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BACKGROUND: Oral mucositis (OM) is a painful and common complication of hematopoietic stem cell transplant (HSCT). The Children's Oncology Group recently published guidelines recommending photobiomodulation (PBM) for preventing and treating OM in pediatric HSCT patients. However, this is a rarely used intervention in pediatric hospitals. PROCEDURE: Patients undergoing allogeneic HSCT, or autologous HSCT for a neuroblastoma diagnosis, had PBM administered from the first day of conditioning to transplant Day +20. We successfully developed a standardized treatment protocol and workflow to ensure consistent and uniform delivery of PBM. In addition, clinical patient data were compared before and after PBM implementation. RESULTS: The administration of PBM at our center was feasible, but required dedicated staff. A registered nurse (RN) was determined to be the best fit to deliver PBM. Sixty-two patients received PBM from October 2022 to September 2023; patients from 2021 before PBM implementation were used for comparison. Patients receiving PBM were more likely (p = .03) to engage in teeth brushing (56/62 = 90%) compared to baseline (61/81 = 75%). Mean days of OM decreased from 11.3 to 9 days; patients who received PBM were less likely (p < .001) to be discharged on total parental nutrition (TPN) (11/62 = 18%) compared to baseline (50/82 = 61%). OM-related supportive care costs (TPN and patient-controlled anesthesia [PCA]) were lower (p = .02) for those who received PBM (median cost = $31,229.87 vs. $37,370.66). CONCLUSION: PBM, as the standard of care in the pediatric HSCT population, is safe, feasible, and well-tolerated. At our center, a dedicated RN was critical to providing standardized treatment and ensuring sustainability.
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Trasplante de Células Madre Hematopoyéticas , Terapia por Luz de Baja Intensidad , Estomatitis , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Estomatitis/etiología , Estomatitis/prevención & control , Estomatitis/terapia , Niño , Masculino , Femenino , Terapia por Luz de Baja Intensidad/métodos , Preescolar , Adolescente , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Lactante , Estudios de Seguimiento , PronósticoRESUMEN
PURPOSE: To compare the clinical and patient-reported outcomes of adolescent patients who underwent anterior cruciate ligament reconstruction (ACLR) with quadriceps tendon (QT) versus hamstring tendon (HT) autograft. METHODS: This was a retrospective cohort study of adolescent patients aged 18 years or younger treated at a single tertiary care children's hospital who underwent primary transphyseal ACLR using QT or HT between January 2018 and December 2019. All patients had minimum 6-month follow-up. Outcomes included isokinetic strength testing, postoperative Patient-Reported Outcomes Measurement Information System and International Knee Documentation Committee scores, and complications; these were compared between the QT and HT cohorts. RESULTS: A total of 84 patients (44 HT and 40 QT patients) were included. The QT cohort had a higher proportion of male patients (62.5% vs 34.1%, P = .01). At 3 months, HT patients had a lower hamstring-quadriceps (H/Q) strength ratio (60.7 ± 11.0 vs 79.5 ± 18.6, P < .01) and lower Limb Symmetry Index in flexion (85.6 ± 16.1 vs 95.5 ± 15.7, P = .01) whereas QT patients had a lower Limb Symmetry Index in extension (67.3 ± 9.5 vs 77.4 ± 10.7, P < .01). The H/Q ratio at 6 months was lower in HT patients (59.4 ± 11.5 vs 66.2 ± 7.5, P < .01). Patient-Reported Outcomes Measurement Information System and International Knee Documentation Committee scores were not different at 3 months or latest follow-up. QT patients had more wound issues (20.0% vs 2.3%, P = .01). Patients receiving HT autograft had more ipsilateral knee injuries (18.2% vs 2.5%, P = .03), but there was no difference in graft failure for ACLR using HT versus QT (9.1% vs 2.5%, P = .36). CONCLUSIONS: There were no differences in patient-reported outcome measures between patients receiving QT autografts and those receiving HT autografts. Patients with QT grafts had more postoperative wound issues but a lower rate of ipsilateral knee complications (graft failure or meniscal tear). Differences in quadriceps and hamstring strength postoperatively compared with the contralateral limb were observed for adolescent ACLR patients receiving QT and HT autografts, respectively. This contributed to higher H/Q ratios seen at 3 and 6 months postoperatively for patients receiving QT autografts. LEVEL OF EVIDENCE: Level III, retrospective comparative therapeutic study.
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BACKGROUND: Achilles tendon injuries are common in adults, and there is extensive literature describing the injury characteristics and treatment of these adult injuries. However, Achilles injuries are rare in the pediatric population and as a result, there is limited research reported on this age group. We therefore sought to characterize the injury presentation, treatment and outcomes for pediatric patients with partial and complete Achilles injuries. METHODS: A retrospective chart review was conducted of patients aged 0-18 treated for Achilles tendon injuries at 2 geographically distinct tertiary institutions between 2008 and 2021. Data collected included demographics, injury characteristics, and treatment course. Injury types were separated into 2 cohorts: traumatic Achilles injuries and ruptures due to muscular contraction. Traumatic injuries were further delineated into 2 injury mechanisms: open injuries related to penetrating trauma and closed injuries related to blunt trauma. Standard descriptive analyses were utilized to summarize findings. RESULTS: Thirty-nine patients (43.6% female, median age 15 years) were identified, 29 (74.4%) of whom had complete tears. Twenty-five patients (64.1%) presented with traumatic injuries; among these, 48.0% (n=12/25) were ≤12 years. All patients ≤12 years sustained a traumatic injury. The most common traumatic mechanism was an open laceration due to penetrating trauma (68.0%), followed by closed ruptures associated with blunt trauma (32.0%). Fourteen patients (35.9%) presented with closed ruptures due to muscular contraction. Four patients (10.2%) had a prior history of clubfoot treated with Achilles tenotomy. Thirty-five patients (89.7%) were surgically treated with an open repair. The median immobilization period across all patients was 11 weeks (interquartile range: 10-12), starting most commonly with a posterior splint (46.2%) and concluding with a CAM boot (94.9%). Of patients with full follow-up data (n=22/39), all resumed normal activities, with a median clearance time of 6 months (interquartile range: 5-7.9). CONCLUSIONS: We found that older adolescents (≥14 y) were more likely to rupture their Achilles tendon through a forceful muscular contraction, whereas younger patients (≤12 y) were more likely to injure their Achilles via a traumatic mechanism. Most patients were treated operatively and returned to sports at a median time of 6 months. A further prospective study is warranted to better characterize treatment protocols and patient outcomes in this population. LEVEL OF EVIDENCE: Level-IV.
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Tendón Calcáneo , Traumatismos de los Tendones , Heridas no Penetrantes , Adulto , Adolescente , Humanos , Niño , Femenino , Masculino , Tendón Calcáneo/cirugía , Estudios Retrospectivos , Estudios Prospectivos , Traumatismos de los Tendones/etiología , Traumatismos de los Tendones/cirugía , Rotura/cirugía , Resultado del TratamientoRESUMEN
Pediatric acute myeloid leukemia (AML) is a devastating disease with a high risk of relapse. Current risk classification designates patients as high or low risk (LR) based on molecular features and therapy response. However, 30% of LR patients still suffer relapse, indicating a need for improvement in risk stratification. Cytokine levels, such as IL-6 and IL-10, have been shown to be prognostic in adult AML but have not been well studied in children. Previously, we reported elevated IL-6 levels in pediatric AML bone marrow to be associated with inferior prognosis. Here, we expanded our investigation to assess cytokine levels in diagnostic peripheral blood plasma (PBP) of pediatric AML patients and determined correlation with outcome. Diagnostic PBP was obtained from 80 patients with LR AML enrolled on the Children's Oncology Group AAML1031 study and normal PBP from 11 controls. Cytokine levels were measured and correlation with clinical outcome was assessed. IL-6, TNFα, MIP-3a, and IL-1ß were significantly higher in AML patients versus controls when corrected by the Bonferroni method. Furthermore, elevated TNFα and IL-10 were significantly associated with inferior outcomes. Our data demonstrate that in diagnostic PBP of LR pediatric AML patients, certain cytokine levels are elevated as compared to healthy controls and that elevated TNFα and IL-10 are associated with inferior outcomes, supporting the idea that an abnormal inflammatory state may predict poor outcomes. Studies are needed to determine the mechanisms by which these cytokines impact survival, and to further evaluate their use as prognostic biomarkers in pediatric AML.
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Interleucina-10 , Leucemia Mieloide Aguda , Adulto , Humanos , Niño , Interleucina-10/uso terapéutico , Factor de Necrosis Tumoral alfa , Interleucina-6/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Pronóstico , Citocinas , RecurrenciaRESUMEN
CHG-based hygiene methods are often a component of daily hygiene bundles to prevent central line-associated blood stream infections (CLABSIs) in pediatric hematology-oncology patients; however, adherence with 2% CHG wipes was inconsistent within our institution, risking infection for immunocompromised patients. A new 4% CHG foam method offers an alternative and is applied while bathing, as opposed to wipes used 1 h after bathing. An initial cohort of 24 high-risk oncology and bone marrow transplant (BMT) patients agreed to use 4% CHG foam in place of wipes, and then answered surveys to describe their experiences. Ninety-two percent preferred foam over wipes and were more likely to use the foam moving forward. CHG foam was then made available as an option to all patients in need of central line care upon admission to the hospital. Hygiene bundles in the electronic medical record were reviewed to measure baseline adherence rates. Random audits by nursing administration prospectively assessed CHG adherence. CLABSI data were collected prospectively with routine quality metric reports. Results were analyzed using run charts and u-charts, respectively. Hematology-Oncology unit adherence rates remained at a higher rate of adherence, and BMT unit adherence rates increased from an average of 55%-81.6% (p < 0.001). Primary CLABSIs remained rare events (average <1/1000 CVL days). On cost analysis, utilizing CHG foam results in an annual savings estimate of $40,000 for a 24-bed unit. In conclusion, 4% CHG foam provides a cost-effective and patient-preferred option for daily hygiene that maintains CLABSI preventative efforts.
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Antiinfecciosos Locales , Infecciones Relacionadas con Catéteres , Infección Hospitalaria , Niño , Humanos , Trasplante de Médula Ósea , Infección Hospitalaria/prevención & control , Satisfacción del Paciente , Clorhexidina/uso terapéutico , Satisfacción Personal , Infecciones Relacionadas con Catéteres/prevención & controlRESUMEN
BACKGROUND: Bloodstream infections (BSIs) cause morbidity and mortality in pediatric patients with leukemia. Antibiotic prophylaxis during periods of chemotherapy-induced neutropenia may reduce the incidence of BSIs. PROCEDURE: A levofloxacin prophylaxis guideline was implemented for pediatric patients with acute myeloid leukemia and relapsed acute lymphoblastic leukemia. We conducted a retrospective cohort study over 4 years (2 years pre and 2 years post implementation) of the practice guideline to assess the impact on central line-associated bloodstream infections (CLABSI) and BSI events. Secondary outcomes included incidence of Clostridioides difficile-associated diarrhea, bacteremia due to multidrug-resistant organisms (MDRO), and bacteremia due to levofloxacin nonsusceptible organisms. STATA was used for data analysis. RESULTS: Sixty-three and 72 patients met inclusion criteria for the pre- and postimplementation cohorts, respectively. Demographics were similar between the groups. We observed 60 BSI events in the pre-group versus 49 events in the post-group (p = .1). Bacteremia due to Gram-negative rods (risk ratio [RR] 0.37 [0.21, 0.66], p < .001) and National Healthcare Safety Network (NHSN) CLABSIs (RR 0.62 [0.44, 0.89], p = .01) were significantly reduced in the postimplementation group. The incidences of C. difficile-associated diarrhea and MDRO bacteremia were similar between groups. However, we observed an increase in the incidence of BSI due to Gram-negative rods that were nonsusceptible to levofloxacin (RR 3.38 [0.72, 6.65], p < .001). CONCLUSION: Following implementation of a levofloxacin prophylaxis guideline, we observed a significant decrease in BSIs due to Gram-negative rods and NHSN CLABSIs. Vigilant monitoring of outcomes post guideline implementation is critical to track emergence of resistant organisms.
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Bacteriemia , Clostridioides difficile , Infección Hospitalaria , Leucemia Mieloide Aguda , Sepsis , Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Bacteriemia/epidemiología , Bacteriemia/etiología , Bacteriemia/prevención & control , Niño , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Atención a la Salud , Diarrea/inducido químicamente , Diarrea/epidemiología , Estudios de Seguimiento , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Levofloxacino/uso terapéutico , Estudios Retrospectivos , Sepsis/complicacionesRESUMEN
Current therapies for relapsed/refractory (R/R) pediatric myeloid neoplasms are inadequately effective. Real-world data (RWD) can improve care by augmenting traditional studies and include individuals not eligible for clinical trials. The Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) consortium recently completed T2016-003, a phase 1 study of decitabine, vorinostat, fludarabine, cytarabine, and granulocyte colony-stimulating factor (G-CSF) in R/R acute myeloid leukemia (AML), which added epigenetic drugs to a cytotoxic backbone. We report results of RWD from six centers that treated 28 pediatric patients (26 with AML, two with other myeloid neoplasms) identically to the TACL study but who were not enrolled. This allowed unique analyses and the ability to compare data with the 35 TACL study patients. The overall response rate (ORR) (complete response [CR] plus CR with incomplete count recovery) among 26 RWD evaluable patients was 65%. The ORR of 13 patients with relapsed AML with epigenetic alterations was 69% (T2016-003 + RWD: 68%, n = 25), of eight patients with refractory AML was 38% (T2016-003 + RWD: 41%, n = 17) and of five patients with therapy-related AML (t-AML) was 80% (T2016-003 + RWD: 75%, n = 8). The mean number of Grade 3/4 toxicities experienced by the T2016-003-eligible RWD population (n = 22) (one per patient-cycle) was not meaningfully different than those (n = 6) who would have been TACL study-ineligible secondary to comorbidities (two per patient-cycle). Overall, this therapy was well tolerated and effective in pediatric patients with R/R myeloid neoplasms, particularly those with epigenetic alterations, t-AML, and refractory disease.
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Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia Mieloide Aguda , Recurrencia Local de Neoplasia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Citarabina , Decitabina/uso terapéutico , Factor Estimulante de Colonias de Granulocitos , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Vidarabina , Vorinostat/uso terapéuticoRESUMEN
Rubinstein-Taybi syndrome (RSTS) is a rare disorder characterized by developmental delay, short stature, dysmorphic facies and skeletal abnormalities. RSTS has been linked to a variety of malignant and benign tumors, but the frequency and characteristics of RSTS-related neoplasms remain unclear. We describe a unique case of near haploid B-cell lymphoblastic leukemia (B-ALL) in a 6-year-old girl with RSTS who harbors a likely pathogenic variant in CREBBP. Somatic CREBBP variants are enriched in some subsets of ALL; however, germline variants have not been previously described in childhood leukemia and may represent an underrecognized predisposition to malignancy. Our patient's disease responded poorly to conventional chemotherapy and relapsed following a complete remission achieved with CD19 CAR T cell therapy. We propose that the constitutional CREBBP variant may have played a significant role in the leukemia's resistance to chemotherapy and this patient's poor response to therapy.
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Linfoma de Burkitt , Leucemia-Linfoma Linfoblástico de Células Precursoras , Síndrome de Rubinstein-Taybi , Proteína de Unión a CREB/genética , Niño , Aberraciones Cromosómicas , Femenino , Genotipo , Haploidia , Humanos , Mutación , Síndrome de Rubinstein-Taybi/genética , Síndrome de Rubinstein-Taybi/patologíaRESUMEN
PURPOSE OF REVIEW: Acute myeloid leukemia (AML) in children remains a challenging disease to cure with suboptimal outcomes particularly when compared to the more common lymphoid leukemias. Recent advances in the genetic characterization of AML have enhanced understanding of individualized patient risk, which has also led to the development of new therapeutic strategies. Here, we review key cytogenetic and molecular features of pediatric AML and how new therapies are being used to improve outcomes. RECENT FINDINGS: Recent studies have revealed an increasing number of mutations, including WT1, CBFA2T3-GLIS2, and KAT6A fusions, DEK-NUP214 and NUP98 fusions, and specific KMT2A rearrangements, which are associated with poor outcomes. However, outcomes are starting to improve with the addition of therapies such as gemtuzumab ozogamicin and FLT3 inhibitors, initially developed in adult AML. The combination of advanced risk stratification and ongoing improvements and innovations in treatment strategy will undoubtedly lead to better outcomes for children with AML.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Proteínas de Homeodominio/genética , Inmunoterapia/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Proteínas de Complejo Poro Nuclear/genética , Proteínas de Fusión Oncogénica/genética , Niño , HumanosRESUMEN
Recurrence and drug resistance are major challenges in the treatment of acute myeloid leukemia (AML) that spur efforts to identify new clinical targets and active agents. STAT3 has emerged as a potential target in resistant AML, but inhibiting STAT3 function has proven challenging. This paper describes synthetic studies and biological assays for a naphthalene sulfonamide inhibitor class of molecules that inhibit G-CSF-induced STAT3 phosphorylation in cellulo and induce apoptosis in AML cells. We describe two different approaches to inhibitor design: first, variation of substituents on the naphthalene sulfonamide core allows improvements in anti-STAT activity and creates a more thorough understanding of anti-STAT SAR. Second, a novel approach involving hybrid sulfonamide-rhodium(ii) conjugates tests our ability to use cooperative organic-inorganic binding for drug development, and to use SAR studies to inform metal conjugate design. Both approaches have produced compounds with improved binding potency. In vivo and in cellulo experiments further demonstrate that these approaches can also lead to improved activity in living cells, and that compound 3aa slows disease progression in a xenograft model of AML.
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Antineoplásicos/química , Leucemia Mieloide Aguda/tratamiento farmacológico , Naftalenos/química , Inhibidores de Proteínas Quinasas/química , Factor de Transcripción STAT3/antagonistas & inhibidores , Sulfonamidas/química , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ratones , Modelos Moleculares , Terapia Molecular Dirigida , Neoplasias Experimentales , Oxidación-Reducción , Unión Proteica , Inhibidores de Proteínas Quinasas/farmacología , Factor de Transcripción STAT3/genética , Relación Estructura-ActividadRESUMEN
A case of a 19-year-old female with low-risk acute myeloid leukemia is presented who was diagnosed with idiopathic hyperammonemic encephalopathy following the development of abrupt neurologic decline, respiratory alkalosis, and elevated plasma ammonia levels of unknown etiology. Delayed symptom recognition of this exceedingly rare condition contributes to the often fatal outcomes of idiopathic hyperammonemic encephalopathy. As illustrated by this case, prompt diagnosis and utilization of a variety of ammonia-modulating treatment modalities can result in remarkable clinical recovery. This case provides guidance to clinicians in counseling families about the possibility of neurologic recovery in similar clinical scenarios.
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Encefalopatías/complicaciones , Hiperamonemia/complicaciones , Leucemia Mieloide Aguda/fisiopatología , Síndromes de Neurotoxicidad/mortalidad , Fenilbutiratos/uso terapéutico , Benzoato de Sodio/uso terapéutico , Adulto , Femenino , Humanos , Síndromes de Neurotoxicidad/diagnóstico , Síndromes de Neurotoxicidad/tratamiento farmacológico , Síndromes de Neurotoxicidad/etiología , Pronóstico , Tasa de Supervivencia , Adulto JovenRESUMEN
Young males have a unique but rare predilection to develop mediastinal nonseminomatous germ cell tumors (NSGCTs) and concomitant acute megakaryoblastic leukemia (AMKL). Common cytogenetic and molecular abnormalities such as isochromosome 12p and somatic Tumor Protein P53(TP53) and Phosphatase And Tensin Homolog (PTEN) mutations have been reported in the presumed mutual neoplastic clones of origin. We report the case of a 17-year-old male who presented with a mediastinal NSGCT with high-grade sarcomatous transformation and a diagnosis of AMKL approximately 4 months later. Next-generation sequencing revealed identical KRAS Proto-Oncogene, GTPase (KRAS) p.Ala146Thr, TP53 p.Leu257Pro, and PTEN p.Leu181Pro missense mutations at similar variant allele frequencies in both the NSGCT and AMKL samples. Cytogenetic and microarray analyses detected shared copy gains in all chromosomes except chromosomes 9, 13, and Y. Multiple additional clonal chromosomal alterations were detected in the AMKL sample when compared with the NSGCT. This case emphasizes the shared clonal origins of these malignancies and identifies KRAS and other copy number alterations as potential molecular drivers in a subset of these combined diseases.
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Biomarcadores de Tumor/genética , Leucemia Megacarioblástica Aguda/patología , Neoplasias del Mediastino/patología , Neoplasias de Células Germinales y Embrionarias/patología , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias Testiculares/patología , Adolescente , Análisis Citogenético , Humanos , Leucemia Megacarioblástica Aguda/complicaciones , Leucemia Megacarioblástica Aguda/diagnóstico , Leucemia Megacarioblástica Aguda/genética , Masculino , Neoplasias del Mediastino/complicaciones , Neoplasias del Mediastino/diagnóstico , Neoplasias del Mediastino/genética , Mutación , Neoplasias de Células Germinales y Embrionarias/complicaciones , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/genética , Proto-Oncogenes Mas , Neoplasias Testiculares/complicaciones , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/genéticaRESUMEN
We report the case of a 3-year-old girl diagnosed with acute megakaryoblastic leukemia, who presented after >1 year of bilateral leg pain. At times the pain was severe enough to prevent ambulation, prompting visits to her primary care provider. However, it was not until acute respiratory failure occurred with subsequent hospitalization in the pediatric intensive care unit that severe anemia and thrombocytopenia were discovered and the diagnosis of acute myeloid leukemia was made. Bilateral lower extremity swelling was noted on admission and radiographs showed diffusely abnormal appearance of the long bones of her lower extremities with periosteal reaction and echogenic debris in the subperiosteal space, thought to represent leukemic cells. This case highlights the importance of recognizing atypical signs and symptoms of myelodysplastic syndrome progressing to acute leukemia in the context of abnormal bone pain and radiographic changes.
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Neoplasias Óseas , Leucemia Megacarioblástica Aguda , Periostio , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Preescolar , Femenino , Humanos , Leucemia Megacarioblástica Aguda/diagnóstico por imagen , Leucemia Megacarioblástica Aguda/metabolismo , Leucemia Megacarioblástica Aguda/patología , Extremidad Inferior , Periostio/diagnóstico por imagen , Periostio/metabolismo , Periostio/patologíaRESUMEN
Emergency departments (EDs) are alert to the possibility of stroke and the need for early interventions to improve long-term clinical outcomes. However, new-onset hemiparesis in pediatric patients with leukemia may be due to a number of different etiologies, including most common side effects from chemotherapeutic agents. We present a case of a 15-year-old boy with pre-B acute lymphoblastic leukemia on chemotherapy, having recently received a high-dose methotrexate infusion in addition to intrathecal methotrexate therapy, who presented to our ED with acute right-sided hemiparesis. He was initially suspected as having a possible ischemic stroke. Magnetic resonance imaging (diffusion-weighted and fluid-attenuated inversion recovery sequence) demonstrated focal areas of diffusion restriction, an early sign of delayed-onset methotrexate neurotoxicity. Our patient received appropriate supportive care and leucovorin rescue with gradual clinical recovery, after a prolonged hospitalization and acute care rehabilitation over the course of several months. Our case illustrates the need for ED providers to consider methotrexate neurotoxicity in pediatric oncology patients presenting with acute neurologic changes.
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Antimetabolitos Antineoplásicos/efectos adversos , Metotrexato/efectos adversos , Síndromes de Neurotoxicidad/diagnóstico , Paresia/inducido químicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Adolescente , Antídotos/uso terapéutico , Antimetabolitos Antineoplásicos/administración & dosificación , Encéfalo/patología , Imagen de Difusión por Resonancia Magnética , Humanos , Leucovorina/uso terapéutico , Masculino , Síndromes de Neurotoxicidad/etiología , Paresia/terapiaRESUMEN
Nearly 40 % of children with acute myeloid leukemia (AML) suffer relapse arising from chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcriptionâ 3). Herein, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects inâ vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML.
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Antineoplásicos/farmacología , Leucemia Mieloide Aguda/tratamiento farmacológico , Naftalenos/farmacología , Rodio/química , Factor de Transcripción STAT3/antagonistas & inhibidores , Sulfonamidas/farmacología , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Sitios de Unión/efectos de los fármacos , Catálisis , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Leucemia Mieloide Aguda/patología , Ratones , Naftalenos/química , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Factor de Transcripción STAT3/metabolismo , Relación Estructura-Actividad , Sulfonamidas/químicaRESUMEN
OBJECTIVES: To compare the timeline for post-operative quadriceps and hamstrings strength recovery following anterior cruciate ligament reconstruction (ACLR) using either a quadriceps tendon (QT) or hamstring tendon (HT) autograft. METHODS: Patients (≤18 years) who underwent ACLR using autograft QT or HT were included. Isokinetic strength was extracted at 3, 6, and 12 months post-operatively. Effects of time and graft type on quadriceps or hamstring limb symmetry index (qLSI/hLSI) was assessed with two-way repeated measures ANOVA. Between group differences at each time point were assessed with unpaired t-tests. Chi-square and Kaplan-Meir analysis analyzed the proportions of subjects able to achieve ≥90% LSI. RESULTS: A total of 75 subjects (QT n = 38 HT n = 37,15.8 years) were included. There were significant differences in qLSI, with greater symmetry within the HT group at all time points. A higher proportion of subjects with HT grafts were able to achieve ≥90% qLSI within 12 months of surgery (81% vs 45%, p = 0.001). CONCLUSION: Compared to those with HT autografts, adolescents with QT autografts demonstrate a prolonged timeline for quadriceps recovery. While mean strength values above 90% are achieved, a significantly lower percentage of QT patients are able to achieve 90% qLSI by 12 months post-op.
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Reconstrucción del Ligamento Cruzado Anterior , Autoinjertos , Tendones Isquiotibiales , Fuerza Muscular , Músculo Cuádriceps , Humanos , Reconstrucción del Ligamento Cruzado Anterior/rehabilitación , Adolescente , Masculino , Femenino , Fuerza Muscular/fisiología , Tendones Isquiotibiales/trasplante , Músculo Cuádriceps/fisiología , Recuperación de la Función , Lesiones del Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/fisiopatología , Trasplante Autólogo , AtletasRESUMEN
Levofloxacin prophylaxis reduces bloodstream infections in neutropenic patients with acute myeloid leukemia or relapsed acute lymphoblastic leukemia. A retrospective, longitudinal cohort study compares incidence of bacteremia, multidrug-resistant organisms (MDRO), and Clostridioides difficile (CDI) between time periods of levofloxacin prophylaxis implementation. Benefits were sustained without increasing MDRO or CDI.
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The survival rate of pediatric acute myeloid leukemia (pAML) is currently around 60%. While survival has slowly increased over the past few decades, the development of novel agents likely to further improve survival for this heterogeneous patient population has been limited by gaps in the pAML pre-clinical pipeline. One of the major hurdles in evaluating new agents for pAML is the lack of pAML patient-derived xenograft (PDX) models. Unlike solid tumors and other types of leukemias, AML is notoriously hard to establish in mouse models, likely due in part to the need for specific human microenvironment elements. Our laboratory at TCH/BCM addressed this gap by establishing a systematic PDX workflow, leveraging advanced immunodeficient hosts and capitalizing on our high volume of pAML patients and close coordination between labs and clinical sections. Patients treated at TCH are offered the chance to participate in specimen banking protocols that allow blood and bone marrow collection as well as the collection of relevant clinical data. All patients who consent and have samples available are trialed for PDX development. In addition, samples from the Children's Oncology Group (COG) are also trialed for PDX generation. Serially transplanting PDX models are validated using short tandem repeat (STR) and characterized using both targeted DNA/RNA next generation sequencing and RNAseq. As of March 2023, this systematic approach has resulted in 26 serially transplanting models. Models have been shared with requesting labs to facilitate external pAML pre-clinical studies. Available PDX models can be located through the BCM PDX Portal. We expect our growing PDX resource to make a significant contribution to expediting the testing of promising novel therapeutics for pAML.