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.

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.

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.

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.

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.

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.

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.

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.

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.