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BackgroundPleuropulmonary blastoma (PPB) is the most common lung cancer of infancy and early childhood. Type I PPB is a purely cystic lesion that has a microscopic population of primitive small cells with or without rhabdomyoblastic features and may progress to type II or III PPB, whereas type Ir lacks primitive small cells.MethodsChildren with suspected PPB were enrolled in the International PPB/DICER1 Registry. Pathology was centrally reviewed, and follow-up was ascertained annually.ResultsBetween 2006 and 2022, 205 children had centrally reviewed type I or Ir PPB; 39% of children with type I and 5% of children with type Ir PPB received chemotherapy. Outcomes were favorable, although 11 children (nine with type I and two with type Ir PPB) experienced progression to type II/III (n = 8) or regrowth of type I PPB at the surgical site (n = 3), none of whom received chemotherapy before progression. Age and cyst size in combination were more suitable than either factor alone in predicting whether a particular lesion was type I or Ir PPB.ConclusionsFor young children with type I PPB, outcomes are favorable, but complete resection is indicated because of the risk for progression. Chemotherapy may be useful in a subset of children at increased risk for recurrence/progression. Efforts to risk stratify children with type I PPB to optimize outcomes while reducing treatment-related side effects are underway.

PurposePleuropulmonary blastoma (PPB) is the most common primary lung neoplasm of infancy and early childhood. Type II and type III PPB have historically been associated with a poor prognosis.MethodsPatients with known or suspected PPB were enrolled in the International PPB/DICER1 Registry. Medical records were abstracted with follow-up ascertained annually. All PPB diagnoses were confirmed by central pathology review. Beginning in 2007, the IVADo regimen (ifosfamide, vincristine, actinomycin-D, and doxorubicin) was recommended as a potential treatment regimen for children with type II and type III PPB. This regimen was compared with a historical control cohort.ResultsFrom 1987 to 2021, 314 children with centrally confirmed type II and type III PPB who received upfront chemotherapy were enrolled; 132 children (75 with type II and 57 with type III) received IVADo chemotherapy. Adjusted analyses suggest improved overall survival for children treated with IVADo in comparison with historical controls with an estimated hazard ratio of 0.65 (95% CI, 0.39 to 1.08). Compared with localized disease, distant metastasis at diagnosis was associated with worse PPB event-free survival and overall survival with hazard ratio of 4.23 (95% CI, 2.42 to 7.38) and 4.69 (95% CI, 2.50 to 8.80), respectively.ConclusionThe use of IVADo in children with type II and type III PPB resulted in similar-to-improved outcomes compared with historical controls. Inferior outcomes with metastatic disease suggest the need for novel therapies. This large cohort of uniformly treated children with advanced PPB serves as a benchmark for future multicenter therapeutic studies for this rare pediatric tumor.

Various wireless technologies were field-tested in a six-story laboratory building to identify wireless technologies that can scale for future DR applications through very low node density power consumption, and unit cost. Data analysis included analysis of the signal-to-noise ratio (SNR), packet loss, and link quality at varying power levels and node densities. The narrowband technologies performed well, penetrating the floors of the building with little loss and exhibiting better range than the wideband technology. 900 MHz provided full coverage at 1 watt and substantially complete coverage at 500 mW at the test site. 900 MHz was able to provide full coverage at 100 mW with only one additional relay transmitter, and was the highest-performing technology in the study. 2.4 GHz could not provide full coverage with only a single transmitter at the highest power level tested (63 mW). However, substantially complete coverage was provided at 2.4 GHz at 63 mW with the addition of one repeater node.

Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC) (1). It has previously been demonstrated that the absence of FHleads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions (2-4). However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fhl has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fhl-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fhl-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells nonviable, while sparing wild-type Fhl-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1deficiency, providing a new potential target for treating HLRCC patients., To study metabolic adaptation of FH-deficient cells we first generated immortalized kidney cells from mice homozygous for a conditionally targeted Fh1 allele (3). These cells contain LoxP sites flanking exons [...]