Publications by authors named "Hewitt G"

Objective: Patients with anorectal malformations (ARMs) may have concurrent gynecologic abnormalities. As patients grow, they typically transition from pediatric subspeciality care and seek adult obstetrics and gynecology (OB/GYN)-related services. We aimed to assess adult OB/GYN physicians' knowledge, competency, and comfort regarding meeting the sexual and reproductive health care needs of patients with ARMs.

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  • There is currently no standardized grading system for pediatric female genital trauma (PFGT), leading to potential overuse of medical resources based on injury severity. A high-volume trauma center aimed to address this by analyzing treatment patterns and outcomes and developing a new grading system to improve management decisions.
  • A study of 353 female patients under 19 years old with genital trauma revealed that lower-grade injuries (grades 1 and 2) rarely needed surgical repair and primarily utilized local sedation, while higher-grade injuries (grades 5 and 6) typically required more intensive surgical intervention and general anesthesia.
  • The proposed management algorithm recommends minimal surgical intervention for lower-grade injuries and encourages surgical consultation for higher-grade
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Study Objective: Mullerian duct anomalies are common in females with anorectal malformations (ARMs), although there are no universally recommended screening protocols for identification. Historically, at our institution, we have recommended a screening pelvic ultrasound (PUS) 6 months after thelarche and menarche. We aimed to evaluate outcomes associated with our post-thelarche screening PUS in females with ARMs.

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Study Objectives: Recommendations from the Children's Oncology Group Long-Term Follow-Up (COG-LTFU) Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer emphasize the importance of reproductive health care, yet little is known regarding adherence to these recommendations and non-fertility-related sexual and reproductive health (SRH) outcomes.

Methods: Follow-up of outcomes on the basis of the COG-LTFU guidelines was assessed in female patients who underwent fertility preservation consultation before gonadotoxic therapy between 2016 and 2022 at a single institution and were at least 6 months from treatment completion.

Results: We included 140 patients, with a mean time of 2.

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Repair of DNA damage is essential for the maintenance of genome stability and cell viability. DNA double strand breaks (DSBs) constitute a toxic class of DNA lesion and multiple cellular pathways exist to mediate their repair. Robust and titratable assays of cellular DSB repair (DSBR) are important to functionally interrogate the integrity and efficiency of these mechanisms in disease models as well as in response to genetic or pharmacological perturbations.

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  • The study aimed to evaluate the effectiveness of MRI in predicting ovarian cancer in young patients compared to other diagnostic tools like ultrasounds and tumor markers.
  • Out of 1,053 patients, 10% were found to have malignancies, revealing MRI's sensitivity and specificity to be 60% and 94% respectively, while ultrasound was less sensitive but more specific.
  • The results suggest that MRI shows better sensitivity in ambiguous cases compared to ultrasound, and both MRI and tumor markers tend to agree, indicating that a combined approach could optimize preoperative assessment.
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Reactive aldehydes are abundant endogenous metabolites that challenge homeostasis by crosslinking cellular macromolecules. Aldehyde-induced DNA damage requires repair to prevent cancer and premature aging, but it is unknown whether cells also possess mechanisms that resolve aldehyde-induced RNA lesions. Here, we establish photoactivatable ribonucleoside-enhanced crosslinking (PAR-CL) as a model system to study RNA crosslinking damage in the absence of confounding DNA damage in human cells.

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Importance: Although most ovarian masses in children and adolescents are benign, many are managed with oophorectomy, which may be unnecessary and can have lifelong negative effects on health.

Objective: To evaluate the ability of a consensus-based preoperative risk stratification algorithm to discriminate between benign and malignant ovarian pathology and decrease unnecessary oophorectomies.

Design, Setting, And Participants: Pre/post interventional study of a risk stratification algorithm in patients aged 6 to 21 years undergoing surgery for an ovarian mass in an inpatient setting in 11 children's hospitals in the United States between August 2018 and January 2021, with 1-year follow-up.

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Study Objective: To improve our understanding of reproductive health and sexual function in women with cloacal malformations and other anorectal malformations (ARMs) METHODS: An observational cross-sectional survey was administered to individuals assigned female at birth aged 12 to 55 with ARMs and cloacal malformations cared for at our institution. Data included age of thelarche/menarche and questions on body image, gynecologic anatomy, sexual function, and pregnancy.

Results: Twenty-one patients responded in the ARM group and 30 in the cloacal malformation group.

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Study Objective: To examine the recurrence rates of pediatric benign ovarian neoplasms METHODS: A retrospective review of females up to 21 years of age who underwent surgery for a benign ovarian neoplasm at 8 pediatric hospitals from January 2010 through December 2016 was conducted. Data include primary operation details, follow-up imaging, and reoperation details.

Results: Four hundred and twenty-six females were included in our cohort, with a median age of 15 years at the time of the primary operation.

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  • POLQ is an important protein for repairing DNA double-strand breaks (DSBs) through a process called microhomology-mediated end-joining (MMEJ) and is found at higher levels in various cancers.
  • Inhibiting POLQ leads to synthetic lethality in cancer cells that lack certain repair mechanisms (like HR and Shieldin), suggesting a strong reliance on MMEJ for repair.
  • The study reveals that when POLQ is absent, cells accumulate gaps in their DNA, and POLQ works in a way that could drive genetic changes in cancer, highlighting its role in both gap sealing and overall cell survival.
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Background: Online communication has become an integral aspect of daily life for young people internationally. Very little research has examined whether the association between social media use and well-being depends on who young people engage with (i.e.

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Study Objective: Describe the current practice patterns and diagnostic accuracy of frozen section (FS) pathology for children and adolescents with ovarian masses DESIGN: Prospective cohort study from 2018 to 2021 SETTING: Eleven children's hospitals PARTICIPANTS: Females age 6-21 years undergoing surgical management of an ovarian mass INTERVENTIONS: Obtaining intraoperative FS pathology MAIN OUTCOME MEASURE: Diagnostic accuracy of FS pathology RESULTS: Of 691 patients who underwent surgical management of an ovarian mass, FS was performed in 27 (3.9%), of which 9 (33.3%) had a final malignant pathology.

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Study Objective: To evaluate failure of initial operative therapy (incomplete tumor removal) of ovarian-sparing surgery for pediatric benign ovarian neoplasms.

Methods: A retrospective review of patients up to 21 years of age who underwent ovarian-sparing surgery for a benign ovarian neoplasm from 2010 to 2016 at 8 pediatric hospitals was conducted. Failure of initial operative therapy is defined as a radiologically suspected or pathologically confirmed ipsilateral lesion with the same pathology as the primary neoplasm within 12 weeks of the initial operation.

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Background: VACTERL association is defined by the presence of 3 or more anomalies in any of the following systems: vertebral, anorectal, cardiac, trachea-esophageal, renal, or limb. This study hypothesized that the presence of VACTERL association would correlate with an increased risk of gynecologic anomalies in patients with anorectal malformation (ARM).

Methods: This study is a cross-sectional, retrospective analysis from the prospectively collected, multicenter registry of the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC).

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Study Objective: The purpose of this case series is to describe the change in capability to perform self-selected activities in adolescent and young adult patients with chronic pelvic pain and surgically proven endometriosis following pelvic floor physical therapy as part of multidisciplinary treatment.

Design: Retrospective case series SETTING: Tertiary care pediatric hospital PARTICIPANTS: Twenty patients with ages ranging from 14 to 22 years and a median age of 16.5 years with biopsy-confirmed endometriosis INTERVENTION: Pelvic floor physical therapy MAIN OUTCOME MEASURE(S): Patient-Specific Functional Scale (PSFS) outcome measure RESULTS: Patients had a clinically significant functional improvement (median score of 6.

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  • The 53BP1-RIF1-shieldin pathway is crucial for maintaining genome stability by preventing the degradation of DNA ends at double-strand breaks (DSBs).
  • RIF1 is recruited to DSBs through interaction with phospho-53BP1 and is influenced by the methylation of histone H3 at lysine 4, mediated by SETD1A-BOD1L.
  • Impairing SETD1A or BOD1L disrupts RIF1's ability to localize to DSBs, leading to issues in DNA repair and potential therapeutic resistance in certain cancer cells, highlighting the pathway's clinical significance.
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Background: The objective of this study was to determine the rates at which gynecologic history and related exams are performed among adolescent females presenting with abdominal pain and whether the rates differ between patients seeking care at a pediatric compared with a general emergency department (ED).

Methods: We conducted a retrospective cohort study of female patients aged 12-21 years who presented to the ED for a chief complaint of abdominal pain at either a single academic children's ED or a single general academic ED during 2016. We examined differences in the rates of gynecologic history and related exams between institutions, before and after adjustment with inverse probability weights.

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Background: With increased surgeon comfort using laparoscopy, we hypothesized resection of pediatric ovarian dermoids using laparoscopy would yield a shorter length of stay and no increase in morbidity or recurrence compared to laparotomy.

Methods: A retrospective review was performed amongst eleven pediatric hospitals. Patients aged 2 to 21 who underwent resection of an ovarian dermoid from 2010 to 2020 were included.

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Study Objective: To assess the preoperative imaging impression and surgeon diagnostic accuracy for pediatric ovarian mature cystic teratomas (MCTs) DESIGN: Retrospective review SETTING: Eleven pediatric hospitals PARTICIPANTS: Patients ages 2 to 21 who underwent surgical management of an ovarian neoplasm or adnexal torsion with an associated ovarian lesion INTERVENTION: None MAIN OUTCOME MEASURES: Preoperative imaging impression, surgeon diagnosis, tumor markers, and pathology RESULTS: Our cohort included 946 females. Final pathology identified 422 (45%) MCTs, 405 (43%) other benign pathologies, and 119 (12%) malignancies. Preoperative imaging impression for MCTs had a 70% sensitivity, 92% specificity, 88% positive predictive value (PPV), and 79% negative predictive value (NPV).

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Homologous recombination-deficient (HRD) tumours, including those harbouring mutations in the BRCA genes, are hypersensitive to treatment with inhibitors of poly(ADP-ribose) polymerase (PARPis). Despite high response rates, most HRD cancers ultimately develop resistance to PARPi treatment through reversion mutations or genetic/epigenetic alterations to DNA repair pathways. Counteracting these resistance pathways, thereby increasing the potency of PARPi therapy, represents a potential strategy to improve the treatment of HRD cancers.

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The chromatin remodeler ALC1 is recruited to and activated by DNA damage-induced poly(ADP-ribose) (PAR) chains deposited by PARP1/PARP2/HPF1 upon detection of DNA lesions. ALC1 has emerged as a candidate drug target for cancer therapy as its loss confers synthetic lethality in homologous recombination-deficient cells. However, structure-based drug design and molecular analysis of ALC1 have been hindered by the requirement for PARylation and the highly heterogeneous nature of this post-translational modification.

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Cloacal malformations are among the most complex types of anorectal malformation and are characterized by the urological, genital, and intestinal tracts opening through a single common channel in the perineum. Long-term outcome is affected by multiple factors, which include anatomical variants of the malformation itself, associated anomalies, and the surgical approach. Reconsidering these variables and their influence on "patient important" function might lead to strategies that are more outcome-driven than focused on the creation of normal anatomy.

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Background: Fetus-in-fetu (FIF) is a rare, congenital soft tissue mass typically occurring retroperitoneally in neonates younger than 18 months. We present a 13-year-old girl with an ovarian FIF occurrence and subsequent residual regrowth after resection.

Case: A 13-year-old girl presented with abdominal pain and was found to have a 19-cm, complex, right adnexal mass.

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Purpose: Research demonstrates a strong socioeconomic gradient in health and well-being. However, many studies rely on unidimensional measures of socioeconomic status (SES) (e.g.

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