Effect of Early vs Late Inguinal Hernia Repair on Serious Adverse Event Rates in Preterm Infants: A Randomized Clinical Trial.

Importance: Inguinal hernia repair in preterm infants is common and is associated with considerable morbidity. Whether the inguinal hernia should be repaired prior to or after discharge from the neonatal intensive care unit is controversial. Objective: To evaluate the safety of early vs late surgical repair for preterm infants with an inguinal hernia. Design, Setting, and Participants: A multicenter randomized clinical trial including preterm infants with inguinal hernia diagnosed during initial hospitalization was conducted between September 2013 and April 2021 at 39 US hospitals. Follow-up was completed on January 3, 2023. Interventions: In the early repair strategy, infants underwent inguinal hernia repair before neonatal intensive care unit discharge. In the late repair strategy, hernia repair was planned after discharge from the neonatal intensive care unit and when the infants were older than 55 weeks' postmenstrual age. Main Outcomes and Measures: The primary outcome was occurrence of any prespecified serious adverse event during the 10-month observation period (determined by a blinded adjudication committee). The secondary outcomes included the total number of days in the hospital during the 10-month observation period. Results: Among the 338 randomized infants (172 in the early repair group and 166 in the late repair group), 320 underwent operative repair (86% were male; 2% were Asian, 30% were Black, 16% were Hispanic, 59% were White, and race and ethnicity were unknown in 9% and 4%, respectively; the mean gestational age at birth was 26.6 weeks [SD, 2.8 weeks]; the mean postnatal age at enrollment was 12 weeks [SD, 5 weeks]). Among 308 infants (91%) with complete data (159 in the early repair group and 149 in the late repair group), 44 (28%) in the early repair group vs 27 (18%) in the late repair group had at least 1 serious adverse event (risk difference, -7.9% [95% credible interval, -16.9% to 0%]; 97% bayesian posterior probability of benefit with late repair). The median number of days in the hospital during the 10-month observation period was 19.0 days (IQR, 9.8 to 35.0 days) in the early repair group vs 16.0 days (IQR, 7.0 to 38.0 days) in the late repair group (82% posterior probability of benefit with late repair). In the prespecified subgroup analyses, the probability that late repair reduced the number of infants with at least 1 serious adverse event was higher in infants with a gestational age younger than 28 weeks and in those with bronchopulmonary dysplasia (99% probability of benefit in each subgroup). Conclusions and Relevance: Among preterm infants with inguinal hernia, the late repair strategy resulted in fewer infants having at least 1 serious adverse event. These findings support delaying inguinal hernia repair until after initial discharge from the neonatal intensive care unit. Trial Registration: ClinicalTrials.gov Identifier: NCT01678638.

A Pediatric Level III Trauma Center Experience With Dog Bite Injuries.

Dog bite injuries often present to Emergency Departments (ED), and between 2001 and 2003, approximately 4.5 million adults and children were injured. Injuries may range from puncture wounds to deep tissue lacerations or avulsions. Deaths have been described. Our objective was to describe dog bite injuries, the overall location of injuries, and need for vaccination among children who presented to a Pediatric ED designated as a level III trauma center with a robust facial surgical infrastructure. This was a 6-year retrospective study. Charts were identified by International Classification of Diseases, Tenth Revision (ICD-10) codes for lacerations or injuries secondary to animal bites and accessing the hospital's trauma database. Variables abstracted were age, sex, type of injury, location, need for antibiotics, immunization states and requirement of tetanus or rabies vaccine, disposition from ED to the operating room, home, or any in-patient unit. We excluded children older than 17 years of age and children who had a post-bite injury infection or injury not initially managed in our facility or medical system. The final cohort consisted of 152 children. The median age was 52 months and age ranged from 2 to 215 months. Children with a single bite injury were older when compared with those with numerous injuries, 81 and 62 months of age, respectively. Among young children, 75% of injuries occurred above the neck and 15.1% were managed in the operating room. Twenty-four percent of children required either a tetanus or rabies vaccination. Most dog bite injuries occurred to facial structures. Comprehensive care of dog victims included awareness of both dog and injured child vaccination status.

The Pediatric Emergency Department Nurse and Gastrostomy Tube Replacement: How Safe Is it?

AIM: To review the outcomes of a nurse-only guideline for replacement of gastrostomy tubes (g-tubes) in a pediatric emergency department (ED) and compare rates of success, failure, length of stay (LOS), and return visits with that of ED physicians. DESIGN: Nursing g-tube guidelines, created by a nurse educator and nursing council, were instigated on January 31, 2018. Variables examined included LOS, age at visit, return visit within 72 hours, reason for replacement, and any postplacement complications. REVIEW METHODS: Data of g-tube placement by nurses and physicians were compared using t test or χ 2 analysis (IBM-SPSS version 20, New Orchard Road, Armonk, NY). The institutional review board determined the study to be exempt from human subjects. The STROBE checklist was used and completed accordingly. DATA SOURCES: Chart abstraction and data were collected from January 1, 2011 through April 13, 2020, and medical records were obtained using International Classification of Diseases, Tenth Revision (ICD-10) codes for g-tubes: Z93.1, K94.23. RESULTS: A total of 110 patients were included in our study. Fifty-eight underwent nursing-only replacements; 52 were replaced by physicians. Nurse replacement success rate was 98.3% with an average stay of 22 minutes. Physician success rate was 100% with an average stay of 86 minutes. The difference between nursing and physician LOS was 64.6 minutes. No patient in either group experienced postreplacement complications. CONCLUSIONS: The initiation of nurse-only management of dislodged g-tubes was successful, safe, and had a shorter LOS when compared with physicians in the pediatric ED. IMPACT: Our study determined the implications of nurse-only replacement of g-tubes in a pediatric ED. We found that nurses replacing g-tubes was equally safe and effective as physician counterparts. In addition, we found that it significantly reduced the LOS for patients, which has consequences on patient satisfaction and billing. PATIENT/PUBLIC CONTRIBUTION: Nursing staff were trained in g-tube replacement using guidelines created by a nurse educator and nursing council. Patients either had their dislodged g-tubes replaced by the trained nurse or a physician and comparisons on the outcomes were made. Patients were aware of the study and consented to have their medical records accessed to make the data comparisons. RELEVANCE TO CLINICAL PRACTICE: With more than 189,000 children in the United States relying on g-tubes, nursing staff will inevitably be involved in the care of patients with such a device. In addition, as pediatric EDs continue to develop longer and longer waiting times, we must learn how to better use our nursing staff for procedures within their scope and minimize LOS. Our research demonstrates the safety, feasibility, and general benefits of having the pediatric nursing staff replace g-tubes in the ED, and it is hoped that this will lead to beneficial policy changes. WHAT DOES THIS ARTICLE CONTRIBUTE TO THE WIDER GLOBAL COMMUNITY: - Demonstrates the safety and effectiveness of nurse-only g-tube replacement- Reports on the statistically significant difference in LOS between physician and nurse replacement of g-tubes in a pediatric ED- Has the ability to lead to policy change in the pediatric ED that will allow for greater patient satisfaction and decrease patient cost.

Analysis of pediatric sternal fractures using the Kid's Inpatient Database (KID).

PURPOSE: This study aims to determine if sternal fracture is a predictor of discharge requiring additional care and mortality. METHODS: Blunt pediatric trauma admissions (<18 years) in the Kid's Inpatient Database (2016) were included in analysis. Weighted incidence of sternal fracture was calculated and adjusted for using survey weight, sampling clusters, and stratum. Regression analysis was used to identify factors associated with poor outcomes. RESULTS: Annual incidence of sternal fracture in the pediatric blunt trauma population was 0.43 per 100,000. Of 50,076 patients identified, 236 had sternal fractures. The sternal fracture patients were older (median 16 vs 10 years, P < 0.001) and motor vehicle accident was more frequently the mechanism of injury (78% vs 24%, P < 0.001). Common injuries associated with sternal fracture included clavicle fracture (43%), abdominal organ injury (28%), spinal fracture (47%), lung injury (65%), and rib fracture (47%).  Sternal fracture patients were more frequently discharged to receive additional care (22% vs 5%, P < 0.001) and to die of their injuries (3.8% vs 0.9%, P < 0.001). When adjusting for other factors associated with poor outcomes, sternal fracture was not an independent predictor of mortality or discharge to care. CONCLUSIONS: Sternal fracture is a severe injury in the pediatric population, but it is not independently associated with need for a higher level of care after discharge or mortality.

Fetal inflammation induces acute immune tolerance in the neonatal rat hippocampus.

BACKGROUND: Infants born preterm due to chorioamnionitis are frequently affected by a fetal inflammatory response syndrome (FIRS) and then by subsequent postnatal infections. FIRS and postnatal systemic inflammatory events independently contribute to poor neurocognitive outcomes of preterm infants. Developmental integrity of the hippocampus is crucial for intact neurocognitive outcomes in preterms and hippocampally dependent behaviors are particularly vulnerable to preterm systemic inflammation. How FIRS modulates the hippocampal immune response to acute postnatal inflammatory events is not well understood. METHODS: Prenatal LPS exposed (FIRS) and control neonatal rats received i.p. LPS or saline at postnatal day (P) 5. On P7, immune response was evaluated in the hippocampus of four treatment groups by measuring gene expression of inflammatory mediators and cytosolic and nuclear NFκB pathway proteins. Microglial activation was determined by CD11b+ and Iba1+ immunohistochemistry (IHC) and inflammatory gene expression of isolated microglia. Astrocyte reactivity was measured using Gfap+ IHC. RESULTS: Postnatal LPS resulted in a robust hippocampal inflammatory response. In contrast, FIRS induced by prenatal LPS attenuated the response to postnatal LPS exposure, evidenced by decreased gene expression of inflammatory mediators, decreased nuclear NFκB p65 protein, and fewer activated CD11b+ and Iba1+ microglia. Isolated microglia demonstrated inflammatory gene upregulation to postnatal LPS without evidence of immune tolerance by prenatal LPS. CONCLUSION: Prenatal LPS exposure induced immune tolerance to subsequent postnatal LPS exposure in the hippocampus. Microglia demonstrate a robust inflammatory response to postnatal LPS, but only a partial immune tolerance response.

Treatment of Hypothermic Cardiac Arrest in the Pediatric Drowning Victim, a Case Report, and Systematic Review.

OBJECTIVES: Drowning is the second leading cause of death in children. Extracorporeal membrane oxygenation (ECMO) has become the criterion standard therapy to resuscitate the hypothermic drowning victim in cardiac arrest. We present our own experience treating 5 children with hypothermic cardiac arrest in conjunction with a systematic review to analyze clinical features predictive of survival. METHODS: Our search resulted in 55 articles. Inclusion criteria were as follows: (1) younger than 18 years, (2) ECMO therapy, and (3) drowning. Ten articles met our inclusion criteria. We included studies using both central and peripheral ECMO and salt or fresh water submersions. We compared clinical features of survivors to nonsurvivors. RESULTS: A total of 29 patients from the 10 different studies met our criteria. Data analyzed included presenting cardiac rhythm, time to initiation of ECMO, submersion time, pH, potassium, lactate, duration of chest compressions, and survival. There was a significant increase in mortality for presenting rhythm of asystole and with hyperkalemia (P < 0.05). CONCLUSIONS: Extracorporeal membrane oxygenation is an important resuscitation tool for the hypothermic drowning victim. Hyperkalemia and presenting cardiac rhythm correlate with survival although they are not reasons to end resuscitation. More studies are needed to compare the outcomes in using ECMO for the hypothermic drowning victim.

Ocular Injury Presenting to a Level-III Pediatric Trauma Center.

The purpose of this study is to describe pediatric ocular injuries presenting to a level-III pediatric trauma center and emergency department. METHODS: We performed a retrospective study and identified children from January 1, 2011, to January 1, 2016. Charts were reviewed for any subject, age from newborn to younger than 18 years, based on International Classification of Diseases, ninth and tenth revision, codes for any ocular injury. Data abstraction included age, sex, means of arrival, eye involved, mechanism of injury, type of ocular injury, imaging studies obtained, procedures performed, location of definitive repair (in the operating room or emergency department), and subspecialty services involved. RESULTS: In the 5-year period, we describe 356 injuries among 278 children. Males had a slightly higher rate of presentation than females (156 and 122, respectively). Forty-three children (15.46%) required repair in the operating room. Dog bites comprised of 7.19% children with outpatient follow-up, one patient (0.36%) eventually developed anophthalmia, and 30 children (10.79%) had long-term ophthalmological sequelae (ie, glaucoma and blindness). CONCLUSIONS: At our institution, a level-III trauma center, we evaluated and managed approximately 1 ocular injury case per week and children required surgical repair in the operating room at a higher rate than higher-level trauma centers. Injuries secondary to dog bites remain a clinically significant etiology.

Prescription Opioids induce Gut Dysbiosis and Exacerbate Colitis in a Murine Model of Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Opioids are the most prescribed analgesics for pain in inflammatory bowel diseases [IBD]; however, the consequences of opioid use on IBD severity are not well defined. This is the first study investigating consequences of hydromorphone in both dextran sodium sulphate [DSS]-induced colitis and spontaneous colitis (IL-10 knockout [IL-10-/-]) mouse models of IBD. METHODS: To determine the consequences of opioids on IBD pathogenesis, wild-type [WT] mice were treated with clinically relevant doses of hydromorphone and colitis was induced via 3% DSS in drinking water for 5 days. In parallel we also determined the consequences of opioids in a spontaneous colitis model. RESULTS: Hydromorphone and DSS independently induced barrier dysfunction, bacterial translocation, disruption of tight junction organisation and increased intestinal and systemic inflammation, which were exacerbated in mice receiving hydromorphone in combination with DSS. Hydromorphone + DSS-treated mice exhibited significant microbial dysbiosis. Predictive metagenomic analysis of the gut microbiota revealed high abundance in the bacterial communities associated with virulence, antibiotic resistance, toxin production, and inflammatory properties. Hydromorphone modulates tight junction organisation in a myosin light chain kinase [MLCK]-dependent manner. Treatment with MLCK inhibitor ML-7 ameliorates the detrimental effects of hydromorphone on DSS-induced colitis and thus decreases severity of IBD. Similarly, we demonstrated that hydromorphone treatment in IL-10-/- mice resulted in accelerated clinical manifestations of colitis compared with control mice. CONCLUSIONS: Opioids used for pain management in IBD accelerate IBD progression by dysregulation of the gut microbiota, leading to expansion of pathogenic bacteria, translocation of bacteria, immune deregulation and sustained inflammation.

Pediatric Trauma Experience After Transition to a Freestanding Children's Hospital.

INTRODUCTION: Transition of pediatrics services to freestanding children's hospitals is a common trend over the past 3 decades, yet there is no published information on the effect of these moves on the pediatric emergency department (ED). We looked at the effect on trauma volume and severity presenting to the ED after transitioning to a freestanding children's hospital at a location previously without dedicated pediatrics services. METHODS: We analyzed data using a retrospective chart review of pediatric trauma visits (age, <15 years) from our pediatric trauma registry. Data analyzed included trauma volume per year, injury severity score, method of trauma, and method of arrival to hospital. Patients were differentiated into groups based on premove years (2008-2010) and postmove years (2012-2014). RESULTS: A total of 833 trauma patients were admitted to the ED between 2008 and 2014. Trauma volume per year almost doubled in years after the move. Difference in injury severity score and methods of trauma were not statistically significant. In postmove years, there was an increase in emergency medical service and private vehicle visits. CONCLUSIONS: New characteristics and location of the freestanding children's hospital may suggest that easy access to the new location, parental preferences for specialized pediatrics services, and emergency medical service preferences may have positively impacted trauma volume without affecting the severity of trauma seen in our department. This study provides a unique single-center experience in understanding ED patient flow after a major department transition.

A systematic review of management options in pediatric rectal prolapse.

PURPOSE: Rectal prolapse is a relatively common condition in infants and young children with a multifactorial etiology. Despite its prevalence, there remains clinical equipoise with respect to secondary treatment in pediatric surgery literature. We conducted a systematic review to evaluate methods of secondary treatment currently used to treat rectal prolapse in children. METHODS: We searched Pubmed, Medline, and Scopus with the terms "rectal prolapse" and "children" for papers published from 1990 to April 2017. Papers satisfying strict criteria were analyzed for patient demographics, intervention, efficacy, and complications. Procedures were grouped by like type. Pooled success rates were calculated. RESULTS: Twenty-seven studies documenting 907 patients were included. Injection sclerotherapy had an overall initial success rate of 79.5%. Ethyl alcohol seemed the best sclerosing agent due to a high first-injection success rate, low complication rate, and ready accessibility. Several perineal repairs were found, with operative success rates ranging from 60.8%-100%. Laparoscopic rectopexy with mesh was the most commonly reported transabdominal procedure and had an overall success rate of 96.1%. Postoperative complications from all procedures were comparable. CONCLUSION: Though many secondary treatment options have been reported for rectal prolapse, sclerotherapy and laparoscopic rectopexy predominate in contemporary literature and appear to have high success and low complication rates. LEVEL OF EVIDENCE: IV.

Emergency Management of the Ingested Magnet: An Algorithmic Approach.

INTRODUCTION: Accidental ingestion of foreign bodies is an increasing problem in the pediatric population. Symptoms are often nonspecific and may lead to a missed diagnosis because the ingestion event often goes unwitnessed. CASE: We present a case of a missed diagnosis of a multiple magnet ingestion event in a pediatric patient leading to operative management. A 2-year-old boy with a 4-week history of nonspecific abdominal pain presented to the emergency department (ED) with vomiting and worsening abdominal pain. He was recently seen in the ED for nonspecific abdominal pain diagnosed as acute otitis media. In this second ED visit, the child was found to be febrile and tachycardic and had signs of peritonitis. Radiographs revealed a foreign body in the right lower quadrant. The child was taken to the operating room where multiple intestinal perforations were identified and repaired. The child had an uneventful postoperative course and was discharged 7 days later. DISCUSSION: There are increasing awareness and growing concern over complications from pediatric magnet ingestion. Complications from neodymium magnet ingestion may include bowel obstruction, perforation, and fistula formation. The risk of complications is especially high with multiple-magnet ingestion. Pediatric foreign-body magnet ingestion may be a diagnostic challenge because the associated symptoms are nonspecific, and the ingestion is often unwitnessed. CONCLUSIONS: Our case represents the missed diagnosis of 4 magnets ingested separately over time. Emergency department providers may benefit from a clinical algorithm guiding the management of these increasingly prevalent patient presentations to prevent delayed diagnoses and to decrease morbidity.

Opioids Impair Intestinal Epithelial Repair in HIV-Infected Humanized Mice.

Intestinal barrier dysfunction and subsequent microbial translocation play crucial roles in persistent immune activation leading to HIV disease progression. Opioid use is associated with worse outcome in HIV-infected patients. The exacerbated disease progression by opioids is mainly driven by excessive intestinal inflammation and increased gut permeability. The objective of this study is to investigate how opioids potentiate HIV disease progression by compromising intestinal barrier function and impairing intestinal epithelial self-repair mechanism. In the present study, abnormal intestinal morphology and reduced epithelial proliferation were observed in bone marrow-liver-thymus humanized mice and in HIV-infected patients who were exposed to opioids. In bone marrow-liver-thymus mice, HIV, and morphine independently, and additively induced gut dysbiosis, especially depletion of Lachnospiraceae, Ruminococcaceae, and Muribaculaceae. We also observed that the abundance of Lachnospiraceae, Ruminococcaceae, and Muribaculaceae negatively correlated with apoptosis of epithelial cells, and intestinal IL-6 levels. Previous studies have shown that these bacterial families play crucial roles in maintaining intestinal homeostasis because they include most short-chain fatty acid-producing members. Short-chain fatty acids have been shown to maintain stem cell populations and suppress inflammation in the gut by inhibiting histone deacetylases (HDAC). In addition, we demonstrate that morphine exposure inhibited growth of intestinal organoids derived from HIV transgenic mice by suppressing Notch signaling in an HDAC-dependent manner. These studies implicate an important role for HDAC in intestinal homeostasis and supports HDAC modulation as a therapeutic intervention in improving care of HIV patients, especially in opioid-abusing population.

Standardized irrigation technique reduces intraabdominal abscess after appendectomy.

PURPOSE: The utility of irrigation at the time of appendectomy for acute appendicitis has been debated, with recent studies showing no benefit to irrigation. In our practice, two techniques have been used; one in which irrigation was at the discretion of the surgeon, and one in which irrigation was standardized. The standardized irrigation technique involved large volume (3-12 l) irrigation in small, focused, directed aliquots to achieve optimal dilution. We sought to retrospectively assess whether the standardized large volume irrigation technique was associated with measurably reduced intraabdominal infection. We hypothesized that there would be no difference in intraabdominal infection rate. METHODS: Medical records for cases of appendectomies performed for acute appendicitis, years 2007 through 2017, were reviewed (n = 432). Rate of subsequent abdominal infection was compared between patients who underwent the standardized large volume irrigation technique compared to those who did not using Fisher's exact test; p < 0.05 was considered significant. RESULTS: For patients that underwent the standardized large volume irrigation technique there were no (0/140) subsequent abdominal infections within the study period, compared with a rate of 6.2% (18/292) for all other patients (p value 0.001). Among cases that had a perforated appendix (n = 105), the rates were 0% (0/31) compared to 18.9% (14/74; p value 0.009). CONCLUSIONS: Utilization of a standardized large volume irrigation technique with the objective of serial dilution is associated with a significantly lower rate of subsequent abdominal infection, even among cases with a perforated appendix. Prospective studies are needed to evaluate this technique. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Treatment study.

Combined laparoscopic-fluoroscopic technique for primary gastrojejunostomy button tube placement.

BACKGROUND: Gastrojejunostomy (GJ) tubes are frequently used to provide pediatric enteral nutritional support for pediatric patients. Various placement methods have been described, each with attendant advantages and disadvantages. DESCRIPTION OF THE OPERATIVE TECHNIQUE: We present a technique for primary laparoscopic/fluoroscopic GJ button tube placement designed to avoid delay in placement of the jejunal limb, and difficulties associated with endoscopic-assisted and primary fluoroscopic placement. RESULTS: There were 52 gastrojejunostomy button tubes placed via this technique in patients ranging from 3.8 to 90.3 kg in weight. Three postoperative complications were identified; one bowel perforation on postoperative day two, and two tube dislodgements within 30 days. CONCLUSION: The described technique was uniformly effective and was associated with a low complication rate (5.8%).

Peritoneal dialysis catheter placement, outcomes and complications.

PURPOSE: Peritoneal dialysis (PD) is a commonly used method for renal support in pediatric patients and can be associated with the risk of post-surgical complications. We evaluated method of placement of PD catheters with regard to post-surgical complications. METHODS: PD catheters placed at two institutions between 2005 and 2017 were reviewed. Complication rates were evaluated based on method of placement, delayed usage, omentectomy, and patient age using Fisher's exact test, two-sided, with significance set at 0.05. Factors influencing complication were evaluated with multivariate logistic regression and Kaplan-Meier survival analysis. RESULTS: There were 130 patients with 157 catheters placed, ranging in age from 1 day to 23 years. There was no significant difference in complication rate by method of placement or delayed usage. Infants were significantly more likely to experience leakage (21% vs 8%, p 0.036) and hernias (15% vs 5%, p 0.030). Patients that underwent an omentectomy were less likely to require a catheter replacement (7% vs 27%, p 0.004), and the catheters had a significantly higher survival rate (p 0.009). We found that laparoscopic intervention resulted in catheter salvage. Lateral exit sites may be a risk factor for catheter migration in some patients. CONCLUSIONS: Omentectomy is associated with longer PD catheter survival. Laparoscopic salvage of dysfunctional catheters may be a valuable adjunct in management.

Radial umbilical dermatofasciolysis to invert the skin following umbilical herniorrhaphy.

BACKGROUND: Umbilical hernia is a common congenital anomaly, and can result in the appearance of a protuberant umbilicus. In select cases, inversion of the umbilical skin can be impaired by the presence of thickened dermis or fascial remnants of the umbilical stalk. DESCRIPTION OF OPERATIVE TECHNIQUE: After umbilical herniorrhaphy, the skin is everted over the left index finger and radial partial thickness incisions in the fascia and dermis of the undersurface of the umbilicus. The umbilical skin is then inverted and secured to the fascia. CONCLUSION: This operative technique can allow complete inversion of the umbilical skin creating an aesthetically appealing umbilical hernia repair.

Prescription opioids are associated with higher mortality in patients diagnosed with sepsis: A retrospective cohort study using electronic health records.

Sepsis continues to be a major problem for hospitalized patients. Opioids are widely used medications for pain management despite recent evidence revealing their adverse effects. The present study evaluates survival differences between opioid-treated patients and non-opioid-treated patients hospitalized with a diagnosis of sepsis. Clinical data was extracted from the University of Minnesota's Clinical Data Repository, which includes Electronic Health Records (EHRs) of the patients seen at 8 hospitals. Among 5,994 patients diagnosed with sepsis, 4,540 opioid-treated patients and 1,454 non-opioid patients were included based on whether they are exposed to prescription opioids during their hospitalization. Cox proportional hazards regression showed that after adjustments for demographics, clinical comorbidities, severity of illness, and types of infection, opioid-treated patients had a significantly higher risk of death at 28 days.

Enteric glial-mediated enhancement of intestinal barrier integrity is compromised by morphine.

BACKGROUND: The opioid epidemic is a growing concern, and emerging evidence suggests that morphine use may be associated with sepsis. Enteric glial cells (EGCs) are the most numerous cell type in the enteric nervous system and regulate gastrointestinal function through the production of trophic factors, including glial-derived neurotrophic factor (GDNF). We sought to determine the effect of morphine on enteric glia and hypothesized that morphine contributes to EGC dysfunction and increased gut permeability. MATERIALS AND METHODS: Rat intestinal epithelial cells (IECs) and EGC lines were purchased from ATCC. Immunocytochemistry was used to evaluate the impact of EGCs on IEC barrier proteins and detect the µ-opioid receptor. Co-culture assays were used to determine the effect of EGCs, GDNF, and morphine on barrier integrity. Quantitative polymerase chain reaction and western blotting were performed to determine the impact of morphine in GDNF production. Transepithelial resistance of IEC-6 cell monolayers was measured in the presence of EGC-conditioned media (EGC-CM) and morphine treated EGC-CM using electrical cell impedance sensing. RESULTS: EGC-CM enhanced tight junction organization in IECs. IEC barrier integrity was enhanced when co-cultured with unstimulated EGCs or with GDNF alone; this barrier protective effect was lost with morphine-treated EGCs. GDNF RNA and protein expression were decreased by morphine treatment. Transepithelial resistance was decreased in IEC confluent monolayers when exposed to morphine-treated EGC-CM compared with control. CONCLUSIONS: Morphine compromises intestinal epithelial cell barrier function through a mechanism which appears to involve GDNF. Further studies are warranted to delineate the role of enteric glial cell function in opioid signaling and sepsis.

An occult ectopic parathyroid adenoma in a pediatric patient: a case report and management algorithm.

BACKGROUND: Hyperparathyroidism (HPT) is a rare disease in the pediatric population, and optimal management may be unclear if it is due to an occult parathyroid adenoma. We present a case report of a pediatric patient with an occult, ectopic, supernumerary, parathyroid adenoma. CASE PRESENTATION: A 13-year-old female who initially presented with anxiety was diagnosed with HPT. Preoperative imaging and bilateral neck exploration with four-gland biopsy were negative for any parathyroid adenoma. Postoperative MRI identified a thymic mass. She subsequently underwent video-assisted thoracoscopic thymectomy with resection of an intrathymic parathyroid adenoma. CONCLUSIONS: The diagnosis of pediatric HPT is increasing. Supernumerary or occult parathyroid adenomas are rare and add complexity to presurgical planning and management. Our case represents the rare occurrence of a pediatric ectopic supernumerary occult parathyroid adenoma treated with a two-stage approach utilizing multiple imaging studies. We provide a review of the pathology and propose an algorithmic approach to manage these complex patients.