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1.
NAR Genom Bioinform ; 6(1): lqae006, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38312938

ABSTRACT

Visualizing spatial assay data in anatomical images is vital for understanding biological processes in cell, tissue, and organ organizations. Technologies requiring this functionality include traditional one-at-a-time assays, and bulk and single-cell omics experiments, including RNA-seq and proteomics. The spatialHeatmap software provides a series of powerful new methods for these needs, and allows users to work with adequately formatted anatomical images from public collections or custom images. It colors the spatial features (e.g. tissues) annotated in the images according to the measured or predicted abundance levels of biomolecules (e.g. mRNAs) using a color key. This core functionality of the package is called a spatial heatmap plot. Single-cell data can be co-visualized in composite plots that combine spatial heatmaps with embedding plots of high-dimensional data. The resulting spatial context information is essential for gaining insights into the tissue-level organization of single-cell data, or vice versa. Additional core functionalities include the automated identification of biomolecules with spatially selective abundance patterns and clusters of biomolecules sharing similar abundance profiles. To appeal to both non-expert and computational users, spatialHeatmap provides a graphical and a command-line interface, respectively. It is distributed as a free, open-source Bioconductor package (https://bioconductor.org/packages/spatialHeatmap) that users can install on personal computers, shared servers, or cloud systems.

2.
Eur J Cancer ; 180: 89-98, 2023 02.
Article in English | MEDLINE | ID: mdl-36566574

ABSTRACT

PURPOSE: The aim of this paper is to better define the clinical features and outcomes of young patients with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) with regional and distant lymph node (LN) metastases treated in a standardised fashion, we analysed LN involvement in COG study ARST0332, which evaluated a risk-based treatment strategy for young patients with all stages of NRSTS. PATIENTS AND METHODS: Patients <30 years old with newly diagnosed NRSTS and LN metastases enrolled on ARST0332 were studied. Regional LN sampling was required for those with epithelioid sarcoma, clear cell sarcoma or clinically/radiographically enlarged LNs. Tumour features and extent of pre-enrolment resection determined treatment, including chemotherapy, radiotherapy, and delayed surgery. Recommendations for LN metastases included LN dissection at the time of primary tumour resection and dose-adapted radiotherapy based on extent of LN resection. RESULTS: Twenty of 529 eligible and evaluable ARST0332 patients with NRSTS had LN metastases; epithelioid sarcoma had the highest incidence (18%, 5 of 28). Pre-treatment imaging identified LN enlargement in 19 of 20 patients; 1 had no pre-treatment LN imaging. At 6.9 years median follow-up for surviving patients, 5-year overall survival was 85.7% (95% CI: 33.4%, 97.9%) for seven patients with isolated LN metastases and 15.4% (95% CI: 2.5%, 38.8%) for 13 patients with additional extranodal metastases. LN recurrence occurred in only one patient without LNs sampled at initial diagnosis. CONCLUSION: LN metastases occur in about 4% of paediatric/young adult NRSTS, are limited to a few histologic subtypes, and are rare in patients who did not have clinical or imaging evidence of lymphadenopathy, suggesting that biopsies of non-enlarged LNs are not necessary to identify occult involvement. Patients with isolated LN metastases have high 5-year overall survival (∼85%) and should be treated with curative intent. GOV REGISTRY NO: NCT00346164.


Subject(s)
Rhabdomyosarcoma , Sarcoma , Soft Tissue Neoplasms , Adult , Child , Humans , Young Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphatic Metastasis , Sarcoma/pathology , Soft Tissue Neoplasms/pathology
3.
Nat Commun ; 13(1): 3057, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35650195

ABSTRACT

Desmoplastic small round cell tumor (DSRCT) is an aggressive, usually incurable sarcoma subtype that predominantly occurs in post-pubertal young males. Recent evidence suggests that the androgen receptor (AR) can promote tumor progression in DSRCTs. However, the mechanism of AR-induced oncogenic stimulation remains undetermined. Herein, we demonstrate that enzalutamide and AR-directed antisense oligonucleotides (AR-ASO) block 5α-dihydrotestosterone (DHT)-induced DSRCT cell proliferation and reduce xenograft tumor burden. Gene expression analysis and chromatin immunoprecipitation sequencing (ChIP-seq) were performed to elucidate how AR signaling regulates cellular epigenetic programs. Remarkably, ChIP-seq revealed novel DSRCT-specific AR DNA binding sites adjacent to key oncogenic regulators, including WT1 (the C-terminal partner of the pathognomonic fusion protein) and FOXF1. Additionally, AR occupied enhancer sites that regulate the Wnt pathway, neural differentiation, and embryonic organ development, implicating AR in dysfunctional cell lineage commitment. Our findings have direct clinical implications given the widespread availability of FDA-approved androgen-targeted agents used for prostate cancer.


Subject(s)
Androgen Receptor Antagonists , Desmoplastic Small Round Cell Tumor , Receptors, Androgen , Androgen Receptor Antagonists/pharmacology , Androgens , Animals , Cell Line, Tumor , Desmoplastic Small Round Cell Tumor/genetics , Humans , Male , Oligonucleotides, Antisense/pharmacology , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Xenograft Model Antitumor Assays
4.
NPJ Precis Oncol ; 6(1): 21, 2022 Apr 04.
Article in English | MEDLINE | ID: mdl-35379887

ABSTRACT

Desmoplastic small round cell tumor (DSRCT) is a highly aggressive soft tissue sarcoma that is characterized by the EWSR1-WT1 fusion protein. Patients present with hundreds of tumor implants in their abdominal cavity at various sites. To determine the genetic relatedness among these sites, exome and RNA sequencing were performed on 22 DSRCT specimens from 14 patients, four of whom had specimens from various tissue sites. Multi-site tumors from individual DSRCT patients had a shared origin and were highly related. Other than the EWSR1-WT1 fusion, very few secondary cancer gene mutations were shared among the sites. Among these, ARID1A, was recurrently mutated, which corroborates findings by others in DSRCT patients. Knocking out ARID1A in JN-DSRCT cells using CRISPR/CAS9 resulted in significantly lower cell proliferation and increased drug sensitivity. The transcriptome data were integrated using network analysis and drug target database information to identify potential therapeutic opportunities in EWSR1-WT1-associated pathways, such as PI3K and mTOR pathways. Treatment of JN-DSRCT cells with the PI3K inhibitor alpelisib and mTOR inhibitor temsirolimus reduced cell proliferation. In addition, the low mutation burden was associated with an immune-cold state in DSRCT. Together, these data reveal multiple genomic and immune features of DSRCT and suggest therapeutic opportunities in patients.

5.
JAMA Surg ; 157(4): 327-334, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35138327

ABSTRACT

IMPORTANCE: The lack of underrepresented in medicine physicians within US academic surgery continues, with Black surgeons representing a disproportionately low number. OBJECTIVE: To evaluate the trend of general surgery residency application, matriculation, and graduation rates for Black trainees compared with their racial and ethnic counterparts over time. DESIGN, SETTING, AND PARTICIPANTS: In this nationwide multicenter study, data from the Electronic Residency Application Service (ERAS) for the general surgery residency match and Graduate Medical Education (GME) surveys of graduating general surgery residents were retrospectively reviewed and stratified by race, ethnicity, and sex. Analyses consisted of descriptive statistics, time series plots, and simple linear regression for the rate of change over time. Medical students and general surgery residency trainees of Asian, Black, Hispanic or Latino of Spanish origin, White, and other races were included. Data for non-US citizens or nonpermanent residents were excluded. Data were collected from 2005 to 2018, and data were analyzed in March 2021. MAIN OUTCOMES AND MEASURES: Primary outcomes included the rates of application, matriculation, and graduation from general surgery residency programs. RESULTS: Over the study period, there were 71 687 applicants, 26 237 first-year matriculants, and 24 893 graduates. Of 71 687 applicants, 24 618 (34.3%) were women, 16 602 (23.2%) were Asian, 5968 (8.3%) were Black, 2455 (3.4%) were Latino, and 31 197 (43.5%) were White. Women applicants and graduates increased from 29.4% (1178 of 4003) to 37.1% (2293 of 6181) and 23.5% (463 of 1967) to 33.5% (719 of 2147), respectively. When stratified by race and ethnicity, applications from Black women increased from 2.2% (87 of 4003) to 3.5% (215 of 6181) (P < .001) while applications from Black men remained unchanged (3.7% [150 of 4003] to 4.6% [284 of 6181]). While the matriculation rate for Black women remained unchanged (2.4% [46 of 1919] to 2.3% [52 of 2264]), the matriculation rate for Black men significantly decreased (3.0% [57 of 1919] to 2.4% [54 of 2264]; P = .04). Among Black graduates, there was a significant decline in graduation for men (4.3% [85 of 1967] to 2.7% [57 of 2147]; P = .03) with the rate among women remaining unchanged (1.7% [33 of 1967] to 2.2% [47 of 2147]). CONCLUSIONS AND RELEVANCE: Findings of this study show that the underrepresentation of Black physicians at every stage in surgical training pipeline persists. Black men are especially affected. Identifying factors that address intersectionality and contribute to the successful recruitment and retention of Black trainees in general surgery residency is critical for achieving racial and ethnic as well as gender equity.


Subject(s)
Internship and Residency , Surgeons , Education, Medical, Graduate , Female , Humans , Intersectional Framework , Male , Retrospective Studies , Surgeons/education , United States
6.
Am Surg ; 88(1): 103-108, 2022 Jan.
Article in English | MEDLINE | ID: mdl-33375827

ABSTRACT

BACKGROUND: Fecal diversion after ileal pouch anal anastomosis (IPAA) in children with ulcerative colitis (UC) remains controversial. We hypothesize that a modified two-stage IPAA omitting diverting ileostomy (DI) after IPAA, found to be safe in adults, would produce similar results in children. METHODS: Retrospective, single-institution study of children (≤18 years) undergoing staged total proctocolectomy with IPAA from 2014 to 2020. Traditional two-stage and three-stage approaches including DI after IPAA were compared to two-stage approach without DI. RESULTS: 32 patients were included; of these, 7 (22%), 14 (44%), and 11 (34%) patients underwent traditional two-stage, modified two-stage, or three-stage IPAA, respectively. Following IPAA, modified two-stage patients had shorter operative time, decreased opioid utilization, quicker return to regular diet, and shorter stoma duration. After IPAA, there was similar postoperative length of stay, complication rates, readmissions, visits to the emergency department, or unplanned return to the operating room (OR) within 30 days. Anastomotic leak occurred in 2 patients; both were managed nonoperatively without evidence of pouch dysfunction. CONCLUSION: Modified two-stage IPAA with omission of DI after the IPAA stage is safe to perform in pediatric UC patients. Prospective studies with larger sample sizes are needed to identify risk factors associated with operative complications.


Subject(s)
Colitis, Ulcerative/surgery , Proctocolectomy, Restorative/methods , Adolescent , Child , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Ileostomy/statistics & numerical data , Length of Stay , Male , Operative Time , Patient Readmission/statistics & numerical data , Postoperative Complications/epidemiology , Proctocolectomy, Restorative/adverse effects , Proctocolectomy, Restorative/statistics & numerical data , Reoperation/statistics & numerical data , Retrospective Studies
7.
Am Surg ; 88(6): 1146-1152, 2022 Jun.
Article in English | MEDLINE | ID: mdl-33530718

ABSTRACT

BACKGROUND: The efficacy of clinical decision support (CDS) tools to promote antibiotic stewardship in pediatric appendicitis remains poorly understood. Here, we developed an electronic order panel (OP) to assist with decreased utilization of extended spectrum antibiotics. METHODS: Retrospective review of patients (≤18 years) at a single institution from May 2018 to October 2019 treated with ≥1 dose of preferred (narrow) or nonpreferred (broad-spectrum) antibiotics was performed, and they were categorized as pre- (PIC) or postimplementation cohorts (PISC). RESULTS: Of 234 encounters, 170 (73%) and 107 (46%) received preferred and nonpreferred antibiotics, respectively. Postimplementation cohort encounters had a sustained 50% increase in preferred antibiotic use compared to PIC (92% vs 42%, P = .014). Order panel utilization accounted for 31% of overall encounters and 44% of PISC encounters. CONCLUSION: Despite sustained improvement in antibiotic stewardship, OP utilization remains low. The use of CDS tools may not be a good process measure for quality improvement.


Subject(s)
Antimicrobial Stewardship , Appendicitis , Decision Support Systems, Clinical , Anti-Bacterial Agents/therapeutic use , Appendicitis/drug therapy , Appendicitis/surgery , Child , Electronics , Humans , Retrospective Studies
8.
J Pediatr Surg ; 57(3): 369-374, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34625277

ABSTRACT

INTRODUCTION: Timing of inguinal hernia repair (IHR) in premature infants is variable and influenced by surgeon preference and complication profile. The purpose of this study was to evaluate factors related to early IHR, defined as hernia repair during initial neonatal admission, in premature infants. METHODS: Neonatal hospitalizations of premature infants (gestational age at birth < 37 weeks and ≤ 28 days old at admission), with a diagnosis of inguinal hernia from 2010 to 2017 in HCUP National Inpatient Sample and Kid's Inpatient Sample databases were evaluated. Multivariable Cox proportional hazard models was used to estimate associations between demographics, additional procedures, hospital characteristics, and early IHR. RESULTS: Overall, 30,298 neonatal hospitalizations of premature infants with inguinal hernia were identified; 13,228 (43.3%) underwent early IHR. Early IHR was more likely with older gestational age at birth (35-36 weeks vs < 24 weeks, HR 6.05, 95% CI 4.17, 8.79), female sex (HR 1.20, 95% CI 1.07, 1.34), and undergoing concomitant gastrostomy (HR 2.51, 95% CI 1.72, 3.66). Non-Hispanic Black infants (HR 0.84, 95% CI 0.75, 0.95), infants at urban non-teaching hospitals (HR 0.15, 95% CI 0.07, 0.33), and infants at rural hospitals (HR 0.81, 95% CI 0.70, 0.97) were less likely to undergo early IHR. CONCLUSIONS: Using a nationally representative database, early IHR in premature neonates was more commonly performed in non-Hispanic White, female neonates and at urban teaching hospitals. Patient race and hospital type were determinants of early IHR in premature neonates. There is a need to further evaluate the impact of race and socioeconomic factors on outcomes of common pediatric operations like inguinal hernia repairs. LEVEL OF EVIDENCE: Level III.


Subject(s)
Hernia, Inguinal , Infant, Premature, Diseases , Child , Female , Hernia, Inguinal/epidemiology , Hernia, Inguinal/surgery , Herniorrhaphy , Hospitalization , Humans , Infant , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/surgery , Retrospective Studies
9.
Burns ; 48(3): 602-607, 2022 05.
Article in English | MEDLINE | ID: mdl-34284937

ABSTRACT

PURPOSE: Burn outcome data in infants is lacking from sub-Saharan Africa. We, therefore, sought to assess the characteristics and predictors of in-hospital burn mortality in a resource-limited setting. METHODS: We performed a retrospective study of the prospectively collected Burn Injury Surveillance database from June 2011 to December 2019. We performed bivariate analysis and Poisson regression to assess risk factors for mortality in our infant burn population. RESULTS: 115 (7.3%) infants met inclusion criteria. The median age of 8 months (IQR: 6-10) and primarily male (n = 67, 58.8%). Most burns were from scald (n = 62, 53.9%). Infant burn mortality was 12.2%. Poisson multivariable regression to determine burn mortality risk in infants showed that increased %TBSA burns (RR 1.04, 95% CI 1.01-1.07) and flame burns (RR 3.08, 95%CI 1.16-8.16) had a higher risk of mortality. Having surgery reduced the relative risk of death for infants with burns. CONCLUSION: We show that factors that increase infant burn mortality risk include percent total body surface area burn, flame burn mechanism, and lack of operative intervention. Increasing burn operative capability, particularly for infants and other children, is imperative.


Subject(s)
Burn Units , Burns , Body Surface Area , Burns/epidemiology , Child , Hospital Mortality , Humans , Infant , Male , Retrospective Studies
10.
Ann Surg ; 276(6): e976-e981, 2022 12 01.
Article in English | MEDLINE | ID: mdl-34183507

ABSTRACT

OBJECTIVE: The aim of this study was to define the training background of the actual surgical workforce providing care to pediatric patients in North Carolina (NC). BACKGROUND: Due to database limitations, pediatric surgical workforce studies have not included general surgeons (GS) who operate on children. Defining the role of GS in care delivery affects policy for clinical care and general and pediatric surgical training. METHODS: We performed a retrospective review of the NC Hospital Discharge Database (2011-2017), including pediatric patients (<18 years) undergoing the most frequent general surgery procedures. Descriptive and correlational analysis over surgical provider [Pediatric Surgeon (PS), GS], and other specialties (OSS), was performed using logistic regression modeling to identify factors associated with surgery by a PS. RESULTS: Of the 57,265 discharges analyzed, pediatric, general, and other specialty surgeons operated on 25,514 (44.6%), 18,581 (32.5%), and 9049 (15.8%), respectively. In a logistic regression model, PS had lower odds of operating on older patients [odds ratio (OR) 0.9, 95% confidence interval (CI) 0.90-0.91]. However, PS were more likely to operate on female patients (OR 1.58, 95% CI 1.53-1.65), Black (OR 1.49, 95% CI 1.43-1.56), and other minority patients (OR 1.23, 95% CI 1.17-1.29) when compared to white patients. PS were also more likely to operate on patients with private insurance (OR 1.38, 95% CI 1.33-1.43) compared to government insurance, and patients undergoing emergency surgery (OR 1.44, 95% CI 1.38-1.50). CONCLUSION: In NC, general surgeons performed a third of the operations on children. After controlling for covariates, pediatric surgeons in NC are more likely to operate on minority and emergency surgery patients, and this is the first study to describe this important practice pattern.


Subject(s)
General Surgery , Medicine , Surgeons , Humans , Female , Child , North Carolina , Retrospective Studies
12.
Am J Surg ; 221(4): 718-724, 2021 04.
Article in English | MEDLINE | ID: mdl-33678398

ABSTRACT

INTRODUCTION: Colon cancer in children and young adults is rare. We sought to compare outcomes and survival between patients ≤and>25 years of age with colon cancer. METHODS: Using the National Cancer Database, patients with colon cancer between 2004 and 2016 were identified. We included patients with histological codes consistent with invasive colon adenocarcinoma and excluded those missing data about treatment. Post-surgical outcomes and survival were compared. RESULTS: Of 531,462 patients meeting criteria, 947 were ≤25 years. Patients ≤25 had more advanced disease (stage III:44.4%vs33.4%, stage IV:27.5%vs.15.3%) and higher rates of total colectomy (8.9%vs.2.7%) and proctocolectomy (5.0%vs.0.0%) than those >25 years. Stage for stage, 5-year survival was higher in patients ≤25 than those >25years. On multivariate regression, age was not associated with increased risk of mortality while male sex and uninsured status were. CONCLUSIONS: Despite presenting with more advanced disease, patients ≤25 years with colon cancer had better survival than those >25 years.


Subject(s)
Colonic Neoplasms/mortality , Colonic Neoplasms/surgery , Adolescent , Adult , Aged , Child , Colonic Neoplasms/pathology , Female , Humans , Male , Middle Aged , Neoplasm Staging , Risk Factors , Survival Rate
14.
Int J Radiat Oncol Biol Phys ; 110(3): 821-830, 2021 07 01.
Article in English | MEDLINE | ID: mdl-33548339

ABSTRACT

PURPOSE: The ARST0332 trial for pediatric and young adults with nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) used risk-based treatment including primary resection with lower-than-standard radiation doses to optimize local control (LC) while minimizing long-term toxicity in those requiring radiation therapy (RT). RT for high-grade NRSTS was based on extent of resection (R0: negative margins, R1: microscopic margins, R2/U: gross disease/unresectable); those with >5 cm tumors received chemotherapy (CT; ifosfamide/doxorubicin). This analysis evaluates LC for patients assigned to RT and prognostic factors associated with local recurrence (LR). METHODS AND MATERIALS: Patients aged <30 years with high-grade NRSTS received RT (55.8 Gy) for R1 ≤5 cm tumor (arm B); RT (55.8 Gy)/CT for R0/R1 >5 cm tumor (arm C); or neoadjuvant RT (45 Gy)/CT plus delayed surgery, CT, and postoperative boost to 10.8 Gy R0 <5 mm margins/R1 or 19.8 Gy for R2/unresected tumors (arm D). RESULTS: One hundred ninety-three eligible patients had 24 LRs (arm B 1/15 [6.7%], arm C 7/65 [10.8%], arm D 16/113 [14.2%]) at median time to LR of 1.1 years (range, 0.11-5.27). Of 95 eligible for delayed surgery after neoadjuvant therapy, 89 (93.7%) achieved R0/R1 margins. Overall LC after RT were as follows: R0, 106 of 109 (97%); R1, 51 of 60 (85%); and R2/unresectable, 2 of 6 (33%). LR predictors include extent of delayed resection (P <.001), imaging response before delayed surgery (P < .001), histologic subtype (P <.001), and no RT (P = .046). The 5-year event-free survival was significantly lower (P = .0003) for patients unable to undergo R0/R1 resection. CONCLUSIONS: Risk-based treatment for young patients with high-grade NRSTS treated on ARST0332 produced very high LC, particularly after R0 resection (97%), despite lower-than-standard RT doses. Neoadjuvant CT/RT enabled delayed R0/R1 resection in most patients and is preferred over adjuvant therapy due to the lower RT dose delivered.


Subject(s)
Research Design , Soft Tissue Neoplasms/pathology , Soft Tissue Neoplasms/radiotherapy , Adolescent , Child , Child, Preschool , Female , Humans , Male , Neoplasm Grading , Young Adult
15.
Pediatr Surg Int ; 37(5): 649-657, 2021 May.
Article in English | MEDLINE | ID: mdl-33459861

ABSTRACT

INTRODUCTION: Intentional injuries pose a significant, yet underreported threat to children in sub-Saharan Africa. We sought to evaluate intentional injuries trends and compare outcomes between unintentional and intentional injuries in pediatric patients presenting to a tertiary care facility in Malawi. METHODS: We performed a review of pediatric (≤15 years old) trauma patients presenting to Kamuzu Central Hospital, Lilongwe, Malawi, from 2009 to 2018. Patient characteristics and outcomes were compared based on the injury intent, using bivariate and multivariate regression analysis. RESULTS: We included 42,600 pediatric trauma patients in the study. Intentional injuries accounted for 5.9% of all injuries. Children with intentional injuries were older (median, 10 vs. 6 years, p < 0.001), more likely to be male (68.4% vs. 63.9%, p < 0.001), and had significantly lower mortality (0.8% vs. 1.4%, p = 0.02) than those with unintentional injuries There was no significant change in the incidence of or mortality associated with intentional injuries. On multivariable regression, increasing age, head and cervical spine injury, night-time presentation, penetrating injury, and alcohol use were associated with increased risk of intentional harm. CONCLUSION: Intentional injury remains a significant cause of pediatric trauma in Malawi without decreasing hospital presentation incidence or mortality. In sub-Saharan Africa, there is a need to develop comprehensive plans and policies to protect children. LEVEL OF EVIDENCE: II.


Subject(s)
Child Abuse/statistics & numerical data , Adolescent , Child , Child, Preschool , Female , Humans , Incidence , Infant , Malawi , Male , Pediatrics , Retrospective Studies , Wounds and Injuries
16.
Infect Drug Resist ; 14: 1-10, 2021.
Article in English | MEDLINE | ID: mdl-33442271

ABSTRACT

PURPOSE: The biology of chronic wounds is complex and many factors act concurrently to impede healing progress. In this study, the dynamics of microflora changes and their antibiotic susceptibility patterns were evaluated longitudinally over 30 days using data from 28 patients with a total of 47 chronic lower extremity wounds. MATERIALS AND METHODS: In this study, colonized wound isolates were characterized using cultural, biochemical, and VITEK 2 methods. Antibiotic susceptibility patterns of the wound isolates were analyzed using various phenotypic assays. Furthermore, antimicrobial resistance patterns and the presence of mutations were evaluated by a genotypic assay, whole-genome sequencing (WGS). RESULTS: Staphylococcus aureus and Pseudomonas aeruginosa were found to be the most common strains at early time points, while members of Enterobacteriaceae were prevalent at later stages of infection. Antimicrobial resistance testing and whole-genome sequencing revealed that the molecular and phenotypic characteristics of the identified wound pathogens remained relatively stable throughout the study period. It was also noted that Enterobacter and Klebsiella species may serve as reservoirs for quinolone resistance in the Pacific region. CONCLUSION: Our observations showed that wounds were colonized with diverse bacteria and interestingly their numbers and/or types were changed over the course of infection. The rapid genetic changes that accompanied the first 4 weeks after presentation did not directly contribute to the development of antibiotic resistance. In addition, standard wound care procedures did not appear to select for resistant bacterial strains. Future efforts should focus on defining those genetic changes associated with the wound colonizing microorganisms that occur beyond 4 weeks.

17.
Cancer Med ; 10(3): 857-866, 2021 02.
Article in English | MEDLINE | ID: mdl-33340280

ABSTRACT

BACKGROUND: Strategies to optimize management in rhabdomyosarcoma (RMS) include risk stratification to assign therapy aiming to minimize treatment morbidity yet improve outcomes. This analysis evaluated the relationship between complete metabolic response (CMR) as assessed by 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET) imaging and event-free survival (EFS) in intermediate-risk (IR) and high-risk (HR) RMS patients. METHODS: FDG-PET imaging characteristics, including assessment of CMR and maximum standard uptake values (SUVmax) of the primary tumor, were evaluated by central review. Institutional reports of SUVmax were used when SUVmax values could not be determined by central review. One hundred and thirty IR and 105 HR patients had FDG-PET scans submitted for central review or had SUVmax data available from institutional report at any time point. A Cox proportional hazards regression model was used to evaluate the relationship between these parameters and EFS. RESULTS: SUVmax at study entry did not correlate with EFS for IR (p = 0.32) or HR (p = 0.86) patients. Compared to patients who did not achieve a CMR, EFS was not superior for IR patients who achieved a CMR at weeks 4 (p = 0.66) or 15 (p = 0.46), nor for HR patients who achieved CMR at week 6 (p = 0.75) or 19 (p = 0.28). Change in SUVmax at week 4 (p = 0.21) or 15 (p = 0.91) for IR patients or at week 6 (p = 0.75) or 19 (p = 0.61) for HR patients did not correlate with EFS. CONCLUSION: Based on these data, FDG-PET does not appear to predict EFS in IR or HR-RMS. It remains to be determined whether FDG-PET has a role in predicting survival outcomes in other RMS subpopulations.


Subject(s)
Biomarkers, Tumor/metabolism , Fluorodeoxyglucose F18/metabolism , Positron Emission Tomography Computed Tomography/methods , Rhabdomyosarcoma/metabolism , Rhabdomyosarcoma/mortality , Child , Child, Preschool , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Prognosis , Radiopharmaceuticals/metabolism , Rhabdomyosarcoma/pathology , Rhabdomyosarcoma/therapy , Survival Rate
18.
J Pediatr Hematol Oncol ; 43(5): e685-e688, 2021 07 01.
Article in English | MEDLINE | ID: mdl-32769559

ABSTRACT

BACKGROUND: Sclerosing encapsulating peritonitis (SEP) is a rare chronic inflammatory condition characterized by small bowel encapsulation by a thick fibrocollagenous membrane. Patients with SEP often present with nonspecific symptoms, such as abdominal pain and distension, however some patients may present with symptoms suggestive of intestinal obstruction. Secondary SEP has been reported in patients undergoing peritoneal dialysis and has been recently described in adults following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). OBSERVATIONS: We report a clinical case of a 13-year-old female who presented with worsening abdominal pain and distension and persistent emesis who was found to have SEP 13 months following CRS and HIPEC for management of desmoplastic small round cell tumor and subsequently required operative intervention. CONCLUSION: Although there have been published reports of adult patients experiencing cases of SEP following CRS/HIPEC, this is the first published case of secondary SEP occurring in a pediatric oncology patient.


Subject(s)
Cytoreduction Surgical Procedures , Desmoplastic Small Round Cell Tumor/therapy , Hyperthermic Intraperitoneal Chemotherapy , Peritoneal Neoplasms/therapy , Peritonitis/etiology , Adolescent , Cytoreduction Surgical Procedures/adverse effects , Desmoplastic Small Round Cell Tumor/pathology , Female , Humans , Hyperthermic Intraperitoneal Chemotherapy/adverse effects , Peritoneal Neoplasms/pathology , Peritonitis/pathology
19.
J Pediatr Surg ; 56(4): 648, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33223224

ABSTRACT

This Commentary by the APSA Board of Governors enthusiastically endorses the position paper "Diversity, Equity, and Inclusion: A Strategic Priority for the American Pediatric Surgical Association".


Subject(s)
Societies, Medical , Child , Humans , United States
20.
J Pediatr Surg ; 56(1): 115-120, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33131774

ABSTRACT

INTRODUCTION: Enhanced recovery after surgery (ERAS) pathways in adult colorectal surgery are known to reduce complications, readmissions, and length of stay (LOS). However, there is a paucity of ERAS data for pediatric colorectal surgery. METHODS: A 2014-2018 single-institution, retrospective cohort study was performed on pediatric colorectal surgery patients (2-18 years) pre- and post-ERAS pathway implementation. Bivariate analysis and linear regression were used to determine if ERAS pathway implementation reduced total morphine milligram equivalents per kilogram (MME/kg), LOS, and time to oral intake. RESULTS: 98 (70.5%) and 41 (29.5%) patients were managed with ERAS and non-ERAS pathways, respectively. There was no statistical difference in age, sex, diagnosis, or use of laparoscopic technique between cohorts. The ERAS cohort experienced a significant reduction in total MME/kg, Foley duration, time to oral intake, and LOS with no increase in complications. The presence of an ERAS pathway reduced the total MME/kg (-0.071, 95% CI -0.10, -0.043) when controlling for covariates. CONCLUSION: The use of an ERAS pathway reduces opioid utilization, which is associated with a reduction in LOS and expedites the initiation of oral intake, in colorectal pediatric surgery patients. Pediatric ERAS pathways should be incorporated into the care of pediatric patients undergoing colorectal surgery. LEVEL OF EVIDENCE: Level III evidence. TYPE OF STUDY: Retrospective cohort study.


Subject(s)
Colorectal Surgery , Digestive System Surgical Procedures , Enhanced Recovery After Surgery , Adult , Child , Humans , Length of Stay , Postoperative Complications/epidemiology , Retrospective Studies
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