Normative values for circulating intestinal fatty acid binding protein and calprotectin across gestational ages.

BACKGROUND: Necrotizing enterocolitis (NEC) is associated with significant morbidity and mortality. Serum biomarkers to aid diagnosis, such as intestinal fatty acid binding protein (IFABP) and calprotectin, are actively being investigated; however, the normative values of these markers among healthy premature and term infants remains unknown. We sought to identify normative values for the serum concentrations of IFABP and calprotectin across gestational (GA) and post-menstrual age. METHODS: We collected serum from infants (24-40 weeks GA) in the first week of life and at multiple time points in a sub-cohort of premature infants (24-29 weeks GA), excluding sepsis or known intestinal disease. IFABP and calprotectin were measured using ELISA. Groups were compared with descriptive statistics and mixed effects linear regression. RESULTS: One hundred twelve infants had specimens in the first week of life, and 19 premature infants had longitudinal specimens. IFABP concentration in the first week of life was low and did not differ across gestational ages. Longitudinally, IFABP increased 4% per day (P < 0.001). Calprotectin concentration in the first week of life was more variable. An inverse relationship between day of life and calprotectin level was found in the longitudinal cohort (P < 0.001). CONCLUSIONS: Serum IFABP and calprotectin fluctuate over time. Infants had low levels of IFABP during the first week of life, independent of gestational age, and levels increased longitudinally in premature infants. Calprotectin levels generally declined over time. Normative data for infants is necessary to establish meaningful cut-off levels for clinical use.

Who moved my fellow: changes to Accreditation Council for Graduate Medical Education fellowships in pediatric surgery and what may be yet to come.

PURPOSE OF REVIEW: Over the past 15 years, the Accreditation Council for Graduate Medical Education (ACGME) has significantly altered the regulatory framework governing fellowship training in pediatric surgery. The daily experiences of pediatric surgical trainees have been impacted by these changes, but training program directors and faculty have not developed a consistent approach to managing this shift. This review highlights the changes, which have occurred, analyzes the current state of fellowship training, and proposes potential strategies for management. RECENT FINDINGS: The implementation of work hour restrictions, increased supervision requirements, the milestone evaluation program and most recently, enforcement of required critical care experience, have caused significant changes in the curriculum. Pediatric surgical trainees record more total cases, and more minimally invasive surgical (MIS) cases, in particular, than ever before. A subset of this increase may result from trainees performing cases previously assigned to general surgery residents. Teaching cases performed by fellows have decreased. Although the relationship between these shifts in training experience and the didactic curriculum is not clear, we also note that the Pediatric Surgery Certifying Examination failure rate has increased, approaching 20% in recent years. SUMMARY: It is unclear whether the changes in Pediatric Surgery training programs have been effective, or (conversely) have led to unintended consequences. Paradigm shifts in our training model may be required to address the changes in surgical education and skill acquisition, so that well tolerated, competent and skillful pediatric surgeons continue to enter the workforce.

Postoperative Enteral Nutrition Guidelines Reduce the Risk of Intestinal Failure-Associated Liver Disease in Surgical Infants.

OBJECTIVE: To assess the effectiveness of postoperative feeding guidelines in reducing the incidence and severity of intestinal failure-associated liver disease (IFALD) among infants. STUDY DESIGN: Two cohorts of infants <6 months old undergoing intestinal surgery were compared: preguideline (retrospective data from 2007 to 2013; n = 83) and postguideline (prospective data from 2013 to 2016; n = 81). The guidelines included greater initial enteral nutrition volumes of 20 mL/kg/d and daily feeding advancement if tolerated. The primary outcomes were incidence of IFALD (peak direct bilirubin [DB] >2 mg/dL) and severity (DB >5 mg/dL for moderate-severe). Multiple logistic regression was used to determine the odds of developing IFALD. Other outcomes were time to reach 50% and 100% goal calories from enteral nutrition and the incidence of necrotizing enterocolitis after feeding. RESULTS: The incidence of IFALD decreased from 71% to 51% (P = .031), and median peak DB decreased from 5.7 to 2.4 mg/dL (P = .001). After adjusting for diagnosis and prematurity, the odds of developing IFALD of any severity were reduced by 60% (OR 0.40, 95% CI 0.20-0.85), and the odds of developing moderate-to-severe IFALD were reduced by 72% (OR 0.28, 95% CI 0.13-0.58) with guideline use. Time to reach 50% enteral nutrition decreased from a median of 10 to 6 days (P = .020) and time to reach 100% enteral nutrition decreased from 35 to 21 days (P = .035) with guideline use. The incidence of necrotizing enterocolitis after initiating enteral nutrition did not change (5% vs 9%, P = .346). CONCLUSIONS: Implementation of feeding guidelines reduced time to reach feeding goals, significantly reducing IFALD incidence and severity.

Analysis of risk factors for morbidity in children undergoing the Kasai procedure for biliary atresia.

OBJECTIVE: To evaluate the perioperative risk factors for 30-day complications of the Kasai procedure in a large, cross-institutional, modern dataset. STUDY DESIGN: The 2012-2015 National Surgical Quality Improvement Program Pediatric database was used to identify patients undergoing the Kasai procedure. Patients' characteristics were compared by perioperative blood transfusions and 30-day outcomes, including complications, reoperations, and readmissions. Multivariable logistic regression was used to identify risk factors predictive of outcomes. Propensity matching was performed for perioperative blood transfusions to evaluate its effect on outcomes. RESULTS: 190 children were included with average age of 62 days. Major cardiac risk factors were seen in 6.3%. Perioperative blood transfusions occurred in 32.1%. The 30-day post-operative complication rate was 15.8%, reoperation 6.8%, and readmission 15.3%. After multivariate analysis, perioperative blood transfusions (OR 3.94; p < 0.01) and major cardiac risk factors (OR 7.82; p < 0.01) were found to increase the risk of a complication. Perioperative blood transfusion (OR 4.71; p = 0.01) was associated with an increased risk of reoperation. Readmission risk was increased by prematurity (OR 3.88; p = 0.04) and 30-day complication event (OR 4.09; p = 0.01). After propensity matching, perioperative blood transfusion was associated with an increase in complications (p < 0.01) and length of stay (p < 0.01). CONCLUSION: Major cardiac risk factors and perioperative blood transfusions increase the risk of post-operative complications in children undergoing the Kasai procedure. Further research is warranted in the perioperative use of blood transfusions in this population. LEVEL OF EVIDENCE: IV.

Artificial Intelligence vs. Doctors: Diagnosing Necrotizing Enterocolitis on Abdominal Radiographs.

BACKGROUND: Radiographic diagnosis of necrotizing enterocolitis (NEC) is challenging. Deep learning models may improve accuracy by recognizing subtle imaging patterns. We hypothesized it would perform with comparable accuracy to that of senior surgical residents. METHODS: This cohort study compiled 494 anteroposterior neonatal abdominal radiographs (214 images NEC, 280 other) and randomly divided them into training, validation, and test sets. Transfer learning was utilized to fine-tune a ResNet-50 deep convolutional neural network (DCNN) pre-trained on ImageNet. Gradient-weighted Class Activation Mapping (Grad-CAM) heatmaps visualized image regions of greatest relevance to the pretrained neural network. Senior surgery residents at a single institution examined the test set. Resident and DCNN ability to identify pneumatosis on radiographic images were measured via area under the receiver operating curves (AUROC) and compared using DeLong's method. RESULTS: The pretrained neural network achieved AUROC of 0.918 (95% CI, 0.837-0.978) with an accuracy of 87.8% with five false negative and one false positive prediction. Heatmaps confirmed appropriate image region emphasis by the pretrained neural network. Senior surgical residents had a median area under the receiver operating curve of 0.896, ranging from 0.778 (95% CI 0.615-0.941) to 0.991 (95% CI 0.971-0.999) with zero to five false negatives and one to eleven false positive predictions. The deep convolutional neural network performed comparably to each surgical resident's performance (p > 0.05 for all comparisons). CONCLUSIONS: A deep convolutional neural network trained to recognize pneumatosis can quickly and accurately assist clinicians in promptly identifying NEC in clinical practice. LEVEL OF EVIDENCE: III (study type: Study of Diagnostic Test, study of nonconsecutive patients without a universally applied "gold standard").

The First Two Years of the Association of Pediatric Surgery Training Program Directors (APSTPD) Transition to Fellowship Course: Lessons Learned and Future Directions.

OBJECTIVE: The first transition to fellowship course for incoming pediatric surgery fellows was held in the US in 2018 and the second in 2019. The course aimed to facilitate a successful transition in to fellowship by introduction of the professional, patient care, and technical aspects unique to pediatric surgery training. The purpose of this study was to evaluate the feasibility and effectiveness of the first two years of this course in the US and discuss subsequent evolution of this endeavor. DESIGN: This is a descriptive and qualitative analysis of two years' experience with the Association of Pediatric Surgery Training Program Directors' (APSTPD) Transition to Fellowship course. Course development and curriculum, including clinical knowledge, soft skills, and hands-on skills labs, are presented. Participating incoming fellows completed multiple choice, boards-style pre- and post-tests. Scores were compared to determine if knowledge was effectively transferred. Participants also completed post-course evaluations and subsequent 3- or 12-month surveys inquiring on the lasting impact of the course on their transition into fellowship. Standard univariate statistics were used to present results. SETTING: The first APSTPD Transition to Fellowship course was held at the Johns Hopkins Hospital in Baltimore, Maryland in 2018, and the second course was held at the Oregon Health and Science University in Portland, Oregon in 2019. PARTICIPANTS: All fellows entering ACGME-certified Pediatric Surgery fellowships in the United States were invited to participate. Twenty fellows accepted and attended in 2018, and fourteen fellows participated in 2019. RESULTS: There were 34 incoming pediatric surgery fellow participants over 2 years. Faculty represented more than 10 institutions each year. Pre- and post-test scores were similar between years, with a significant improvement of scores after completion of the course (67±10% vs 79±8%, p < 0.001). Feedback from participants was overwhelmingly positive, with skills labs being attendees' favorite component. When asked about usefulness of individual course sessions, more attendees found clinical sessions more useful than soft skills (93% vs 73%, p = 0.011). Almost all (90%) of participants reported the course met its stated purpose and would recommend the course to future fellows. This was further reflected on 3 and 12 month follow up surveys wherein 85% stated they found the course helpful during the first few months of fellowship and 90% would still recommend it. CONCLUSIONS: A transition to fellowship course in the US for incoming pediatric surgery fellows is logistically feasible, effective in transfer of knowledge, and highly regarded among attendees. Feedback from each course has been used to improve the subsequent courses, ensuring that it remains a valuable addition to pediatric surgical training in the US.

Esophageal Surveillance Practices in Esophageal Atresia Patients: A Survey by the Eastern Pediatric Surgery Network.

INTRODUCTION: Endoscopic surveillance guidelines for patients with repaired esophageal atresia (EA) rely primarily on expert opinion. Prior to embarking on a prospective EA surveillance registry, we sought to understand EA surveillance practices within the Eastern Pediatric Surgery Network (EPSN). METHODS: An anonymous, 23-question Qualtrics survey was emailed to 181 physicians (surgeons and gastroenterologists) at 19 member institutions. Likert scale questions gauged agreement with international EA surveillance guideline-derived statements. Multiple-choice questions assessed individual and institutional practices. RESULTS: The response rate was 77%. Most respondents (80%) strongly agree or agree that EA surveillance endoscopy should follow a set schedule, while only 36% claimed to perform routine upper GI endoscopy regardless of symptoms. Many institutions (77%) have an aerodigestive clinic, even if some lack a multi-disciplinary EA team. Most physicians (72%) expressed strong interest in helping develop evidence-based guidelines. CONCLUSIONS: Our survey reveals physician agreement with current guidelines but weak adherence. Surveillance methods vary greatly, underscoring the lack of evidence-based data to guide EA care. Aerodigestive clinics may help implement surveillance schedules. Respondents support evidence-based protocols, which bodes well for care standardization. Results will inform the first multi-institutional EA databases in the United States (US), which will be essential for evidence-based care. LEVEL OF EVIDENCE: This is a prognosis study with level 4 evidence.

Streptococcus viridans tubo-ovarian abscess in an adolescent virgin.

A tubo-ovarian abscess (TOA) is a common complication of pelvic inflammatory disease in premenopausal women; however, in virginal females, TOAs are an exceedingly rare occurrence. Within this rare subset of patients, there is almost always an underlying condition, such as vaginal voiding, or a concomitant disease process. A virginal adolescent female with no prior medical history presented with a large pelvic mass which proved to be a TOA. An exploratory laparotomy was eventually required to establish the diagnosis. Open drainage and antibiotic therapy successfully treated the patient. With only the organism, Streptococcus viridians, isolated in her cultures, an etiology of direct ascension from the lower genitourinary tract is implicated. We believe this to be the youngest case of a TOA occurring in a virginal adolescent female without a predisposing condition. A TOA should be considered in the differential diagnosis of pelvic masses in previously healthy pediatric patients regardless of their sexual activity.

Pediatric surgery milestones 2.0: A primer.

More than twenty years ago, the Accreditation Council for Graduate Medical Education and the American Board of Medical Specialties began the conversion of graduate medical education from a structure- and process-based model to a competency-based framework. The educational outcomes assessment tool, known as the Milestones, was introduced in 2013 for seven specialties and by 2015 for the remaining specialties, including pediatric surgery. Designed to be an iterative process with improvements over time based on feedback and evidence-based literature, the Milestones started the evolution from 1.0 to 2.0 in 2016. The formation of Pediatric Surgery Milestones 2.0 began in 2019 and was finalized in 2021 for implementation in the 2022-2023 academic year. Milestones 2.0 are fewer in number and are stated in more straightforward language. It incorporated the harmonized milestones, subcompetencies for non-patient care and non-medical knowledge that are consistent across all medical and surgical specialties. There is a new Supplemental Guide that lists examples, references and links to other assessment tools and resources for each subcompetency. Milestones 2.0 represents a continuous process of feedback, literature review and revision with goals of improving patient care and maintaining public trust in graduate medical education's ability to self-regulate. LEVEL OF EVIDENCE: V.

Employment search, initial employment experience, and career preferences of recent pediatric surgical fellowship graduates: An APSA survey, part of the right child/right surgeon initiative.

BACKGROUND: APSA's Right Child/Right Surgeon Initiative addresses issues concerning patient access to appropriate pediatric surgical care and workforce distribution. The APSA Workforce Committee sought to understand the experiences and motivations of recent graduates of Pediatric Surgery Training Programs entering the workforce. METHODS: Using APSA membership databases, we identified members who completed fellowship training from 2010 to 2019. An online survey was created using Survey Monkey, and invitations to participate were sent via email. RESULTS: 144 of 447 invited participants responded (32% response rate). 91% of respondents participated in dedicated research prior to fellowship, but only 64% perform research during their employment. 23% completed an additional clinical fellowship, but only 54% currently practice within the second field. When asked to identify the top three factors used to choose a position, the most common responses were "location or geography" (71%), "available mentorship" (53%), and "compensation and benefits" (37%). Describing their first position, 77% reported working in an academic institution, 78% reported working in a metropolitan/urban area, and 55% reported working in a free-standing children's hospital. 94% participate in General Surgery resident education, and 49% are faculty within a Pediatric Surgery fellowship. Overall, 92% of respondents were able to find the type of employment position that they had wanted. CONCLUSION: In our survey the overwhelming majority of young pediatric surgeons found the type of job they desired. Most report beginning their practice in more populated, urban areas within academic institutions. Geographic location and work environment played heavily into their employment decisions. These preferences could contribute to continued disparity in access to pediatric surgeons between urban and rural America and to dilution of experience for urban surgeons. Possible solutions include alternative incentive programs for employment in less populated areas or new training models for general surgeons in rural areas to train in fundamentals of Pediatric Surgery.

The Right Child/Right Surgeon initiative: A position statement on pediatric surgical training, sub-specialization, and continuous certification from the American Pediatric Surgical Association.

The past 50 years have witnessed profound changes in the specialty of pediatric surgery in North America. There has been a marked increase in the number of both pediatric surgical training programs and practicing pediatric general and thoracic surgeons. Despite this trend, the population of children in the United States and the birth rate have recently remained relatively flat. Some pediatric surgeons have become "super specialists", concentrating their practices in oncology or colorectal surgery. This has the potential to result in a dilution of experience for both pediatric surgical trainees and practicing pediatric surgeons, thus limiting their ability to acquire and maintain expertise, respectively. Coincident with this, there has been a relative paradigm shift in recognition that "quality of life" is based more on maintaining a creative balance in lifestyle and is not "all about work". There has been a parallel growth in the number of practicing pediatric general and thoracic surgeons in urban settings, but we have not appreciated as much growth in rural and underserved areas, where access to pediatric surgical care remains limited and fewer pediatric general and thoracic surgeons practice. This is a complex issue, as some underserved areas are economically depressed and geographically sparse, but others are just underserved with adult providers taking care of children in settings that are often under resourced for pediatric surgical care. This problem may extend beyond the boundaries of pediatric general and thoracic surgery to other specialties. As the premier association representing all pediatric surgeons in the United States, the American Pediatric Surgical Association (APSA) has concluded that the quality of pediatric surgical care will likely decline should the status quo be allowed to continue. Therefore, APSA has initiated a Right Child/Right Surgeon initiative to consider these issues and propose some potential solutions. What follows is a brief statement of intent.

A Central Role for Lipocalin-2 in the Adaptation to Short-Bowel Syndrome Through Down-Regulation of IL22 in Mice.

BACKGROUND & AIMS: In short-bowel syndrome (SBS), inadequate intestinal adaptation is responsible for the majority of complications, including sepsis, liver failure, and death. In this study, we sought to further delineate the adaptive response to identify potential therapeutic targets. METHODS: We performed a 75% small-bowel resection (SBR) or sham operation on C57Bl/6J wild-type (WT), lipocalin-2 (LCN2)-/-, and interleukin 22 (IL22)-/- mice. Exogenous IL22 was administered to SBR WT mice. Cecal fecal matter from SBR WT and SBR LCN2-/- mice were transplanted into germ-free mice. Intestinal permeability, inflammation, proliferation, and the microbiome were evaluated 1 week after surgery. CD4+IL22+ laminal propria lymphocytes were sorted by flow cytometry. Naïve T cells were polarized to T-helper cells with or without LCN2. RESULTS: A 75% SBR in a mouse re-creates the increased intestinal permeability, enterocyte proliferation, and intestinal dysbiosis seen in SBS. LCN2 expression increases after 75% SBR, and this increase can be abrogated with broad-spectrum antibiotic treatment. LCN2-/- mice have less intestinal inflammation, increased IL22 expression, and greater adaptation as evidenced by less intestinal permeability, increased carbohydrate enzyme expression, less weight loss, and less dysbiosis after 75% SBR than WT mice. The proinflammatory and anti-adaptive effects of LCN2 can be transferred to germ-free mice via a fecal transplant. Administration of exogenous IL22 improves adaptation and restores the normal microbiome after 75% SBR in WT mice. CONCLUSIONS: LCN2 promotes inflammation and slows intestinal adaptation through changes in the microbiome and IL22 inhibition in a mouse SBS model. Strategies to reduce LCN2 may offer novel therapeutic approaches to enhance adaptation in SBS.

Pediatric Femoral Arterial Cannulations in Extracorporeal Membrane Oxygenation: A Review and Strategies for Optimization.

Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) is a treatment strategy for pediatric patients with cardiopulmonary failure. Femoral cannulation is a commonly used technique for obtaining central access in children and adolescents despite high rates of vascular complications. Ischemic limb complications remain one of the most common problems facing survivors of femoral VA ECMO. Our aim is to review the literature on femoral cannulation in children and to present a review of techniques for femoral cannula placement, decannulation, and arterial repair to help minimize and ameliorate complications related to cannulation. We performed a literature review for pediatric ECMO cannulation, complications, and femoral artery repair in pediatric patients. We focused on the management of arterial and ischemia-related complications during and after ECMO support via femoral cannulation. Vascular complications are not infrequent for patients requiring ECMO support via femoral cannulation. As such, judicious distal perfusion monitoring as well as augmentation of distal flow are important strategies during mechanical support. The use of distal perfusion catheters can be used to minimize the risk of limb ischemia. As femoral cannulation grows more popular in pediatric patients, strategies for arterial repair are essential to ensure extremity perfusion upon decannulation.

Minimally invasive repair of pectus excavatum: Analysis of the NSQIP database and the use of thoracoscopy.

BACKGROUND: The minimally invasive repair of pectus excavatum (MIRPE) has been widely accepted and has become a viable alternative to the open Ravitch technique. MIRPE has evolved over time with some advocating that a safe repair can be accomplished without direct visualization utilizing thoracoscopy. The MIRPE with and without a thoracoscopic approach has not been previously analyzed from a nationwide database to determine differences in safety and short-term outcomes. METHODS: The American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-P) 2012-2015 database was used in identifying patients that had MIRPE using Current Procedural Terminology (CPT) codes and ICD-9CM/ICD-10CM postoperative diagnosis codes. Outcomes of interest were readmissions, reoperations, complications, cardiothoracic injury, operative time, and duration of hospital stay after surgery for MIRPE with and without thoracoscopy. Descriptive statistics, simple and multivariable logistic regressions, Fisher's exact, and Wilcoxon rank sum test were used to determine any differences in 30-day postoperative outcomes. RESULTS: There were 1569 MIRPE cases included. 15.9% (N=249) of MIRPE were done without thoracoscopy. There were no significant differences with the use of thoracoscopy compared to without thoracoscopy in the rate of readmissions (2.5 vs 4.8%; p=0.06), reoperations (1.4 vs 2.0%; p=0.57), postoperative complications (2.6% vs 3.2%; p=0.52), and cardiothoracic injuries (0.2% vs 0.0%; p=1.00). Unadjusted odds ratios (ORs) for readmission and reoperation comparing MIRPE with thoracoscopy to MIRPE without thoracoscopy were 0.51 (p<0.05) and 0.71 (p=0.50), respectively. Adjusted ORs were 0.49 (p=0.04) and 0.71 (p=0.50), respectively. There were no reported deaths, but two cardiothoracic injuries were recorded in the group with thoracoscopy. MIRPE with thoracoscopy was associated with longer operative time (mean 13.0min; p=0.00) and longer hospital stay (mean 0.37days; p<0.01) compared to MIRPE without thoracoscopy. No data were available for the severity of the pectus defect. CONCLUSION: MIRPE has a low adverse event rate with no difference in reoperations, postoperative complications, and cardiothoracic injuries with or without the use of thoracoscopy. There may be a higher rate of readmissions in the nonthoracoscopic group. While the technique used remains the surgeon's decision, the use of thoracoscopy may be unnecessary and is at an added cost. TYPE OF STUDY: Treatment study (retrospective comparative study). LEVEL OF EVIDENCE: Level III.

Testicular juvenile granulosa cell tumor in a newborn: case report and review of the literature.

Juvenile granulosa cell tumor of the testis of neonates and infants is an uncommon lesion frequently associated with abnormal sex chromosome and ambiguous genitalia. This report describes a juvenile granulosa cell tumor arising in the testis of a neonate. Chromosome analysis of the tumor showed a normal male karyotype 46 XY. Histopathology and immunohistochemical studies revealed the occurrence of 2 well-differentiated epithelial-like and smooth muscle-like components in the neoplasm. The morphologic clues leading to the correct diagnosis of juvenile granulosa cell tumor and the possible histogenesis are briefly discussed.

The severity of cholestatic injury is modulated by the genetic background.

Common bile duct ligation (CBDL) compromises the hepatic reticuloendothelial system by impairing the clearing of endotoxin and triggering an overwhelming inflammatory response. The response to endotoxin at the level of cytokine release and subsequent mortality depends on the genetic background in experimental mouse models. We hypothesized that the genetic make-up modulates the inflammatory responses after CBDL. The CBD was ligated in male A/J and B6 mice (8 weeks old). At 7 days post-CBDL, the presence of ascites was observed in 80% of B6 mice but in none of the A/J mice (P < 0.001). B6 mice showed higher mortality than A/J mice (P < 0.05). Both strains had marked cholestatic injury documented histologically. Liver chemistries were markedly elevated in both strains after injury. Plasma levels of the anti-inflammatory cytokine IL-10 were significantly higher in A/J than B6 mice at the 4- and 12-h time points (P < 0.05), whereas proinflammatory cytokine TNF-alpha levels were significantly higher in B6 than A/J mice at 2 h (P < 0.05). Both strains displayed activation of NF-kappaB after CBDL. In conclusion, the contrasting response observed after CBDL between A/J and B6 mice is largely attributable to genetic differences. Survival after CBDL was correlated with an increase in anti-inflammatory cytokines.

Patch Testing for Metal Allergy With Manufacturer-Supplied Materials Before Nuss Bar Insertion.

INTRODUCTION: The increasing use of metal implantable devices has raised awareness of nickel allergy. Preoperative patch testing for patients with pectus excavatum (PE) with a known metal allergy or history of atopy is an accepted practice before the Nuss procedure. The Nuss bar manufacturer offers a metal disc for preoperative testing for metal sensitivities. However, the efficacy of this disc is not well understood. OBJECTIVE: The purpose of this study was to determine the sensitivity of the metal disc in detecting nickel allergy compared with that of standard patch testing. METHODS: Two PE patients were referred for preoperative patch testing with the metal disc to screen for metal allergy before the Nuss procedure. Based on our initial findings, 7 patients without PE scheduled for patch testing for the evaluation of chronic dermatitis were additionally tested with the metal disc if they were found to have risk factors for nickel allergy. All patch testing was performed according to set standards. CONCLUSIONS: The metal disc may not be adequately sensitive to determine nickel allergy before the Nuss procedure. Patch testing alone with standard formulations of nickel sulfate in petrolatum may be more sensitive in diagnosing nickel allergy.

Gut microbiota, tight junction protein expression, intestinal resistance, bacterial translocation and mortality following cholestasis depend on the genetic background of the host.

Failure of the intestinal barrier is a characteristic feature of cholestasis. We have previously observed higher mortality in C57BL/6J compared with A/J mice following common bile duct ligation (CBDL). We hypothesized the alteration in gut barrier function following cholestasis would vary by genetic background. Following one week of CBDL, jejunal TEER was significantly reduced in each ligated mouse compared with their sham counterparts; moreover, jejunal TEER was significantly lower in both sham and ligated C57BL/6J compared with sham and ligated A/J mice, respectively. Bacterial translocation to mesenteric lymph nodes was significantly increased in C57BL/6J mice vs. A/J mice. Four of 15 C57BL/6J mice were bacteremic; whereas, none of the 17 A/J mice were. Jejunal IFN-γ mRNA expression was significantly elevated in C57BL/6J compared with A/J mice. Western blot analysis demonstrated a significant decrease in occludin protein expression in C57BL/6J compared with A/J mice following both sham operation and CBDL. Only C57BL/6J mice demonstrated a marked decrease in ZO-1 protein expression following CBDL compared with shams. Pyrosequencing of the 16S rRNA gene in fecal samples showed a dysbiosis only in C57BL/6J mice following CBDL when compared with shams. This study provides evidence of strain differences in gut microbiota, tight junction protein expression, intestinal resistance and bacterial translocation which supports the notion of a genetic predisposition to exaggerated injury following cholestasis.

CANDIDATE GENES FOR LIMITING CHOLESTATIC INTESTINAL INJURY IDENTIFIED BY GENE EXPRESSION PROFILING.

The lack of bile flow from the liver into the intestine can have devastating complications including hepatic failure, sepsis and even death. This pathologic condition known as cholestasis can result from etiologies as diverse as total parenteral nutrition (TPN), hepatitis and pancreatic cancer. The intestinal injury associated with cholestasis has been shown to result in decreased intestinal resistance, increased bacterial translocation and increased endotoxemia. Anecdotal clinical evidence suggests a genetic predisposition to exaggerated injury. Recent animal research on two different strains of inbred mice demonstrating different rates of bacterial translocation with different mortality rates supports this premise. In this study, a microarray analysis of intestinal tissue following common bile duct ligation (CBDL) performed under general anesthesia on these same two strains of inbred mice was done with the goal of identifying the potential molecular mechanistic pathways responsible. Over 500 genes were increased more than 2.0 fold following CBDL. The most promising candidate genes included MUPs, Serpina1a and LCN-2. RT-PCR validated the microarray results for these candidate genes. In an in vitro experiment using differentiated intestinal epithelial cells, inhibition of MUP-1 by siRNA resulted in increased intestinal epithelial cell permeability. Diverse novel mechanisms involving the growth hormone pathway, the acute phase response and the innate immune response are thus potential avenues for limiting cholestatic intestinal injury. Changes in gene expression were at times found to be not only due to the CBDL but also due to the murine strain. Should further studies in cholestatic patients demonstrate inter-individual variability similar to what we have shown in mice, then a "personalized medicine" approach to cholestatic patients may become possible.