Among boys with cerebral adrenoleukodystrophy, matched donors for allogeneic transplantation are available to only a few. Infusion of CD34+ autologous stem cells transduced with a lentiviral vector ...prevented neurologic deterioration in 15 of 17 boys with the disease.
Objectives
In critically ill, mechanically ventilated adults, diaphragmatic atrophy and reduced diaphragmatic thickening fraction (DTF) has been associated with poor extubation outcomes. ...Diaphragmatic ultrasound assessment in critically ill pediatric patients shows similar results, though studies are on‐going. We sought to explore the feasibility and utility of using DTF, obtained during a spontaneous breathing trial (SBT) in predicting weaning outcomes.
Methods
We conducted a prospective, observational study in a single‐center tertiary noncardiac pediatric intensive care unit (PICU) in a children's hospital. Mechanically ventilated pediatric patients were included except for those with preexisting conditions of neuromuscular weakness, diaphragm paresis, or chronic respiratory failure requiring non‐invasive or invasive mechanical ventilation at baseline. A convenience sample of 38 patients were included in the study.
Results
Weaning failure occurred in 10/38 (26%) instances with 9/38 (24%) occurring due to failed SBT and 1/38 (2%) due to failed extubation requiring reintubation. Median DTF was 24% (IQR: 12–33). DTF was significantly lower in instances of failed SBT, 12% compared to 27% (P < .01). The odds ratio (OR) of SBT failure utilizing: TF < 25% is 12 (CI: 1.33–108.0, Z‐score: 2.22, P = .027), TV <5 mL/kg was 10.4 (CI: 1.76–61.67, Z‐score: 2.58, P = .01), and combined TV <5 mL/kg and TF < 25% is 17.6 (CI: 1.19–259.61, Z‐score: 2.09, P = .04).
Conclusions
Our preliminary study suggests that ultrasound measurements of diaphragm thickening fraction during spontaneous breaths in mechanically ventilated pediatric patients may be a useful addition in predicting weaning readiness.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
To the Editor:
Al-Samkari et al. (April 14 issue)
1
report that mitapivat was efficacious in the treatment of pyruvate kinase deficiency, and they observed increases from baseline of at least 1.5 g ...per deciliter in the hemoglobin level in at least 40% of adult patients who had disease emanating from at least one missense
PKLR
mutation and who were not receiving regular red-cell transfusions. The authors indicated that “all prespecified patient subgroups (including those defined according to a baseline hemoglobin level of <8.5 or ≥8.5 g per deciliter and those defined according to previous splenectomy status) in the mitapivat group . . .
Severe combined immunodeficiency (SCID) results from defects in the differentiation of hematopoietic stem cells into mature T lymphocytes, with additional lymphoid lineages affected in particular ...genotypes. In 2014, the Primary Immune Deficiency Treatment Consortium published criteria for diagnosing SCID, which are now revised to incorporate contemporary approaches. Patients with typical SCID must have less than 0.05 × 109 autologous T cells/L on repetitive testing, with either pathogenic variant(s) in a SCID-associated gene, very low/undetectable T-cell receptor excision circles or less than 20% of CD4 T cells expressing naive markers, and/or transplacental maternally engrafted T cells. Patients with less profoundly impaired autologous T-cell differentiation are designated as having leaky/atypical SCID, with 2 or more of these: low T-cell numbers, oligoclonal T cells, low T-cell receptor excision circles, and less than 20% of CD4 T cells expressing naive markers. These patients must also have either pathogenic variant(s) in a SCID-associated gene or reduced T-cell proliferation to certain mitogens. Omenn syndrome requires a generalized erythematous rash, absent transplacentally acquired maternal engraftment, and 2 or more of these: eosinophilia, elevated IgE, lymphadenopathy, hepatosplenomegaly. Thymic stromal defects and other causes of secondary T-cell deficiency are excluded from the definition of SCID. Application of these revised Primary Immune Deficiency Treatment Consortium 2022 Definitions permits precise categorization of patients with T-cell defects but does not imply a preferred treatment strategy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Of 30 patients with severe sickle cell disease who were treated with gene-edited autologous hematopoietic stem and progenitor cells, 29 were free from vaso-occlusive crises for at least 12 ...consecutive months.
Of 35 patients with transfusion-dependent β-thalassemia treated with gene-edited autologous hematopoietic stem and progenitor cells, 32 had hemoglobin levels maintained without red-cell transfusions ...for at least 12 consecutive months.
Background
The incidence of secondary malignancies associated with busulfan exposure is considered low, but has been poorly characterized. Because this alkylating agent is increasingly utilized as ...conditioning prior to gene therapy in nonmalignant hematologic and related disorders, more precise characterization of busulfan's potential contribution to subsequent malignant risk is warranted.
Procedure
We conducted a literature‐based assessment of busulfan and subsequent late effects, with emphasis on secondary malignancies, identifying publications via PubMed searches, and selecting those reporting at least 3 years of follow‐up.
Results
We identified eight pediatric and 13 adult publications describing long‐term follow‐up in 570 pediatric and 2076 adult hematopoietic cell transplant (HCT) recipients. Secondary malignancies were reported in 0.5% of pediatric HCT recipients, with no cases of myelodysplastic syndrome (MDS) or acute myelocytic leukemia (AML). Fatal secondary malignancies were reported in 0.8% of 1887 evaluable adult HCT recipients, and an overall incidence of secondary malignancies of 4.8% was reported in a subset of 389 evaluable adult patients. We also reviewed long‐term results from eight publications evaluating lentiviral‐ and human promotor‐based HSC‐targeted gene therapy in 215 patients with nonmalignant conditions, in which busulfan/treosulfan monotherapy or busulfan/fludarabine was the only conditioning. Two malignancies were reported in patients with sickle cell disease (SCD), one of which was potentially busulfan‐related. No additional malignancies were reported in 173 patients with follow‐up of 5–12 years.
Conclusion
The incidence of busulfan‐related secondary malignancies is low, and likely to be substantially less than 1% in pediatric transplant recipients, especially those receiving busulfan monotherapy for nonmalignant conditions other than SCD.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Purpose
Multi-modality therapy has resulted in improved survival for childhood malignancies. The
Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and ...Young Adult Cancers
provide practitioners with exposure- and risk-based recommendations for the surveillance and management of asymptomatic survivors who are at least 2 years from completion of therapy. This review outlines the pathophysiology and risks for oral and dental late effects in pediatric cancer survivors and the rationale for oral and dental screening recommended by the Children’s Oncology Group.
Methods
An English literature search for oral and dental complications of childhood cancer treatment was undertaken via MEDLINE and encompassed January 1975 to January 2013. Proposed guideline content based on the literature review was approved by a multi-disciplinary panel of survivorship experts and scored according to a modified version of the National Comprehensive Cancer Network “Categories of Consensus” system.
Results
The Children’s Oncology Group oral-dental panel selected 85 relevant citations. Childhood cancer therapy may impact tooth development, salivary function, craniofacial development, and temporomandibular joint function placing some childhood cancer survivors at an increased risk for poor oral and dental health. Additionally, head and neck radiation and hematopoietic stem cell transplantation increase the risk of subsequent malignant neoplasms in the oral cavity. Survivors require routine dental care to evaluate for potential side effects and initiate early treatment.
Conclusions
Certain childhood cancer survivors are at an increased risk for poor oral and dental health. Early identification of oral and dental morbidity and early interventions can optimize health and quality of life.
Background
We undertook a study to determine the impact of Wiskott Aldrich Syndrome (WAS) and X-linked thrombocytopenia (XLT) and their therapies upon the health-related quality of life (HRQOL) of ...patients and their families.
Materials and Methods
We undertook a survey of patients and their families, who self-identified as having either WAS or XLT. We assessed the PedsQL™ 4.0, the parent proxy form, and the family impact module. These results were compared with normative data from previously published reports.
Results
Sixty-eight patients (29 patients completed both the PedsQL™ 4.0 and the parent proxy form; 21 completed only the PedsQL™ 4.0; and 18 completed only the parent proxy form) were included. In contrast to patient-reported outcomes, parents of patients who had a bone marrow transplant (BMT) reported that their children had better QOL scores compared with those who did not (82.6 vs. 73.3,
p
= 0.023). The QOL of patients vs. previously published normative data showed decreases in patient scores for psychosocial health (72.62 vs. 86.58,
p
= < 0.001), emotional functioning (69.91 vs. 82.64,
p
= < 0.001), social functioning (77.55 vs. 91.56,
p
= < 0.001), and school functioning (70.46 vs. 85.67,
p
= < 0.001). The family impact study revealed deficits in emotional, social, and cognitive functioning, communication, and worry.
Conclusion
These results show that patients with WAS/XLT are significantly impacted with respect to QOL. BMT offered a better QOL for patients according to parents, but not as reported by the patients. Future studies should incorporate QOL to provide more data and a better understanding of outcomes for long-term survivors and decision-making regarding BMT.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Lifelong immunosuppression is required for allograft survival after kidney transplantation but may not ultimately prevent allograft loss resulting from chronic rejection. We developed an approach ...that attempts to abrogate immune rejection and the need for post-transplantation immunosuppression in three patients with Schimke immuno-osseous dysplasia who had both T-cell immunodeficiency and renal failure. Each patient received sequential transplants of αβ T-cell–depleted and CD19 B-cell–depleted haploidentical hematopoietic stem cells and a kidney from the same donor. Full donor hematopoietic chimerism and functional ex vivo T-cell tolerance was achieved, and the patients continued to have normal renal function without immunosuppression at 22 to 34 months after kidney transplantation. (Funded by the Kruzn for a Kure Foundation.)
Three patients with Schimke immuno-osseous dysplasia who underwent sequential bone marrow and kidney transplantation continued to have normal renal function without immunosuppression at 22 to 34 months.
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