Defective monocyte plasticity and altered cAMP pathway characterize USB1-mutated poikiloderma with neutropenia Clericuzio type.

Poikiloderma with neutropenia (PN) Clericuzio type (OMIM #604173) is a rare disease with areas of skin hyper- and hypopigmentation caused by biallelic USB1 variants. The current study was spurred by poor healing of a perianal tear wound in one affected child homozygous for c.266-1G>A (p.E90Sfster8) mutation, from a family reported previously. Treatment with G-CSF/CSF3 or GM-CSF/CSF2 transiently increased neutrophil/monocytes count with no effect on wound healing. Analysis of peripheral blood revealed a lack of non-classical (CD14+/- CD16+ ) monocytes, associated with a systemic inflammatory cytokine profile, in the two affected brothers. Importantly, despite normal expression of cognate receptors, monocytes from PN patients did not respond to M-CSF or IL-34 in vitro, as determined by cytokine secretion or CD16 expression. RNAseq of monocytes showed 293 differentially expressed genes, including significant downregulation of GATA2, AKAP6 and PDE4DIP that are associated with leucocyte differentiation and cyclic adenosine monophosphate (cAMP) signalling. Notably, the plasma cAMP was significantly low in the PN patients. Our study revealed a novel association of PN with a lack of non-classical monocyte population. The defects in monocyte plasticity may contribute to disease manifestations in PN and a defective cAMP signalling may be the primary effect of the splicing errors caused by USB1 mutation.

Utilization of Imaging in the Management of Pediatric Dog Bites.

INTRODUCTION: We hypothesized that imaging is overused in the initial workup of dog bite patients. To reduce radiation exposure, we aim to determine which circumstances surrounding dog bites, patient population, and injury patterns would necessitate imaging studies for management. METHODS: A retrospective review was performed on all patients presenting with dog bites to our level I pediatric trauma center between 2013 and 2015. Data collected included: circumstances surrounding the injury, patient demographics, injuries, and imaging studies performed. Our analysis focused on maxillofacial and head CT scans, and plain radiographic studies of the limbs, hands, and feet. Imaging studies were considered positive if there was evidence of bony injury. RESULTS: We identified 615 patients with dog bites, with 114 patients having had at least one imaging study performed (a total of 145 imaging studies to analyze). Only 13 (11%) patients had a positive study. In the CT scan group, 6 (22.2%) of 27 studies were positive. In the plain radiographic group, 7 (5.9%) of 118 studies were positive. CONCLUSIONS: Our review indicates that imaging studies are overused in the initial workup of these patients, and the majority of these studies are negative. This study confirms that it is feasible to institute guidelines for ordering imaging studies in dog bite patients. This will ultimately reduce radiation exposure and the cost of care for these injuries.

Initial Laparotomy Versus Peritoneal Drainage in Extremely Low Birthweight Infants With Surgical Necrotizing Enterocolitis or Isolated Intestinal Perforation: A Multicenter Randomized Clinical Trial.

OBJECTIVE: The aim of this study was to determine which initial surgical treatment results in the lowest rate of death or neurodevelopmental impairment (NDI) in premature infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP). SUMMARY BACKGROUND DATA: The impact of initial laparotomy versus peritoneal drainage for NEC or IP on the rate of death or NDI in extremely low birth weight infants is unknown. METHODS: We conducted the largest feasible randomized trial in 20 US centers, comparing initial laparotomy versus peritoneal drainage. The primary outcome was a composite of death or NDI at 18 to 22 months corrected age, analyzed using prespecified frequentist and Bayesian approaches. RESULTS: Of 992 eligible infants, 310 were randomized and 96% had primary outcome assessed. Death or NDI occurred in 69% of infants in the laparotomy group versus 70% with drainage [adjusted relative risk (aRR) 1.0; 95% confidence interval (CI): 0.87-1.14]. A preplanned analysis identified an interaction between preoperative diagnosis and treatment group (P = 0.03). With a preoperative diagnosis of NEC, death or NDI occurred in 69% after laparotomy versus 85% with drainage (aRR 0.81; 95% CI: 0.64-1.04). The Bayesian posterior probability that laparotomy was beneficial (risk difference <0) for a preoperative diagnosis of NEC was 97%. For preoperative diagnosis of IP, death or NDI occurred in 69% after laparotomy versus 63% with drainage (aRR, 1.11; 95% CI: 0.95-1.31); Bayesian probability of benefit with laparotomy = 18%. CONCLUSIONS: There was no overall difference in death or NDI rates at 18 to 22 months corrected age between initial laparotomy versus drainage. However, the preoperative diagnosis of NEC or IP modified the impact of initial treatment.

Initial blood cultures in pediatric patients with central line infections and short bowel syndrome can direct a treatment plan that can reduce hospital length of stay.

BACKGROUND: Children with short bowel syndrome requiring parenteral nutrition are at high risk of recurrent central line-associated bloodstream infections requiring inpatient admission. Predicting responses to treatment at admission could help revise our current treatment algorithm and reduce the length of stay. METHODS: We conducted a retrospective study of all intestinal rehabilitation clinic patients admitted for central line-associated bloodstream infections at our academic hospital between January 2018 and June 2021. Demographic, blood culture, and treatment response data were analyzed. RESULTS: There were 180 separate admissions for central line-associated bloodstream infections, involving 24 patients who met the inclusion and exclusion criteria. The average length of stay was 9.4 days, and 77.1% of the admissions exceeded the predicted length of stay. All patients were treated according to the standard protocols. In the initial blood cultures, 64.4%, 10.6%, and 25% grew a single bacterium, a single fungus, and multiple organisms, respectively. After treatment initiation, 73.3% of single bacterial infections did not show additional positive cultures. However, 78.9% and 48.9% of fungal and multiple organism infections, respectively, had multiple positive cultures, even after initiating treatment. All positive repeat cultures were treated with an ethanol lock for 24 hours in addition to continued treatment. The treatment preserved 90.5% of the catheters. CONCLUSION: Patients experiencing short bowel syndrome admitted for central line-associated bloodstream infections with initial cultures growing fungi or multiple organisms frequently had multiple positive cultures, whereas those with a single bacterial organism did not. Discharging patients who grew a single bacterial organism and placing an initial ethanol lock on those with multiple or fungal organisms could reduce the average length of stay, even if some of these patients would require readmission for line removal.

Weight-based vs body surface area-based fluid resuscitation predictions in pediatric burn patients.

Treatment for pediatric burns includes fluid resuscitation with formulas estimating fluid requirements based on weight and/or body surface area (BSA) with percent total body surface area burn (%TBSA burn). This study evaluates the risk of complications using weight-based resuscitation in children following burn injuries and compares fluid estimates with those that incorporate BSA. A retrospective review was conducted on 110 children admitted to an ABA-verified urban pediatric burn center over 12 years. Patients had ≥ 15% TBSA burn and were resuscitated with the weight-based Parkland formula. BSA-based Galveston and BSA-incorporated Cincinnati formula predictions were calculated. Complications were collected throughout hospital stay. Patients were classified into weight groups based on percentile. This study included 11 underweight, 60 normal weight, 18 overweight, and 21 obese children. Total fluid administered was higher as percentile increased; however, overweight children received more fluid than the obese (p = 0.023). The Galveston formula underpredicted fluid given over the first 24 h post-injury (p = 0.042); the Parkland and Cincinnati formula predictions did not significantly differ from fluids given. Further research is needed to determine the value of weight-based vs BSA-based or incorporated formulas in reducing risk of complications.

Factors associated with an extended length of stay in the pediatric burn patient.

BACKGROUND: The Center for Medicaid and Medicare Services predicts the length of stay for pediatric burn patients based on several variables. However, many patients exceed their anticipated length. This study looks to identify aspects of patient presentation, wound characteristics, treatment, and discharge that are associated with a longer-than-predicted length of stay to identify strategies to safely reduce it. METHODS: We conducted a retrospective chart review of 535 pediatric burn patients admitted to our academic hospital from January 2018 to December 2020. 405 patients met inclusion criteria. Data were collected and analyzed. RESULTS: Average patient age was 3.36 years. 72.3% were treated for scald burns. Average length of stay was 13.5 days. 20.5% (n = 83) of patients exceeded their predicted length of stay. In comparing patients who exceeded their predicted length of stay to those who did not, the former had significant differences in burn causes, percent total body surface area burned (12.80% vs 4.24% [P = .000]), and body areas involved. Patients who exceeded length of stay had a higher incidence of endotracheal intubation (15.7% vs 1.3%), surgical intervention (85.5% vs 29.2%), need for tube-feeding (48.2% vs 4.3%), and intensive care unit admissions (22.9% vs 2.2% [P = .00 all]). They also averaged more operations, autografting (31.3% vs 1.6% [P = .00]), total operating room time (250 vs 31 minutes [P = .00]), and time to the first operation (2.32 vs 1.64 days [P = .00]). Tube-feeding averaged 9.52 vs 0.72 days (P = .00) extending patient stay after wound stability (43.9% vs 4.3% [P = .00]). These patients also required more discharge planning, with higher rates of Child Protective Services involvement (39.8% vs 10.9% [P = .00]), services consulted (1.06 vs 0.24 [P = .00]), and discharges to inpatient rehabilitation (8.6% vs 0.6% [P = .00]). 89.6% of all patients followed up in clinic. CONCLUSIONS: Twenty percent of pediatric burn patients had a longer length of stay than predicted by the Center for Medicaid and Medicare Services. Many factors were strongly associated with a longer-than-predicted length of stay. Identifying these early on might help reduce length of stay and meet the targets of the Center for Medicaid and Medicare Services.

A Retrospective Study of Touchless Spray for Pediatric Perineal Burns Treatment.

Silver-based topical treatments have seen widespread use for the management of burns due to silver's antimicrobial activity. Recent studies suggest that silver nanoparticles could negatively affect healing time due to their toxic effect on keratinocytes and fibroblasts at higher concentrations. Zinc oxide antimicrobial activity has been demonstrated in vitro, and results from animal studies are promising for burn management. At our ABA-verified pediatric burn center, the use of silver sulfadiazine cream ("Silvadene") has been slowly replaced by a zinc oxide/dimethicone spray-on solution ("Touchless Spray"). The dimethicone allows the spray to be occlusive without interfering with clothing, yet easily removed as opposed to Silvadene cream which requires wound scrubbing to remove and replace; potentially improving patient adherence with at-home treatments. This is the first study of zinc oxide's efficacy as a burn wound management agent in humans. We sought to compare the efficacy of silver sulfadiazine and that of zinc oxide/dimethicone to determine whether zinc oxide/dimethicone, in its easy-to-use form, is a viable alternative to silver sulfadiazine. We conducted a retrospective review of the electronic medical records of all patients treated for perineal, genital, perianal, suprapubic, or buttocks burn wounds at a large pediatric-verified burn center from January 1, 2014 to October 28, 2019. Only patients with superficial second-degree scald burns that arrived at our institution less than 24 hours after injury were included. Of a total 52 patients identified, 27 patients received silver sulfadiazine while 25 received zinc oxide/dimethicone. After initial evaluation and treatment by the burn team, all patients were followed up at our weekly burn clinic until complete healing was achieved. We retrospectively extracted demographic data, wound size, depth, and location, management strategies, time to complete healing, and incidence of infectious and noninfectious complications. The control group contained patients with total body surface area burns significantly greater than the zinc oxide/dimethicone group likely due to selective treatment when zinc oxide/dimethicone was first introduced at our facility. Time to healing was significantly lower in the zinc oxide/dimethicone intervention group (12.16 ± 8.644 days) than the silver sulfadiazine control group (16.89 ± 11.342 days). No infections were observed. Limitations include the relatively small sample sizes and differences in the size of burn wounds that confounded our results and likely negatively affected healing time in the control group. The zinc oxide/dimethicone group had a significantly lower healing time than the silver sulfadiazine group in the treatment of pediatric burns to the perineum, genitalia, suprapubis, and buttocks. Zinc oxide/dimethicone may prove to be a useful tool for treating burn wounds, and further study is needed to determine its efficacy and safety.

Outcomes of Early Surgical vs Nonsurgical Management of Pediatric Hand Friction Injuries Caused by Treadmills.

Pediatric hand friction injuries caused by running treadmills are ever more prevalent due to the increasing presence of home exercise equipment. These and other related injuries have received recent attention in the media, leading to mass product recalls in some cases. These friction injuries are similar to deep thermal burns, and these patients are usually cared for in the pediatric burn unit at our institution. We sought to describe our recent experience managing 22 patients with these injuries. Patients were queried from our urban pediatric burn center database. After Institutional Review Board approval, a retrospective chart review of all patients admitted for a treadmill-related hand injury over a 5-year period was performed. Data collected included patient demographics, initial treatment methods (surgical vs nonoperative), type of dressing used, hospital length of stay (LOS), and compliance with follow-up. We collected patient-centered outcomes included the time to healing and the need for subsequent surgical and/or nonsurgical interventions to treat the sequelae of these injuries. Our center treated 22 hand friction injuries caused by treadmills over the 5-year period. Five patients (23%) underwent early surgical intervention (<30 days from injury), with a median time from injury of 7 days (interquartile range 1.75-13.5). This cohort required additional interventions to treat postoperative sequelae with 2 (40%) requiring additional surgery and 3 (60%) managed nonsurgically. Of the 17 (77%) who were initially treated nonoperatively, 5 (29%) healed completely with dressing changes only and required no further treatment. Eleven (65%) had injury-related sequelae and were managed successfully with nonsurgical interventions. Only 1 patient (6%) required scar modification by Z-plasty. Average LOS was 14 hours and the median number of weekly follow-up visits was 4 until complete healing. Given the excellent outcomes observed in patients treated without acute surgical intervention in this case series, nonoperative management appears to be feasible, safe, and may reduce the need for operative intervention. These injuries, although small, are deep and require a prolonged period of dressing changes and aggressive therapy including posthealing time commitment to scar management in order to achieve best outcomes. Our study supports the need for increased community awareness of this type of injury.

Sink bathing burns: A unique opportunity for an injury prevention initiative.

Sink-bathing is common practice among parents. However, this puts infants and young children at unrecognized risk for burn injuries. As the only verified pediatric burn center in a large urban area, we treat burn patients from a large variation in socioeconomic status. This provides us a unique opportunity to examine sink-burn injury patterns, circumstances surrounding these burns, identify areas with high incidence and put in place an injury prevention outreach initiative. This retrospective study included patients treated for sink-bathing burns at our burn center in an 8.5-year period. Analysis of 71 patients revealed infants under one year of age are most commonly afflicted. Additionally, that families of low-socioeconomic means are disproportionately affected. Understanding the different circumstances surrounding sink-bathing burns allows us to be more specific in our community education efforts and efficiently guide our resources.

Circumstances surrounding gun violence with youths in an urban setting.

BACKGROUND: Our pediatric trauma center has noted an increase in the occurrence of gunshot wounds in children. We aimed to understand the circumstances surrounding these injuries in order to provide targeted injury prevention methodologies. METHODS: A retrospective review was performed on patients who presented with a gunshot wound to our Level I Pediatric Trauma Center and two neighboring Adult Trauma Centers between 2013 and 2017. RESULTS: Three hundred twenty-six patients (6 months to 18 years) were treated for gunshot wounds. Patients were African American (86%), Caucasian (9%), and other races (5%). Eight zip-codes were identified as high-risk, accounting for 52% of patients. Most injuries (86%) were from powder firearms. Known circumstances (n = 275) included drive-by shootings (47%), unlocked guns (19%), crime related (13%), altercation between adolescents (7%), cross-fire from adult altercation (6%), home invasion (6%), and suicide attempts (2%). There was a progressive increase of 50% over the last 4 years. The increase in incidence was predominantly from an increase in drive-by shootings; however, the incidence of injuries from unlocked guns has remained relatively constant per year. Mortality was 6%. CONCLUSION: Identifying high-risk zones for drive-by shootings and other crimes is critical for developing system-focused interventions. Zip-code data stratified by age and circumstances, will allow for targeted community outreach on gun safety education, in an effort to reduce the incidence of injuries from unlocked guns. LEVEL OF EVIDENCE: Prognostic and Epidemiologic study, Level III.

Cystic lung disease.

Cystic lung disease is divided into congenital and acquired lesions. Congenital cystic lung disease includes several malformations with distinct anatomical and histological features. There is significant overlap between these lesions to suggest a common pathologic mechanism for their occurrence. Congenital cystic lung lesions include cystic adenomatoid malformations, pulmonary sequestrations, congenital lobar emphysema, and peripheral bronchogenic cysts. These lesions are commonly diagnosed prenatally with high accuracy. Prenatal imaging has allowed us to better understand their natural history and devise strategies for prenatal and postnatal management. Some lesions warrant resection (even prenatally), whereas others can be managed expectantly.

Analysis of Electrocardiograms Associated with Pediatric Electrical Burns.

The purpose of this study was to examine the utility of electrocardiograms (EKGs) for low-risk, low-voltage pediatric electrical burn victims. A retrospective chart review was conducted on 86 pediatric patients who presented to the children's hospital between 2000 and 2015 after sustaining electrical burns. Variables included source and estimated voltage, extent of injuries, length of stay, high risk factors, and EKG results. High risk factors included estimated voltage > 1000 V, lightning, tetany, symptoms, loss of consciousness, or seizures. Statistical analyses were conducted. Average age was 5 years. Of those who sustained burns, 84.5% (n = 71/84) had second-degree burns ≤ 1% TBSA or less. Eleven patients had high risk factors, 12.9% (n = 11/85) and most had length of stay < 3 days (91.8%; n = 78/85). Majority sustained burns from low-voltage (< 300 V) household electrical outlets, cords, or light bulb sockets (90.4%; n = 75/83). Among patients with available EKGs, 12 had arrhythmias on initial EKG (i.e., low right atrial rhythm, t-wave inversions, sinus tachycardia, bundle branch block; 20.7%; n = 12/58). All were transient and nonfatal. The data suggest that low estimated voltage (< 300 V) electrical injuries were associated with negative EKGs; however, due to the low rate of arrhythmias, a Fisher's exact test did not show significance, P = 0.09 (P > 0.05). Preliminary data suggest that most pediatric electrical burns are due to low voltage (< 300 V) household sources. Few have high risk factors or arrhythmias that were transient and nonfatal. These data suggest that low-risk, asymptomatic, low-voltage pediatric electrical burns may not require an initial screening EKG.

Overview of current pediatric burn care.

Burn injuries affect approximately a million children in the United States on an annual basis. Moderate to severe burns require hospitalization, usually under the direction of a Pediatric Surgical service. Despite advancements in burn treatment, pediatric burn injuries account for approximately 2500 deaths annually. This article provides an overview of the initial evaluation and resuscitative measures for pediatric burn patients, most current wound care, indications for grafting, and the role of nutrition, including use of pharmacologic adjuncts. Use of colloid solutions, indications for use of skin substitutes, and transfer criteria will also be addressed.

Correlation of revised trauma score and injury severity score (TRISS) predicted probability of survival with peer-reviewed determination of trauma deaths.

Trauma deaths at our institution are evaluated by a multidisciplinary trauma committee. The purpose of this study was to evaluate preventable trauma deaths (PRDs) as determined by our review committee and correlate them with the Revised Trauma Score and Injury Severity Score (TRISS) probability of survival (PS). A total of 10,002 patients were identified. The PS was calculated using the TRISS method. The Z scores were calculated and the predicted number of deaths was established. The actual number of deaths was compared with the predicted number of deaths. PRDs were compared with the actual and predicted deaths. The Z score was 0.79, which meant we observed more deaths than predicted by TRISS. We had 281 deaths compared with 271 deaths predicted by TRISS. Peer review characterized 45 deaths as preventable. Although we performed well when our outcomes were compared with TRISS predicted outcomes our PRD rate was higher. The higher the PS the more likely the death was found preventable by peer review. We conclude that for our patient population the peer review process is very sensitive and may be more discerning in identifying PRD than TRISS.

Resection of giant liver adenoma in a 17-year-old adolescent boy using venovenous bypass, total hepatic vascular isolation, and in situ cooling.

Giant liver adenomas are rare pediatric tumors. Hepatocellular adenomas account for approximately 2% to 4% of all pediatric liver tumors. We present the case of a biopsy-proven 21 x 20.5 x 10.5-cm hepatocellular adenoma in a 17-year-old adolescent boy resected using venovenous bypass and total hepatic isolation. Hepatic adenomas of this size are historically treated with orthotopic liver transplantation. Resection of a massive centrally located giant liver adenoma using total hepatic vascular isolation and venovenous bypass with in situ hepatic cooling and is not previously reported. By combining these techniques, we were able to defer the risks of orthotopic liver transplantation and life-long immunosuppression for our patient. The patient's recovery was uncomplicated and hepatic regeneration was excellent. At 9 months' follow-up, the patient reported enjoying an athletic adolescent life-style with no evidence of recurrence.

Cocaine and the critical care challenge.

OBJECTIVE: Cocaine, which first made its appearance >1,000 yrs ago, is now widely used throughout the world. The physiologic responses to cocaine may cause severe pathologic effects. This review highlights the many critical care challenges resulting from these effects. DESIGN: Historical vignettes, epidemiologic factors, modes of preparation and delivery, and the physiologic and pharmacologic effects of these agents are presented. SETTING: Cocaine causes intense vasoconstriction, which potentially causes damage to all organ systems. Examples of these toxicities are presented. PATIENTS: The adverse multisystem responses to cocaine exposure produce organ failure, which challenges diagnostic accuracy and therapeutic intervention. Organ system failure involves the brain, heart, lung, kidneys, gastrointestinal tract, musculature, and other organs. These harmful effects are additive to preexisting organ dysfunction. INTERVENTION: Recognition of associated cocaine injury alerts the physician that organ dysfunction is more likely to occur and to be more severe. Such anticipation helps plan for therapy in the critical care setting. RESULTS AND CONCLUSIONS: Cocaine use is an expanding health hazard, despite intense governmental efforts to contain its distribution and use. Recognition of the signs and symptoms of cocaine toxicity help anticipate the subsequent organ dysfunction and implement earlier organ system support.