Enhanced Recovery After Surgery 2.0: Optimizing Pain Management in Nuss Procedure: Cryoablation and Nerve Block Strategies for Reduced Opioid Use.

INTRODUCTION: Our study assesses the association between cryoablation, with and without nerve block supplementation, post-Nuss procedure pain, and opioid use in pectus excavatum (PE) patients. METHODS: We conducted a retrospective cohort study at a single center for PE patients who underwent the Nuss procedure from 2017 to 2022. Outcomes included postoperative opioid use (measured in oral morphine milligram equivalent per kilogram [OME/kg]), average pain score (scale 0-10), and length of stay (LOS). RESULTS: One hundred sixty-four patients (146 males and 18 females) were included, with 79 (48.2%) receiving neither cryoablation nor nerve block, 60 (36.6%) receiving intraoperative cryoablation alone, and 25 (15.2%) receiving both cryoablation and nerve block. The median age was 16 y. Nerve block recipients consumed fewer opioids during hospitalization than cryoablation alone and nonintervention groups (1.5 versus 2.3 versus 5.8 OME/kg, respectively, P < 0.0001). Average pain scores over the total LOS were lower in nerve block recipients (3.5 versus 3.8 versus 4.2, P = 0.03), particularly on postoperative day 0 (P = 0.002). Nerve block recipients had a shorter LOS than cryoablation alone and nonintervention groups (43.4 versus 54.7 versus 66.2 h, P < 0.0001). On multivariate analysis, cryoablation alone resulted in significantly less opioid use compared to no intervention (3.32 OME/kg reduction, 95% confidence interval -4.16 to -2.47, P < 0.0001). Addition of nerve block further reduced opioid use by 1.10 OME/kg (95% confidence interval -2.07 to -0.14, P = 0.04). CONCLUSIONS: Cryoablation with nerve block supplementation is associated with reduced pain, opioid use, and LOS post-Nuss for PE repair compared to cases without cryoablation or with cryoablation only. Cryoablation with regional nerve blocks should be considered for Nuss repair under the enhanced recovery after surgery pathway.

Measuring Pectus Excavatum Severity, External Caliper, or Cross-Sectional Imaging: Family Perceptions.

INTRODUCTION: Patients with pectus excavatum (PE) often undergo cross-sectional imaging (CSI) to quantify severity for insurance authorization before surgical repair. The modified percent depth (MPD), an external caliper-based metric, was previously validated to be similar to the pectus index and correction index. This study explored family perceptions of CSI and MPD with respect to value and costs. METHODS: This is a cross-sectional survey study including families of patients enrolled in an ongoing prospective multicenter study evaluating the use of MPD as an alternative to CSI for quantifying PE severity. Families of PE patients who underwent both MPD and CSI completed a survey to determine their perceptions of MPD and costs of CSI. Responses were described and associations were evaluated using chi squared, Wilcoxon rank-sum test and logistic regression as appropriate. Statistical significance was set to 0.05. RESULTS: There were 136 surveys completed for a response rate of 88%. Respondents were confident in MPD (86%) and confident in its similarity to CSI (76%). Families of females were less confident in the measurements than males (55% versus 80%, P = 0.02; odds ratio 0.30 (0.11, 0.83). Obtaining CSI required time off work/school in 90% and a copay in 60%. Nearly half (49%) of respondents reported CSI was a time/financial hardship. Increasing copay led to decreased reassurance in CSI (55%: copay > $100 versus 77%: lower copay/75%: no copay; P = 0.04). CONCLUSIONS: From the family perspective, MPD is valuable in assessing the severity of PE. Obtaining CSI was financially burdensome, particularly for those with higher copays. MPD measurements provide high value at low cost in assessing the severity of PE.

Appendectomy and Cholecystectomy Outcomes for Pediatric Cancer Patients with Leukopenia: A NSQIP-Pediatric Study.

BACKGROUND: Children with cancer often develop leukopenia which may impair wound healing and increase surgical complication rates. When leukopenic children with cancer develop an acute surgical condition, the optimal management strategy remains unclear. This study examined the effect of preoperative leukopenia on postoperative outcomes in children with cancer who underwent an appendectomy or cholecystectomy. METHODS: We retrospectively identified cancer patients undergoing an appendectomy or cholecystectomy from the National Surgical Quality Improvement Program-Pediatric database from 2012-2018. Demographics and perioperative characteristics were compared by leukopenia status (WBC <4 vs. ≥4 × 10^3/mL). Postoperative length of stay (LOS) and 30-day composite complications, including infections, reoperations, and readmissions, were analyzed for each procedure using multivariate regression. RESULTS: There were 227 children who underwent an appendectomy and 101 children who underwent a cholecystectomy. Leukopenia was seen in 93 (41.0%) appendectomy and 57 (56.4%) cholecystectomy cases. Nineteen (8.4%) appendectomy patients and six (5.9%) cholecystectomy patients developed a postoperative complication. The median postoperative LOS was 2 days (IQR 1-6 days) for appendectomy and 1 day (IQR 1-2.5 days) for cholecystectomy cases. After multivariate analyses, leukopenia was not associated with increased postoperative complications after an appendectomy (OR 0.55, P = 0.36) or cholecystectomy (OR 0.39, P = 0.37). There was no significant difference in postoperative LOS based on leukopenia status for children who underwent an appendectomy (P = 0.82) or cholecystectomy (P = 0.37). CONCLUSION: In pediatric cancer patients, leukopenia was not associated with increased short-term postoperative complications or longer postoperative LOS after either an appendectomy or cholecystectomy. These results support that operative management can be performed safely in pediatric appendicitis and cholecystitis in leukopenic cancer patients.

Pediatric traumatic abdominal wall hernia as a component of the seatbelt syndrome: a case series and review of the literature.

BACKGROUND: Blunt impact-induced traumatic abdominal wall hernia (TAWH) is an uncommon pediatric surgical problem classically associated with handlebar injury but increasingly seen with seatbelt use in motor vehicle collisions (MVC). Herein we describe the largest case series of pediatric TAWH to date and review the literature to establish the unique syndromic characteristics of MVC-associated TAWH. METHODS: In this single-institution series, we discuss four pediatric patients, all with seatbelt-associated TAWH after high-speed MVC characterized by full-thickness disruption of the lateral abdominal wall. We then performed a review of the literature to identify additional pediatric MVC-associated TAWH and define the characteristics of patients who sustained this unique injury. RESULTS: In addition to the four patients in our case series, five additional pediatric patients presenting with TAWH after restrained MVC were identified in the literature. Of these nine patients, eight (89%) presented with an obvious seatbelt sign (bruising/laceration to the abdominal wall). Six (67%) had associated injuries typical of the seatbelt syndrome, including four spinal flexion injuries (44%) and five bowel injuries requiring repair or resection (56%). Overall, 56% of seatbelt-associated TAWH occurred in children with a BMI percentile > 95%. CONCLUSIONS: In this case series and literature review, we note a high rate of seatbelt syndrome injuries in pediatric patients presenting with TAWH after restrained MVC. Suspicion for TAWH should be high in children presenting with a seatbelt sign and should trigger a low threshold for pursuing additional axial imaging. LEVEL OF EVIDENCE: Level IV; case series.

Artiss fibrin sealant for the fixation of autografts in pediatric burn care.

BACKGROUND: Traditional fixation of autografts in the treatment of burns involves the use of sutures and staples. A novel fibrin sealant, Artiss, has been introduced as an alternate method of fixation and has shown promising safety and efficacy results in the adult population. Our study assessed the effectiveness of fibrin sealant to secure autologous split thickness skin grafts (ASTSG) in the pediatric burn population. METHODS: We performed a retrospective cohort study of pediatric patients under 18 years of age who received autografting for the treatment of burns at our institution between 2017 and 2023. We compared ASTSG secured with fibrin sealant to those managed traditionally with sutures or staples. Outcomes of interest include the need for return trips to the operating room (OR), time to wound healing, graft take, and total time in the operating room. RESULTS: 83 patients underwent a total of 142 individual ASTSGs for management of unique body area injuries. 66.3 % were male, median age was 79 months, and scald was the most common mechanism of injury (41.0 %). Forty-five (39.5 %) traditionally affixed ASTSG required at least one return to the OR while only one (3.6 %) ASTSG secured with fibrin sealant required an additional return to the OR (p < 0.001). Graft take was similar in both groups (92.9 % for fibrin sealant vs. 93.9 % for traditional methods, p = 1). Time to wound healing was also similar: 16 vs. 15 days for fibrin glue and traditional methods, respectively (p = 0.23). CONCLUSION: Outcomes from autograft fixation with fibrin sealant were comparable to those treated with traditional methods, with a reduction in the need for return trips to the operating room. These data suggest that fibrin sealant is a suitable alternative to traditional fixation methods in pediatric autografting.

Endothelial monocyte activating polypeptide II interferes with VEGF-induced proangiogenic signaling.

Endothelial monocyte activating polypeptide II (EMAP II) is a proinflammatory cytokine with antiangiogenic properties. EMAP II functions as a potent inhibitor of primary and metastatic tumor growth, has strong inhibitory effects on endothelial cells (ECs), and can reduce intratumoral expression of the angiogenesis inducer vascular endothelial growth factor (VEGF). VEGF influences EC functions such as proliferation, migration, survival and tube formation. Therapeutic strategies that target VEGF have been demonstrated to reduce the tumor growth. We investigated the effects of EMAP II on VEGF-induced angiogenesis signaling. Primary human fetal lung ECs (HFLECs) and human umbilical vein ECs (HUVECs) were grown in E-Stim medium. Protein binding was analyzed using enzyme-linked immunosorbent assay (ELISA). Protein expression was determined by western blot analysis. EC proliferation and migration was determined using WST-1 reagent and transwell membrane, respectively. EMAP II efficiently and dose dependently binds to VEGF receptor 1 (VEGFR1) and VEGF receptor 2 (VEGFR2) as observed by ELISA. B(max) values for VEGFR1 and VEGFR2 were 0.45 and 0.17, respectively. In addition, EMAP II inhibited binding of VEGF to VEGFR1 and VEGFR2. EMAP II significantly reduced VEGF-induced expression of phosphorylated VEGFR1 (in HFLEC and HUVEC) by >50%, and of phosphorylated VEGFR2 (in HUVEC) by 66%. EMAP II also inhibited downstream VEGF signaling. Although VEGF-induced phosphorylation of Akt, Erk1/2, p38 and Raf 2.8-, 1.5-, 2.2- and 3.6-fold, respectively, EMAP II preincubation blocked this induction in phosphorylation to control levels. VEGF-induced EC proliferation 2.5-fold, and EMAP II pretreatment abrogated this effect. Similarly, VEGF-induced EC migration (2.5-fold) was significantly inhibited by EMAP II. These finding suggest that inhibition of VEGF signaling is one possible antiangiogenic mechanism of EMAP II, which may explain its in vivo antitumor activity and delineate therapeutic strategies to enhance anti-VEGF therapy to inhibit tumor growth.

Extrapulmonary sequestration with a left internal thoracic arterial feeding vessel in an infant treated with video-assisted Thoracoscopic resection: a case report.

BACKGROUND: Congenital lung malformations exist along a spectrum of pathogenesis and disease severity. Extrapulmonary sequestration (EPS), in which nonfunctional lung tissue develops without connection to the tracheobronchial tree, is one rare manifestation of this disease. Atypical vascular anatomy with a systemic feeding vessel characterizes these lesions. CASE PRESENTATION: A 3 day old, 37 week gestation infant underwent chest X-ray for confirmation of umbilical catheter placement and was found to have an elevated left hemidiaphragm consistent with eventration versus congenital diaphragmatic hernia. He remained asymptomatic and was evaluated as an outpatient at the age of 9 months, where CT angiogram demonstrated extrapulmonary versus intrapulmonary sequestration with a systemic feeding vessel from the left internal mammary artery. CONCLUSIONS: It is exceedingly rare for the feeding artery to arise from the internal mammary; two such cases have been reported to date, both in adult patients. Here we present a third case of EPS with arterial supply from the internal mammary successfully treated with video-assisted thoracoscopic resection in a 9 month old infant.

Extracorporeal cardiopulmonary resuscitation in a neonate after air embolism during insufflation for laparoscopic peritoneal dialysis catheter placement.

Laparoscopy is increasingly utilized in neonatal surgery with safe and effective outcomes. Air embolism from insufflation for pneumoperitoneum is a rare but known risk of laparoscopy. Here we present a rare case of air embolism during insufflation for laparoscopic peritoneal dialysis catheter placement treated with extracorporeal cardiopulmonary resuscitation.

Functional characterization of a putative aquaporin from Encephalitozoon cuniculi, a microsporidia pathogenic to humans.

The microsporidia are a group of obligate intracellular parasitic protists that have been implicated as both human and veterinary pathogens. The infectious process of these organisms is believed to be dependent upon the rapid influx of water into spores, presumably via aquaporins (AQPs), transmembrane channels that facilitate osmosis. An AQP-like sequence of the microsporidium Encephalitozoon cuniculi (EcAQP), when cloned and expressed in oocytes of Xenopus laevis, rendered these oocytes highly permeable to water. No permeability to the solutes glycerol or urea was observed. Pre-treatment of EcAQP-expressing oocytes with HgCl(2) failed to inhibit their osmotic permeability, as predicted from EcAQP's lack of mercury-sensitive cysteine residues near the NPA motifs which line the AQP aqueous pore. EcAQP exhibits sequence identity to AQP A of Dictyostelium discoideum (26%) and human AQP 2 (24%). Further study of AQPs in microsporidia and their potential inhibitors may yield novel therapeutic agents for microsporidian infections.

Are Immune Modulating Single Nucleotide Polymorphisms Associated with Necrotizing Enterocolitis?

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this study is to determine if functional single nucleotide polymorphisms (SNPs) in immune-modulating genes pre-dispose infants to NEC. After Institutional Review Board approval and parental consent, buccal swabs were collected for DNA extraction. TaqMan allelic discrimination assays and BglII endonuclease digestion were used to genotype specific inflammatory cytokines and TRIM21. Statistical analysis was completed using logistic regression. 184 neonates were analyzed in the study. Caucasian neonates with IL-6 (rs1800795) were over 6 times more likely to have NEC (p = 0.013; OR = 6.61, 95% CI 1.48-29.39), and over 7 times more likely to have Stage III disease (p = 0.011; OR = 7.13, (95% CI 1.56-32.52). Neonates with TGFß-1 (rs2241712) had a decreased incidence of NEC-related perforation (p = 0.044; OR = 0.28, 95% CI: 0.08-0.97) and an increased incidence of mortality (p = 0.049; OR = 2.99, 95% CI: 1.01 - 8.86). TRIM21 (rs660) was associated with NEC-related intestinal perforation (p = 0.038; OR = 4.65, 95% CI 1.09-19.78). In premature Caucasian neonates, the functional SNP IL-6 (rs1800795) is associated with both the development and increased severity of NEC. TRIM21 (rs660) and TGFß-1 (rs2241712) were associated with NEC- related perforation in all neonates in the cohort. These findings suggest a possible genetic role in the development of NEC.

Genomics in premature infants: a non-invasive strategy to obtain high-quality DNA.

We used a cost-effective, non-invasive method to obtain high-quality DNA from buccal epithelial-cells (BEC) of premature infants for genomic analysis. DNAs from BEC were obtained from premature infants with gestational age ≤ 36 weeks. Short terminal repeats (STRs) were performed simultaneously on DNA obtained from the buccal swabs and blood from the same patient. The STR profiles demonstrated that the samples originated from the same individual and exclude any contamination by external DNAs. Whole exome sequencing was performed on DNAs obtained from BEC on premature infants with and without necrotizing enterocolitis, and successfully provided a total number of reads and variants corroborating with those obtained from healthy blood donors. We provide a proof of concept that BEC is a reliable and preferable source of DNA for high-throughput sequencing in premature infants.