Needle fetal thoracoscopy: a technique to assist with ultrasound-guided placement of challenging thoracoamniotic shunts.

INTRODUCTION: Fetal thoracoamniotic shunts are common lifesaving interventions but frequently require replacement. Needle fetal thoracoscopy is a technique that uses standard thoracoamniotic shunt introducer sheaths to permit direct visualization and even instrument manipulation during shunt deployment to facilitate optimal positioning and primary shunt function in the most challenging cases. CASE PRESENTATION: In this study, five patients who underwent needle fetal thoracoscopy-assisted thoracoamniotic shunt placement were reviewed. Three patients with large, macrocystic congenital pulmonary airway malformations (CPAM) with evidence of worsening mediastinal shift and/or hydrops and two patients with large chylothorax with fetal hydrops were treated. Four cases had previous shunts that failed due to poor sonographic visualization during initial placement, cyst septations, shunt obstruction or dislodgment. Needle fetal thoracoscopy was used to disrupt cyst walls and septations, clear hematoma, and confirm optimal initial position of the shunt. In this series, one severe CPAM patient with short cervix developed preterm labor postoperatively resulting in neonatal demise. The remaining four patients experienced resolution of hydrops and progressed to successful delivery with excellent neonatal outcomes. CONCLUSION: Needle fetal thoracoscopy is a procedure that may be selectively deployed in challenging thoracoamniotic shunt cases impacted by recurrent failure, poor sonographic windows, and challenging fetal positioning.

Successful Use of Acellular Small Intestinal Submucosa Graft in Vaginal Reconstruction.

PURPOSE: Various techniques for neovaginal construction have been employed in the pediatric and adult populations, including the use of intestinal segments, buccal mucosal grafts, and skin grafts. Small intestinal submucosa (SIS) extracellular matrix grafts have been described as a viable alternative, though prior experience is limited. Our purpose was to assess operative characteristics and patient outcomes with neovaginal construction using SIS grafts. METHODS: Thirteen patients underwent vaginoplasty with acellular porcine SIS grafts at our institution between 2018 and 2022. Operative and clinical data, postoperative mold management, vaginal dilating length, and complications were reviewed. RESULTS: Age at time of repair ranged from 13 to 30 years (median 19 years). Patient diagnosis included cloacal anomalies (n = 4), Mayer-Rokitansky-Küster-Hauser syndrome (n = 4), isolated vaginal atresia with or without a transverse vaginal septum (n = 4), and vaginal rhabdomyosarcoma requiring partial vaginectomy (n = 1). Following dissection of the neovaginal space, a silicon mold wrapped with SIS graft was placed with retention sutures and removed on postoperative day 7. Median (IQR) operative time was 171 (118-192) minutes, estimated blood loss was 10 (5-20) mL, and length of stay was 2 (1-3) days. The follow-up period ranged from 3 to 47 months (median 9 months). Two patients developed postoperative vaginal stenosis that resolved with dilation under anesthesia. Mean vaginal length on latest follow-up was 8.97 cm. All thirteen patients had successful engraftment and progressed to performing self-dilations or initiating intercourse to maintain patency. There were no cases of graft reaction or graft extrusion. CONCLUSIONS: We conclude that acellular small intestinal submucosa grafts are effective and safe alternatives for mold coverage in neovaginal construction. Our experience demonstrates minimal perioperative morbidity, early mold removal, and progression to successful dilation with maintenance of a functional vaginal length. Future study on sexual outcomes, patient satisfaction, and comparison against alternative techniques has been initiated. LEVEL OF EVIDENCE: IV. TYPE OF STUDY: Retrospective Study.

Ex-Utero Intrapartum Treatment-to-Airway for Obstructing Fetal Neck Masses: A Singular Methodology for Monochorionic and Dichorionic Twin Pregnancies.

Fetal airway obstruction in one twin of a diamniotic pregnancy presents unique challenges. Very few cases of ex-utero-intrapartum-treatment (EXIT) procedures for twin pregnancy have been reported and only in dichorionic pregnancies. We report a singular methodology for EXIT-to-airway procedures in two pregnancies involving monochorionic and dichorionic twins. Two cases of EXIT-to-airway in twin pregnancies were performed in 2018 and 2019 at a regional fetal treatment center. Case 1 involved a giant cervical teratoma in a monochorionic-diamniotic twin pregnancy with preterm labor at 29 weeks. Case 2 involved a dichorionic-diamniotic pregnancy with a large cervical lymphatic malformation with preterm labor at 36 weeks. In each case, the polyhydramnios caused the affected twin's amniotic sac to be the presenting sac for the surgical approach. Bronchoscopy and successful intubation was completed after 22 and 10 minutes of uteroplacental bypass, respectively. The bystander twins were delivered second without intubation and resuscitated without perinatal distress. EXIT-to-airway appears to be a reasonable option for twins including monochorionic pregnancies, via delivery of the affected twin first followed by delivery of the bystander twin. Thoughtful preparation and counseling by an experienced multidisciplinary team permits an EXIT-to-airway approach for twin pregnancies even in an emergent setting.

Association of Prophylactic Antibiotics With Early Infectious Complications in Children With Cancer Undergoing Central Venous Access Device Placement.

OBJECTIVE: To evaluate the impact of prophylactic antibiotics on early infectious complications after central venous access device (VAD) placement in children with cancer. SUMMARY OF BACKGROUND DATA: Despite the frequency of VAD procedures in children, the effectiveness of prophylactic antibiotics for reducing infectious complications is unknown. METHODS: This was a retrospective cohort study of children with cancer undergoing central VAD placement identified in the Pediatric Health Information System database between 2017-2021. The primary outcome was the rate of early infectious complications (composite surgical site infections, central line-associated bloodstream infections, and bacteremia). Multivariable logistic regression was used to evaluate factors associated with early infection, and heterogeneity of treatment effect of prophylactic antibiotics was compared across subgroups. RESULTS: 9,216 patients were included (6,058 ports and 3,158 tunneled lines). Prophylactic antibiotics were associated with lower early infectious complications overall (1.3% vs. 2.4%; OR 0.55 [95% C.I. 0.39-0.79], P<0.001), an effect demonstrated for tunneled lines (OR 0.59, 95% C.I.: 0.41-0.84) but not ports (OR 3.01, 95% C.I.: 0.66-13.78). On multivariate analysis, prophylactic antibiotics (OR 0.67, 95% C.I.: 0.45-0.97) and solid tumors (OR 0.38, 95% C.I.: 0.22-0.64) were associated with reduced odds of early infections, while tunneled lines (OR 20.78, 95% C.I.: 9.83-43.93) and acute myelogenous leukemia (OR 2.37, 95% C.I.: 1.58-3.57) had increased odds. CONCLUSIONS: Prophylactic antibiotics are associated with reduced early infectious complications after central VAD placement overall. Despite recommendations from multiple national organizations against prophylactic antibiotics, these findings suggest a benefit in children with malignancy undergoing tunneled line placement.

Innovation versus Experimentation: An Application of Ethical Frameworks to the Acceptance of Fluorescence-Guided Pediatric Surgery.

Innovation is essential to the advancement of the field of pediatric surgery. The natural skepticism toward new technologies in pediatrics leads to frequent confusion of surgical innovation and research. Using fluorescence-guided surgery as an archetype for this ethical discussion, we apply existing conceptual frameworks of surgical innovation to understand the distinction between innovation and experimentation, acknowledging the spectrum and "grey zone" in between. In this review, we discuss the role of Institutional Review Boards in evaluating surgical practice innovations, and the aspects of certain surgical innovations that are distinct from experimentation, including a thorough understanding of the risk profile, preexisting use in humans, and adaptation from related fields. Examining fluorescence-guided surgery through these existing frameworks as well as the concept of equipoise, we conclude that new applications of indocyanine green do not constitute human subjects research. Most importantly, this example gives practitioners a lens through which they may appraise potential surgical innovations to allow for a sensible and efficient improvement of the field of pediatric surgery. LEVEL OF EVIDENCE: V.

Delivering mRNAs to mouse tissues using the SEND system.

mRNAs produced in a cell are almost always translated within the same cell. Some mRNAs are transported to other cells of the organism through processes involving membrane nanotubes or extracellular vesicles. A recent report describes a surprising new phenomenon of encapsulating mRNAs inside virus-like particles (VLPs) to deliver them to other cells in a process that was named SEND (Selective Endogenous eNcapsidation for cellular Delivery). Although the seminal work demonstrates the SEND process in cultured cells, it is unknown whether this phenomenon occurs in vivo . Here, we demonstrate the SEND process in living organisms using specially designed genetically engineered mouse models. Our proof of principle study lays a foundation for the SEND-VLP system to potentially be used as a gene therapy tool to deliver therapeutically important mRNAs to tissues.

CD4 and IL-2 mediated NK cell responses after COVID-19 infection and mRNA vaccination in adults.

A detailed understanding of protective immunity against SARS-CoV-2 is incredibly important in fighting the pandemic. Central to protective immunity is the ability of the immune system to recall previous exposures. Although antibody and T cell immunity have gained considerable attention, the contribution of the NK cell compartment to immune recall and protection from SARS-CoV-2 has not been explored. In this study, we investigate the NK cell responses to stimulation with SARS-CoV-2 in previously exposed and non-exposed individuals. We show that NK cells demonstrate an enhanced CD4+ T cell dependent response when re-exposed to SARS-CoV-2 antigen. The enhanced response is dependent on T cells and correlates with the number of SARS-CoV-2 specific CD4 T cells. We find that IL-2 is a critical mediator of NK cell function. These findings suggest that NK cells contribute to the protective responses against SARS-CoV-2 through a cooperation with antigen-specific CD4 T cells and have significant implications on our understanding of protective immunity in SARS-CoV-2.

Weight gain and resource utilization in infants after fundoplication versus gastrojejunostomy.

PURPOSE: There is wide practice variation in the use of laparoscopic fundoplication (LF) versus gastrojejunostomy (GJ) tube insertion for children who do not tolerate gastric feeds. Using weight gain as an objective proxy of adequate nutrition, we sought to evaluate the difference in weight gain between LF and GJ. METHODS: A retrospective, cohort study was conducted of patients ≤ 2 years who underwent LF or GJ between 2014 and 2019 at a single institution. Patient characteristics, change in weight 1-year post-procedure and frequency of unplanned healthcare utilization encounters were collected and examined. RESULTS: A total of 125 patients (50.4%LF, 49.6%GJ) were identified. Adjusted modeling demonstrated that on average, there was an additional 0.85-unit increase in weight-for-age Z scores in the LF compared to the GJ cohort (p = 0.01). The GJ cohort had significantly more unplanned healthcare utilization encounters (4.2, SD 3.4) compared to LF (3.0, SD 3.1) (p = 0.03). Furthermore, the GJ cohort underwent an average of 3.3 planned GJ exchanges within 1-year post-procedure. CONCLUSION: In the first year post-operatively, LF is associated with increased weight gain and fewer unplanned and overall healthcare encounters compared to GJ. Long-term outcomes including weight gain and quality-of-life measures should be studied to develop standardized guidelines for this common clinical scenario.

Timeliness of pediatric surgical appendicitis care is associated with time of hospital admission.

BACKGROUND: Despite the frequency of acute appendicitis in children, there is no evidence-based consensus surrounding the urgency of the operation if a diagnosis is made after regular business hours. Although a modest delay in time to operation does not increase disease severity, postponing cases to the next calendar day may be associated with higher resource utilization. We aimed to evaluate the trend of delaying appendectomies to the next calendar day and its associated outcomes. METHODS: We queried the Pediatric Health Information System to analyze appendectomy patients younger than 18 y of age from 2010 to 2018. Same-day appendectomy and next-day appendectomy cohorts were created using admission hour and operative day. Healthcare cost, length of stay, surgical complications, and 30-day readmission rates were collected. Bivariate analyses and multivariable regressions were used to evaluate groups stratified by time of presentation. RESULTS: During the study period, 113,662 appendectomies were performed, comprising 88,715 (78.1%) same-day appendectomies and 24,947 (21.9%) next-day appendectomies. A higher proportion of same-day appendectomies (80.5%) were performed during hours 12:00am to 5:00pm and 19.5% were performed during hours 6:00pm to 11:00pm. The trend of next-day appendectomies increased during the study period from 13.9% to 20.2%. This was primarily evident in the 6:00pm to 11:00pm period. The 5:00pm cutoff was most predictive of a next-day appendectomy. Next-day appendectomies had similar rates of surgical complications; however, they were associated with higher costs, longer lengths of stay, and higher readmission rates. CONCLUSION: As the understanding of appendicitis urgency has changed, a more tempered approach of delivering surgical care has trended. Although short delays appear safe, postponement to the next calendar day is associated with higher resource utilization.

Trends in gastrostomy tube placement with concomitant Nissen fundoplication for infants and young children at Pediatric Tertiary Centers.

PURPOSE: In infants and toddlers, gastrostomy tube placement (GT) is typically accompanied by consideration of concomitant Nissen fundoplication (NF). Historically, rates of NF have varied across providers and institutions. This study examines practice variation and longitudinal trends in NF at pediatric tertiary centers. METHODS: Patients ≤ 2 years who underwent GT between 2008 and 2018 were identified in the Pediatric Health Information System database. Patient demographics and rates of NF were examined. Descriptive statistics were used to evaluate the variation in the proportion of GT with NF at each hospital, by volume and over time. RESULTS: 40,348 patients were identified across 40 hospitals. Most patients were male (53.8%), non-Hispanic white (49.5%) and publicly-insured (60.4%). Rates of NF by hospital varied significantly from 4.2 to 75.2% (p < 0.001), though were not associated with geographic region (p = 0.088). Rates of NF decreased from 42.8% in 2008 to 14.2% in 2018, with a mean annual rate of change of - 3.07% (95% CI - 3.53, - 2.61). This trend remained when stratifying hospitals into volume quartiles. CONCLUSION: There is significant practice variation in performing NF. Regardless of volume, the rate of NF is also decreasing. Objective NF outcome measurements are needed to standardize the management of long-term enteral access in this population.

Evaluation of adherence to the Commission on Cancer lung cancer quality measures.

OBJECTIVE: In this study we present historic data on adherence to and survival outcomes associated with recently introduced quality measures for the management of non-small-cell lung cancer. METHODS: The National Cancer Data Base was queried to identify all patients with non-small-cell lung cancer from 1998 to 2011. Adherence to guidelines was assessed for each of 3 Commission on Cancer-defined quality measures: (1) sampling 10 regional lymph nodes at surgery; (2a) surgery within 120 days of neoadjuvant chemotherapy or, (2b) 180 days of adjuvant chemotherapy; and (3) nonsurgical primary therapy in cN2 disease. The likelihood of measure adherence and the association of measure adherence with all-cause mortality were analyzed controlling for patient, hospital, and time period characteristics. RESULTS: Regional lymph node sampling was inadequate in 72.7% of cases. Only 28.7% began adjuvant chemotherapy within 180 days of surgery. However, 96.5% of patients who received neoadjuvant chemotherapy proceeded to surgery within 120 days and surgery was first-line treatment for cN2 disease in only 3.7% of patients. Uninsured or Medicaid status was an independent risk factor for a prolonged delay between neoadjuvant chemotherapy and surgery (odds ratio, 1.36; 95% confidence interval, 1.08-1.72) and surgery and adjuvant treatment (odds ratio, 1.92; 95% confidence interval, 1.69-2.19). Overall survival was significantly better in patients whose care conformed to quality standards for nodal sampling (measure 1), and timing of chemotherapy. CONCLUSIONS: Adherence rates for nodal sampling at the time of surgery and receipt of adjuvant chemotherapy were low. These findings highlight opportunities for improvement efforts, but more measures are needed to more broadly assess the quality of lung cancer care.

Impact of Decolonization Protocols and Recurrence in Pediatric MRSA Skin and Soft-Tissue Infections.

BACKGROUND: Methicillin-resistant staphylococcus aureus (MRSA) colonization is associated with the development of skin and soft-tissue infection in children. Although MRSA decolonization protocols are effective in eradicating MRSA colonization, they have not been shown to prevent recurrent MRSA infections. This study analyzed the prescription of decolonization protocols, rates of MRSA abscess recurrence, and factors associated with recurrence. MATERIALS AND METHODS: This study is a single-institution retrospective review of patients ≤18 y of age diagnosed with MRSA culture-positive abscesses who underwent incision and drainage (I&D) at a tertiary-care children's hospital. The prescription of an MRSA decolonization protocol was recorded. The primary outcome was MRSA abscess recurrence. RESULTS: Three hundred ninety-nine patients with MRSA culture-positive abscesses who underwent I&D were identified. Patients with previous history of abscesses, previous MRSA infection groin/genital region abscesses, higher number of family members with a history of abscess/cellulitis or MRSA infection, and I&D by a pediatric surgeon were more likely to be prescribed decolonization. Decolonized patients did not have lower rates of recurrence. Recurrence was more likely to occur in patients with previous abscesses, previous MRSA infection, family history of abscesses, family history of MRSA infection, Hispanic ethnicity, and those with fever on admission. CONCLUSIONS: MRSA decolonization did not decrease the rate of recurrence of MRSA abscesses in our patient cohort. Patients at high risk for MRSA recurrence such as personal or family history of abscess or MRSA infection, Hispanic ethnicity, or fever on admission did not benefit from decolonization.

Magnetic kyphoplasty: A novel drug delivery system for the spinal column.

Vertebral compression fractures (VCFs) caused by metastatic malignancies or osteoporosis are devastating injuries with debilitating outcomes for patients. Minimally invasive kyphoplasty is a common procedure used for symptomatic amelioration. However, it fails in treating the underlying etiologies of VCFs. Use of systemic therapy is limited due to low perfusion to the spinal column and systemic toxicity. Localized delivery of drugs to the vertebral column can provide a promising alternative approach. A porcine kyphoplasty model was developed to study the magnetically guided drug delivery of systemically injected magnetic nanoparticles (MNPs). Jamshidi cannulated pedicle needles were placed into the thoracic vertebra and, following inflatable bone tamp expansion, magnetic bone cement was injected to the vertebral body. Histological analysis was performed after intravenous injection of MNPs. Qualitative analysis of harvested tissues revealed successful placement of magnetic cement into the vertebral body. Further quantitative analysis of histological sections of several vertebral bodies demonstrated enhanced accumulation of MNPs to regions that had magnetic cement injected during kyphoplasty compared to those that did not. By modifying the kyphoplasty bone cement to include magnets, thereby providing a guidance stimulus and a localizer, we were successfully able to guide intravenously injected magnetic nanoparticles to the thoracic vertebra. These results demonstrate an in-vivo proof of concept of a novel drug delivery strategy that has the potential to treat the underlying causes of VCFs, in addition to providing symptomatic support.

Von Economo neurons of the anterior cingulate across the lifespan and in Alzheimer's disease.

BACKGROUND: Throughout the human aging lifespan, neurons acquire an unusually high burden of wear and tear; this is likely why age is considered the strongest risk factor for the development of Alzheimer's Disease (AD). Von Economo neurons (VENs) are rare, spindle-shaped cells mostly populated in anterior cingulate cortex. In a prior study, "SuperAgers" (individuals older than 80 years of age with outstanding memory ability) showed higher VEN densities compared to elderly controls with average memory, and those with amnestic Mild Cognitive Impairment (aMCI). The intrinsic vulnerabilities of these neurons are unclear, and their contribution to neurodegeneration is unknown. The current study investigated the influence of age and the severity of Alzheimer's disease (AD) on VEN density. METHODS: VEN and total neuronal densities were quantitated using unbiased stereological methods in the anterior cingulate cortex of postmortem samples from the following subject groups: younger controls (age 20-60), SuperAgers, cognitively average elderly controls (age 65+), individuals diagnosed antemortem with aMCI, and individuals diagnosed antemortem with dementia of AD (N = 5, per group). RESULTS: The AD group showed significantly lower VEN density compared to younger and older controls (p < .05), but not compared to the aMCI group, and VENs bearing neurofibrillary tangles were discovered in AD cases. The aMCI group showed lower VEN density than elderly controls, but this was not significant. There was a significant negative correlation between VEN density and Braak stages of AD (p < .001). Consistent with prior findings, SuperAgers showed highest mean VEN density, even when compared to younger cases. CONCLUSIONS: VENs in human anterior cingulate cortex are vulnerable to AD pathology, particularly in later stages of pathogenesis. Their densities do not change throughout aging in individuals with average cognition, and they are more numerous in SuperAgers.

Management of idiopathic spinal epidural lipomatosis: a case report and review of the literature.

BACKGROUND: Spinal epidural lipomatosis (SEL) is a rare pathologic growth of histologically normal unencapsulated adipose tissue in the epidural space. Although rare, SEL can compress the spinal cord or nerve roots causing myelopathy or radiculopathy. While SEL has been associated with long-term exposure to endogenous or exogenous steroids and obesity, idiopathic forms of SEL are much rarer. CASE REPORT: In this report, we present the first case of SEL isolated to the cervical region compressing the spinal cord in a healthy, non-obese, preadolescent patient. CONCLUSION: Idiopathic SEL in the pediatric population is a rare entity. This is the first case of epidural lipomatosis isolated to the cervical region in an adult or child patient. In refractory, symptomatic cases of idiopathic SEL, surgical decompression is often required.

Diabetes and morbid obesity are associated with higher reoperation rates following microvascular decompression surgery: An ACS-NSQIP analysis.

BACKGROUND: Microvascular decompression (MVD) is the preferred treatment for refractory trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia. Despite its high rate of success, MVD carries risk of complications. In this study, we examine outcomes following MVD and identify risk factors associated with adverse outcomes. METHODS: A review of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was performed with CPT code 61458 queried between 2007 and 2014. Demographics, preoperative comorbidities, and 30-day outcomes were analyzed. Univariate and multivariate regression analyses were performed to identify predictors of reoperation and adverse events. RESULTS: Five hundred and six craniotomies were studied. Nineteen (5.5%) instances of 30-day readmission were reported, with 14 (2.8%) patients returning to the operating room. No instances of death or hemorrhage requiring operation were reported. Morbid obesity (body mass index >40) (P = 0.030) and diabetes (P = 0.017) were associated with risk of reoperation. Age, operative time, and indication for surgery were not associated with significant differences in adverse events. CONCLUSIONS: MVD is a common and effective procedure with a relatively safe profile and low 30-day risk of reoperation. Advanced age is not associated with worse outcomes. Obesity and diabetes, however, are associated with increased risk of reoperation and may warrant additional precautions.

Morphometric and histologic substrates of cingulate integrity in elders with exceptional memory capacity.

This human study is based on an established cohort of "SuperAgers," 80+-year-old individuals with episodic memory function at a level equal to, or better than, individuals 20-30 years younger. A preliminary investigation using structural brain imaging revealed a region of anterior cingulate cortex that was thicker in SuperAgers compared with healthy 50- to 65-year-olds. Here, we investigated the in vivo structural features of cingulate cortex in a larger sample of SuperAgers and conducted a histologic analysis of this region in postmortem specimens. A region-of-interest MRI structural analysis found cingulate cortex to be thinner in cognitively average 80+ year olds (n = 21) than in the healthy middle-aged group (n = 18). A region of the anterior cingulate cortex in the right hemisphere displayed greater thickness in SuperAgers (n = 31) compared with cognitively average 80+ year olds and also to the much younger healthy 50-60 year olds (p < 0.01). Postmortem investigations were conducted in the cingulate cortex in five SuperAgers, five cognitively average elderly individuals, and five individuals with amnestic mild cognitive impairment. Compared with other subject groups, SuperAgers showed a lower frequency of Alzheimer-type neurofibrillary tangles (p < 0.05). There were no differences in total neuronal size or count between subject groups. Interestingly, relative to total neuronal packing density, there was a higher density of von Economo neurons (p < 0.05), particularly in anterior cingulate regions of SuperAgers. These findings suggest that reduced vulnerability to the age-related emergence of Alzheimer pathology and higher von Economo neuron density in anterior cingulate cortex may represent biological correlates of high memory capacity in advanced old age.