Statewide Hospital Admissions for Adult Survivors of Infant Surgical Diseases Over a 10-Y Period.

INTRODUCTION: The number of patients with congenital disease living to adulthood continues to grow. Often undergoing surgical correction in infancy, they continue to require lifelong care. Their numbers are largely unknown. We sought to evaluate hospital admissions of adult patients with esophageal atresia with tracheoesophageal fistula (EA/TEF), congenital diaphragmatic hernia (CDH), and Hirschsprung disease (HD). METHODS: The Florida Agency for Healthcare Administration inpatient database was merged with the Distressed Communities Index and Centers for Medicare and Medicaid Services Hospital and Physician Compare datasets. The dataset was queried for adult patients (≥18 y, born after 1970) with EA/TEF, CDH, and HD in their problem list from 2010 to 2020. Patient demographics, hospitalization characteristics, and discharge information were obtained. RESULTS: In total, 1140 admissions were identified (266 EA/TEF, 135 CDH, 739 HD). Patients were mostly female (53%), had a mean age of 31.6 y, and often admitted to an adult internist in a general hospital under emergency. Principal diagnoses and procedures (when performed) varied with diagnosis and age at admission. EA patients were admitted with dysphagia and foregut symptoms and often underwent upper endoscopy with dilation. CDH patients were often admitted for diaphragmatic hernias and underwent adult diaphragm repair. Hirschsprung patients were often admitted for intestinal obstructive issues and frequently underwent colonoscopy but trended toward operative intervention with increasing age. CONCLUSIONS: Adults with congenital disease continue to require hospital admission and invasive procedures. As age increases, diagnoses and performed procedures for each diagnoses evolve. These data could guide the formulation of multispecialty disease-specific follow-up programs for these patients.

Golf cart injuries have similar severity to all-terrain vehicle injuries in children: a multicenter comparison over a 5-year period.

Background: Golf carts (GCs) and all-terrain vehicles (ATVs) are popular forms of personal transport. Although ATVs are considered adventurous and dangerous, GCs are perceived to be safer. Anecdotal experience suggests increasing numbers of both GC and ATV injuries, as well as high severity of GC injuries in children. This multicenter study examined GC and ATV injuries and compared their injury patterns, resource utilization, and outcomes. Methods: Pediatric trauma centers in Florida submitted trauma registry patients age <16 years from January 2016 to June 2021. Patients with GC or ATV mechanisms were identified. Temporal trends were evaluated. Injury patterns, resource utilization, and outcomes for GCs and ATVs were compared. Intensive care unit admission and immediate surgery needs were compared using multivariable logistic regression. Results: We identified 179 GC and 496 ATV injuries from 10 trauma centers. GC and ATV injuries both increased during the study period (R2 0.4286, 0.5946, respectively). GC patients were younger (median 11 vs 12 years, p=0.003) and had more intracranial injuries (34% vs 19%, p<0.0001). Overall Injury Severity Score (5 vs 5, p=0.27), intensive care unit (ICU) admission (20% vs 16%, p=0.24), immediate surgery (11% vs 11%, p=0.96), and mortality (1.7% vs 1.4%, p=0.72) were similar for GCs and ATVs, respectively. The risk of ICU admission (OR 1.19, 95% CI 0.74 to 1.93, p=0.47) and immediate surgery (OR 1.04, 95% CI 0.58 to 1.84, p=0.90) remained similar on multivariable logistic regression. Conclusions: During the study period, GC and ATV injuries increased. Despite their innocuous perception, GCs had a similar injury burden to ATVs. Heightened safety measures for GCs should be considered. Level of evidence: III, prognostic/epidemiological.

Social determinants of health in pediatric trauma: Associations with injury mechanisms and outcomes in the context of the COVID-19 pandemic.

BACKGROUND: Relationships between social determinants of health and pediatric trauma mechanisms and outcomes are unclear in context of COVID-19. METHODS: Children <16 years old injured between 2016 and 2021 from ten pediatric trauma centers in Florida were included. Patients were stratified by high vs. low Social Vulnerability Index (SVI). Injury mechanisms studied were child abuse, ATV/golf carts, and firearms. Mechanism incidence trends and mortality were evaluated by interrupted time series and multivariable logistic regression. RESULTS: Of 19,319 children, 68% and 32% had high and low SVI, respectively. Child abuse increased across SVI strata and did not change with COVID. ATV/golf cart injuries increased after COVID among children with low SVI. Firearm injuries increased after COVID among children with high SVI. Mortality was predicted by injury mechanism, but was not independently associated with SVI, race, or COVID. CONCLUSION: Social vulnerability influences pediatric trauma mechanisms and COVID effects. Child abuse and firearm injuries should be targeted for prevention.

Language Differences by Race on Letters of Recommendation for the Pediatric Surgery Match.

OBJECTIVE: This study aims to evaluate if there is any significant linguistic difference in LoR based on applicant's race/ethnicity. DESIGN: Retrospective review of applications to pediatric surgery fellowship at a single institution (2016-2020). Race was self-reported by applicants. LoR were analyzed via the Linguistic Inquiry and Word Count (LIWC) software program. SETTING: Johns Hopkins All Children's Hospital, St. Petersburg, Florida USA. A free-standing tertiary pediatric hospital. PARTICIPANTS: Pediatric surgery fellowship applicants from 2016 to 2020. RESULTS: A total of 1086 LoR from 280 applicants (52% female) were analyzed. Racial distribution was Caucasians 62.1%, Asian 12.1%, Hispanics 7.1%, multiracial 6.4% African Americans 5%, and other/unknown 7.1%. Letter writers were largely male (84%), pediatric surgeons (63%) and professors (57%). There was no difference in LoR word count across races. LoR for female multiracial candidates contained higher use of affiliation and negative emotion terms compared to Hispanic females (p = 0.002 and 0.048, respectively), and past focus terms when compared to Caucasian and Asian female applicants (p < 0.001 and p = 0.003, respectively). Religion terms were more common in LoR for Asian females when compared to Caucasian females (p < 0.001). CONCLUSION: This study demonstrates linguistic differences in LoR for pediatric surgery training programs based on applicant race/ethnicity. While differences are present, these do not suggest overt bias based on applicants race or ethnicity.

Efficacy of Videoconference Interviews in the Pediatric Surgery Match.

PURPOSE: The pediatric surgery match is highly competitive with the interview process requiring significant resources. The purpose of this study was to evaluate the efficacy of videoconference interviewing (VI) as a screening tool in the pediatric surgery match process. METHODS: During the 2017 interview season, applicants participated in VI prior to on-site interviews. Applicants and faculty completed 15 and 8-question surveys, respectively, regarding their experiences. RESULTS: Both faculty and applicants agreed VI was easily workable and allowed them to accurately represent themselves. Faculty agreed VI would change how they rank candidates and that it is a helpful screening tool. Most disagreed VI could substitute for on-site interviews. Most applicants reported the cost and time required for on-site interviews was a hardship. Overall, applicants moved an average of 5.5 ± 2.9 (median 3) positions from the pre-VI to post-VI rank list. Thirty-seven percent of applicants moved out of the top ten rank list following VI. Of the lowest 5 applicants on the post-VI rank list, only 20% matched successfully. CONCLUSION: The pediatric surgery match requires a significant investment of time and money that creates a hardship for most applicants. VI may be an effective screening tool that could potentially reduce on-site interviews and alleviate the burden on applicants and general surgery training programs.

A ductus remnant confounding the diagnosis of blunt thoracic aortic injury in a 13-year-old adolescent boy.

Anatomical variants can pose diagnostic dilemmas for the clinician and may confound critical decision making for traumatic thoracic aortic injuries. With significant morbidity and mortality for both the injury and the therapeutic options in the pediatric population, an accurate diagnosis is essential for a good outcome. Knowledge of both the anatomical variant as well as the potential injury is required for a precise diagnosis. Highlighting these concepts, we present the case of a 13-year-old trauma patient with a possible blunt thoracic aortic injury. A suspected intimal aortic tear on computed tomography angiography proved to be a ductus remnant, which did not require intervention.

Mullerian inhibiting substance inhibits invasion and migration of epithelial cancer cell lines.

OBJECTIVE: Given the fact that Mullerian Inhibiting Substance (MIS) causes complex remodeling of the urogenital ridge and regression of the Mullerian ducts during male embryonic development, we examined whether MIS could affect similar cell properties such as migration and invasion that could contribute ultimately to micro-metastasis of cancers arising from Mullerian tissues. MIS receptor expressing cell lines found to be invasive and migratory in vivo are examined in an in vivo assay that is cost-effective. METHODS: We designed in vitro and in vivo experiments to determine if MIS inhibited the movement of cancer lines IGROV-1, HEp3, MDA-MB-231, and HT1080 in cell culture invasion/migration chamber assays and in chick embryo metastasis assays. RESULTS: MIS, at concentrations below those that inhibit cell proliferation, blocked in vitro invasion and in vivo migration of epithelial cancer cells that express the MIS receptor. CONCLUSIONS: While our laboratory has previously established MIS as an inhibitor of cancer cell proliferation using in vitro assays and in vivo xenografts, we now show that MIS can also inhibit in vivo tumor migration.

Mullerian inhibiting substance preferentially inhibits stem/progenitors in human ovarian cancer cell lines compared with chemotherapeutics.

Cancer stem cells are proposed to be tumor-initiating cells capable of tumorigenesis, recurrence, metastasis, and drug resistance, and, like somatic stem cells, are thought to be capable of unlimited self-renewal and, when stimulated, proliferation and differentiation. Here we select cells by expression of a panel of markers to enrich for a population with stem cell-like characteristics. A panel of eight was initially selected from 95 human cell surface antigens as each was shared among human ovarian primary cancers, ovarian cancer cell lines, and normal fimbria. A total of 150 combinations of markers were reduced to a panel of three--CD44, CD24, and Epcam--which selected, in three ovarian cancer cell lines, those cells which best formed colonies. Cells expressing CD44, CD24, and Epcam exhibited stem cell characteristics of shorter tumor-free intervals in vivo after limiting dilution, and enhanced migration in invasion assays in vitro. Also, doxorubicin, cisplatin, and paclitaxel increased this enriched population which, conversely, was significantly inhibited by Müllerian inhibiting substance (MIS) or the MIS mimetic SP600125. These findings demonstrate that flow cytometry can be used to detect a population which shows differential drug sensitivity, and imply that treatment of patients can be individualized to target both stem/progenitor cell enriched and nonenriched subpopulations. The findings also suggest that this population, amenable to isolation by flow cytometry, can be used to screen for novel treatment paradigms, including biologic agents such as MIS, which will improve outcomes for patients with ovarian cancer.

Uterine leiomyomas exhibit fewer stem/progenitor cell characteristics when compared with corresponding normal myometrium.

Uterine leiomyomas (also known as uterine fibroids) are the most common benign tumors of female reproductive tract and are the single most common indication for hysterectomies. Despite their high prevalence, the exact pathogenesis of these benign tumors is still unknown. One possible mechanism for leiomyoma formation is dysregulation of mesenchymal stem cell activity. Mesenchymal stem cells have been identified in both human and murine uteri and cancer stem cells have been identified in female reproductive malignancies. We compared stem/progenitor cell characteristics in both normal myometrium and the corresponding leiomyoma of patient's undergoing hysterectomies. We found that leiomyoma cells form fewer mesenchymal stem cell colonies and exhibit less Hoechst dye-excluding side population (SP) activity, which is a function associated with progenitor cells in other tissues, than cells isolated from normal myometrium. Whereas in normal myometrium, we observed heterogeneous expression of CD90, a cell surface marker associated the with differentiation potential of uterine fibroblasts, in leiomyomas, we observed homogenous expression of CD90, suggesting leiomyoma cells are more terminally differentiated. Furthermore, we found that while leiomyoma cells could only produce CD90 expressing cells, both CD90+ and CD90- myometrial cells could reestablish their original heterogeneous CD90 profile when expanded in vitro. These results suggest that normal myometrium contains cells with stem/progenitor cell activities that are absent in leiomyomas.

Breast hamartomas in adolescent females.

Breast hamartomas are uncommon lesions that have not been extensively characterized in the adolescent population. A search of patient records at our institution over a 17-year period identified seven cases of breast hamartomas in patients less than 18 years of age. We examine and report the clinical, radiographic, and pathologic characteristics of these cases. Breast hamartomas present as painless, palpable masses in the adolescent population. Ultrasonography reveals a well-defined, solid, oval mass, similar to the more common fibroadenoma. Two of the patients underwent core needle biopsy for diagnosis as the only intervention with the remainder undergoing surgical excision. None of the patients had any complications from surgery. There was one recurrence 9 months after initial excision. Histologically, the hamartomas consisted of densely packed, enlarged lobules set within a fibrous stroma. Breast hamartomas are rare in the adolescent population. The clinical and radiographic features are similar to the more common fibroadenoma, but the pathologic findings are diagnostic. Recurrence can occur if excision is incomplete. Increased recognition and accurate diagnosis will improve our understanding of the natural history of these lesions.

Serum Müllerian Inhibiting Substance/anti-Müllerian hormone levels in patients with adult granulosa cell tumors directly correlate with aggregate tumor mass as determined by pathology or radiology.

OBJECTIVES: Granulosa cell tumors (GCTs) comprise 2-5% of ovarian tumors. Serum Müllerian Inhibiting Substance (MIS, also known as anti-Müllerian hormone, or AMH) levels have been validated as a marker of GCT recurrence and progression. There has been little correlation between serum MIS/AMH levels and several clinical parameters in GCTs, including tumor burden. We have performed a retrospective review correlating aggregate tumor mass as reported by pathologic examination or by radiology with serum MIS/AMH levels drawn on the date of examination. METHODS: We retrospectively identified 32 GCT patients at our institution over the last 15 years who had serum MIS/AMH measurements. Patients who had serum MIS/AMH measurements within three days of surgery or on the same day as abdominal computerized tomography scan (CT) or magnetic resonance imaging (MRI) were further evaluated. RESULTS: We found a significant direct correlation between patient serum MIS/AMH levels and gross aggregate tumor mass determined by pathology (slope=15.4+/-6.06, r=0.65, p<0.04) or by radiographic aggregate tumor mass for all data points identified (slope=0.07+/-0.03, r=0.33, p<0.04) and after correcting for selection bias (slope=1.45+/-0.17, r=0.93, p<0.01). We also identified a significant difference between serum MIS/AMH levels between samples drawn the same day as negative and positive abdominal CT or MRI scans (8.16+/-1.54 vs. 158.7+/-32.2 ng/ml, p<0.0001). CONCLUSIONS: These data indicate a significant direct correlation between serum MIS/AMH levels and both gross and radiographic aggregate tumor mass in GCT patients. Together with the current literature, the present data argue for a more prominent role for serum MIS/AMH in the management of GCTs.

Endovascular stenting of a penetrating axillary artery injury in a 14-year-old with 1-year follow-up.

In the management of pediatric trauma, certain principles that are practiced in children who have sustained injuries more commonly seen in adults are extrapolated from the adult trauma literature. The increased use of computer tomography angiograms in the diagnosis of penetrating vascular trauma and endovascular therapy in treating vascular trauma in the adult population is being extended to the pediatric population. We present a case of a 14-year-old male with an axillary artery injury that was diagnosed by computer tomography angiogram and treated with an endovascular Stent graft with 1-year follow-up.

A 16-year-old male with gynecomastia and ductal carcinoma in situ.

While gynecomastia is common in adolescents, male breast cancer in the pediatric population is exceedingly rare. Occasional reports describe malignant and pre-malignant lesions in mastectomy specimens for gynecomastia in young adults. We present a 16-year-old male with unilateral gynecomastia discovered to have ductal carcinoma in situ (DCIS), treated by mastectomy with 4 year follow-up.

Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor cell characteristics.

Ovulation induces cyclic rupture and regenerative repair of the ovarian coelomic epithelium. This process of repeated disruption and repair accompanied by complex remodeling typifies a somatic stem/progenitor cell-mediated process. Using BrdU incorporation and doxycycline inducible histone2B-green fluorescent protein pulse-chase techniques, we identify a label-retaining cell population in the coelomic epithelium of the adult mouse ovary as candidate somatic stem/progenitor cells. The identified population exhibits quiescence with asymmetric label retention, functional response to estrous cycling in vivo by proliferation, enhanced growth characteristics by in vitro colony formation, and cytoprotective mechanisms by enrichment for the side population. Together, these characteristics identify the label-retaining cell population as a candidate for the putative somatic stem/progenitor cells of the coelomic epithelium of the mouse ovary.

Primary pulmonary rhabdomyosarcoma in a 5-month-old boy: a case report.

Primary pulmonary rhabdomyosarcoma (RMS) in the pediatric population is a rare entity. A 5-month-old boy initially treated for pneumonia was proven to have a primary pulmonary RMS, which was resected via thoracotomy. After a course of chemotherapy following the Children's Oncology Group low-risk RMS protocol (ARST0331), a restaging chest computerized tomography scan showed local recurrence, which was also resected by open thoracotomy. The patient is currently undergoing local radiotherapy and salvage chemotherapy regimen. This patient is the youngest reported to date with this entity. The prognostic significance of his young age and the morphologic findings of his tumor are unclear.

Adult mouse myometrial label-retaining cells divide in response to gonadotropin stimulation.

Conditional deletion of beta-catenin in the Müllerian duct mesenchyme results in a degenerative uterus characterized by replacement of the myometrial smooth muscle with adipose tissue. We hypothesized that the mouse myometrium houses somatic smooth muscle progenitor cells that are hormonally responsive and necessary for remodeling and regeneration during estrous cycling and pregnancy. We surmise that the phenotype observed in beta-catenin conditionally deleted mice is the result of dysregulation of these progenitor cells. The objective of this study was to identify the mouse myometrial smooth muscle progenitor cell and its niche, define the surface marker phenotype, and show a functional response of these cells to normal myometrial cycling. Uteri were labeled with 5-bromo-2'-deoxyuridine (BrdU) and chased for up to 14 weeks. Myometrial label-retaining cells (LRCs) were observed in the myometrium and stroma throughout the chase period. After 12 weeks, phenotypic analysis of the LRCs by immunofluorescence demonstrated that the majority of LRCs colocalized with alpha-smooth muscle actin, estrogen receptor-alpha, and beta-catenin. Flow cytometry of myometrial cells identified a myometrial Hoechst 33342 effluxing "side population" that expresses MISRII-Cre-driven YFP. Functional response of LRCs was investigated by human chorionic gonadotropin stimulation of week 12 chase mice and demonstrated sequential proliferation of LRCs in the endometrial stroma, followed by the myometrium. These results suggest that conventional myometrial regeneration and repair is executed by hormonally responsive stem or progenitor cells derived from the Müllerian duct mesenchyme. Disclosure of potential conflicts of interest is found at the end of this article.