: Villus height, crypt depth, and crypt proliferation were significantly increased in the distal small bowel of prucalopride-treated mice compared with control animals. Crypt depth was also increased in the proximal and middle small intestine in treated mice. There was no difference in D-xylose absorption throughout the study period; however, glucose absorption was significantly increased in the distal small intestine of prucalopride-treated mice. CONCLUSION: Parenteral administration of the 5-HT4 receptor specific agonist, prucalopride, results in morphologic and functional changes in the murine small intestine that are most prominent in the distal small bowel. While further studies are necessary to delineate the mechanism, it is plausible that the effects are mediated by 5-HT4 receptors on enterocytes.

Surgical modifications of the Kasai hepatoportoenterostomy minimize invasiveness without compromising short- and medium-term outcomes.

BACKGROUND: Biliary atresia (BA) causes progressive fibrosis and obliteration of the biliary tree, resulting in bile stasis and eventual liver dysfunction. It affects 1 in 10,000-18,000 infants, and if left untreated, universally leads to liver failure. The Kasai hepatoportoenterostomy (KPE) was developed as an effective surgical therapy for BA and can restore bile drainage into the intestine. Traditionally, the KPE procedure extra-corporealizes the liver to expose the portal plate. Here, we describe modifications to the procedure via a smaller incision in which the liver remains within the abdominal cavity and we compare the outcomes of this technique to previous institutional outcomes and to contemporary international series. MATERIALS AND METHODS: We identified all patients who underwent KPE for BA at a single institution between 1994 and 2012. Patient outcomes after the modified KPE performed from 2004 to 2012 were compared to data from infants who underwent the traditional KPE from 1994 to 2003. RESULTS: Ninety-nine patients were identified. Fifty-two were in the traditional KPE group and 47 in the modified KPE group. There was no difference in mean age at surgery. Median follow-up was 64 months (traditional KPE) and 46 months (modified KPE). The rate of native liver survival (39.1% vs 48.5%), overall survival (89.2% vs 97.8%), liver transplant occurring under one year of age (36.5% vs 40.4%) and median time to liver transplant (188 vs 172 days) were not statistically different between groups (p > 0.05 for all comparisons). The results of the modified KPE compared favorably to published outcomes. CONCLUSION: The described modifications to the KPE appear to yield equivalent outcomes when compared to the traditional KPE procedure and compare well with published outcomes in the literature. It is possible that the procedure described here results in less scarring and technically easier liver transplant procedures. LEVEL OF EVIDENCE: Level III.

Sacral Insufficiency Fractures are Common After High-dose Radiation for Sacral Chordomas Treated With or Without Surgery.

BACKGROUND: Surgery with high-dose radiation and high-dose radiation alone for sacral chordomas have shown promising local control rates. However, we have noted frequent sacral insufficiency fractures and perceived this rate to be higher than previously reported. QUESTIONS/PURPOSES: We wished (1) to characterize the incidence of sacral insufficiency fractures in patients with chordomas of the sacrum who received high-dose radiation, and (2) to determine whether patients treated with surgery plus high-dose radiation or high-dose radiation alone are more likely to experience a sacral fracture, and to compare time to fracture in these groups. METHODS: Sixty-two patients who received high-dose radiation for sacral chordomas with (n = 44) or without surgical resection (n = 18) between 1992 and 2013 were included in this retrospective study. At our institution, sacral chordomas generally are treated by preoperative radiotherapy, followed by en bloc resection, and postoperative radiotherapy. Radiation alone, with an intent to cure, is offered to patients who otherwise are not good surgical candidates or patients who elect radiotherapy based on tumor location and the anticipated morbidity after surgery (such as sexual, bowel, or bladder dysfunction). MRI and CT scans were evaluated for evidence of sacral insufficiency fractures. Complete followup was available at a minimum of 2 years (or until fracture or death) for all 18 patients who underwent radiation alone, whereas 14% (six of 44 patients) in the surgery plus radiation group (9% [three of 33] after high sacrectomy and 27% [three of 11] after low sacrectomy) were lost to followup before 2 years. RESULTS: Sacral insufficiency fractures occurred in 29 of the 62 patients (47%). A total of 25 of 33 patients (76%) with high sacrectomy had fractures develop compared with zero of 11 (0%) after low sacrectomy, and four of the 18 patients (22%) who had high-dose radiation alone (p < 0.001). The fracture rate was greater in the high sacrectomy group than in the low sacrectomy group (p < 0.001) and the radiation only group (p < 0.001). There was no difference with the numbers evaluated in fracture probability between patients in the low-sacrectomy group and those treated with radiation alone (p = 0.112). The fracture-free survival probability was 0.99 for the low sacrectomy group at all times as there were no insufficiency fractures in this group; the 1-year fracture-free survival probability was 0.53 (95% CI, 0.35-0.69) after high sacrectomy, 0.83 (95% CI, 0.57-0.94) after radiation alone; the 2-year fracture-free survival probability was 0.36 (95% CI, 0.19-0.52) after high sacrectomy and 0.77 (95% CI, 0.50-0.91) after radiation alone; and the 5-year fracture-free survival probability was 0.14 (95% CI, 0.04-0.30) after high sacrectomy and 0.77 (95% CI, 0.50-0.91) after radiation alone. CONCLUSIONS: Acknowledging the limitations of potential differences in baseline and followup among treatment groups in our study, we found that almost ½ of our patients experienced an insufficiency fracture. We found that the fracture rate was greater in the surgery group compared with the radiation alone group and that high sacrectomy accounted for all fractures in the surgery group. These findings can be used to inform patients and also support the need for further research to elucidate the influence of high-dose radiation on bone quality. LEVEL OF EVIDENCE: Level III, therapeutic study.

What factors are associated with a second opioid prescription after treatment of distal radius fractures with a volar locking plate?

PURPOSE: Knowledge of factors associated with patient's requests for a second opioid prescription after volar plate fixation of a fracture of the distal radius might inform better pain management protocols and encourage decreased and safer use of opioids. This study tested the primary null hypothesis that there is no difference in demographics, prior opioid prescriptions, injury characteristics, and psychological factors between patients that do and do not receive a second opioid prescription following treatment volar locking plate after distal radius fracture. PATIENTS AND METHODS: We used data on 206 patients enrolled in one of two prospective studies. Their mean age was 53 years ± SD 15, and 60 (30 %) were men. Forty-seven (23 %) patients received a second opioid prescription. We recorded additional demographics, AO fracture type, American Society for Anesthesiologists (ASA) classification, radiographic parameters at the time of injury prior to reduction and after surgery, and catastrophic thinking. RESULTS: Male sex (odds ratio [OR] 2.2, 95 % confidence interval [CI] 1.0-4.6, partial pseudo R (2) = 0.018, P = 0.044) and greater dorsal angulation of the articular surface on the lateral post injury radiograph (OR 0.98, 95 % CI 0.96 to 1.0, partial pseudo R (2) = 0.033, P = 0.040) were associated with a second opioid prescription after surgery (pseudo R (2) 0.12, P = 0.0071). CONCLUSIONS: One measure of fracture severity (dorsal displacement) was independently associated with a second opioid prescription, but alone it accounted for 3.3 % of the variation. Other factors such as the patient's expectation prior to surgery, in particular the realization that injury and surgery hurt, might be addressed in future research. LEVEL OF EVIDENCE: Prognostic II.

Efficient procurement of epithelial stem cells from human tissue specimens using a Rho-associated protein kinase inhibitor Y-27632.

The efficient culture of stem cells from epithelial tissues such as skin and corneas is important for both experimental studies and clinical applications of tissue engineering. We now demonstrate that treatment of human-skin-derived keratinocytes with a Rho-associated protein kinase inhibitor Y-27632 for the initial 6 days of primary culture can increase the number of keratinocytes that possess stem cell properties to form colonies during in vitro culture of freshly isolated cells and subsequent passage (50-fold). Further, we show that Y-27632 treatment can increase the total number of prostate epithelial cells derived from human prostate specimens. Therefore, the use of Y-27632 during primary cultures offers a simple and effective way to prepare a large number of epithelial stem cells from various human epithelial tissues.