Neuroblastoma management in children is multimodal and depends on multiple factors, including the possibility of complete surgical resection. Image-defined risk factors (IDRFs) are used to assess the feasibility of primary surgery. We studied the changes in IDRFs after neoadjuvant chemotherapy for thoracic neurogenic tumors.

We performed a multicenter review of 27 patients presenting with unresectable thoracic neurogenic tumors. Patients received neoadjuvant chemotherapy, according to their risk group. IDRF at diagnosis and before surgery were retrospectively analyzed by a radiologist and a surgeon, blind to the initial assessment. Surgical and oncologic outcomes were reviewed.

None of the patients presented MYCN amplification, and 78 IDRFs were identified at diagnosis. Vascular IDRFs were the most frequent, with 28 vascular IDRFs detected in 18 patients, 22 of which disappeared after chemotherapy. Reductions of tumor volume were associated with a regression of IDRFs. Patients undergoing minimally invasive surgery had smaller tumor volumes than those undergoing open surgery, and no vascular IDRF. Two patients received two additional courses of chemotherapy to reduce tumor volume sufficiently for surgery. One patient with ganglioneuroblastoma underwent early surgery due to a lack of response to initial chemotherapy.

Tumor volume reduction with neoadjuvant chemotherapy eliminates most IDRF in thoracic neurogenic tumors. Vascular IDRF are rapidly resolved at this site, making surgical resection and minimally invasive surgery possible.

Tumor volume reduction with neoadjuvant chemotherapy eliminates most IDRF in thoracic neurogenic tumors. L-Ornithine L-aspartate supplier Vascular IDRF are rapidly resolved at this site, making surgical resection and minimally invasive surgery possible.

Patients with late, ≥18months postdiagnosis, isolated central nervous relapse (iCNS-R) of B-acute lymphoblastic leukemia (ALL) have excellent outcomes with chemotherapy plus cranial radiotherapy, with 5-year overall survival (OS) approaching 80% in POG 9412. Subsequent relapse and radiation-related morbidity remain the causes of treatment failure and long-term sequelae. COG AALL02P2 aimed to maintain outcomes in patients with late iCNS-R using intensified chemotherapy and a decrease in cranial irradiation from 1800 to 1200cGy.

COG AALL02P2 enrolled 118 eligible patients with B-cell ALL (B-ALL) and late iCNS-R who received intensified systemic therapy, triple intrathecal chemotherapy, and 1200cGy cranial irradiation delivered at 12months, with maintenance chemotherapy continuing until 104weeks postdiagnosis.

The 3-year event-free survival (EFS) and OS were 64.3% ± 4.5% and 79.6% ± 3.8%, with 46.1% (18/39) of second relapses including the CNS. Of the 112 patients who completed therapy, 78 received protocot plan. New approaches are needed to improve outcome for these patients and determine the optimal timing and dose of cranial radiation in the treatment of iCNS-R.TAFRO (thrombocytopenia, anasarca, fever/elevated C-reactive protein, reticulin myelofibrosis, renal dysfunction, and organomegaly) clinical subtype of idiopathic multicentric Castleman disease (iMCD-TAFRO) is a rare lymphoproliferative disease characterized by systemic inflammation. First-line treatment for iMCD-TAFRO includes steroids and interleukin (IL)-6 blockade. Many patients have refractory disease, which is associated with significant morbidity and mortality, and treatment remains challenging. We present two pediatric cases of iMCD-TAFRO. One patient responded to IL-6 blockade; the other was refractory to siltuximab and chemotherapy, ultimately responding to JAK inhibition with ruxolitinib. This is the first reported pediatric case of refractory iMCD-TAFRO responding to JAK inhibition.This short review focuses on enantiopure planar chiral [2.2]paracyclophanes (pCps), a fascinating class of molecules that possess an unusual three-dimensional core and intriguing physicochemical properties. In the first part of the review, different synthetic strategies for preparing optically active pCps are described. Although classical resolution methods based on the synthesis and separation of diastereoisomeric products still dominate the field, recent advances involving the kinetic resolution of racemic compounds and the desymmetrization of meso derivatives open up new possibilities to access enantiopure key intermediates on synthetically useful scales. Due to their advantageous properties including high configurational and chemical stability, [2.2]paracyclophanes are increasingly employed in various research fields, ranging from stereoselective synthesis to material sciences. The applications of [2.2]paracyclophanes in asymmetric organocatalysis are described in the second part of the review. While historically enantiopure pCps have been mainly employed by organic chemists as chiral ligands in transition-metal catalysis, these compounds can also be used as efficient catalysts in metal-free reactions and may inspire the development of new transformations in the near future.Microbial cell factories provide a sustainable and economical way to produce chemicals from renewable feedstocks. However, the accumulation of targeted chemicals can reduce the robustness of the industrial strains and affect the production performance. Here, the physiological functions of Mediator tail subunit CgMed16 at l-malate stress were investigated. Deletion of CgMed16 decreased the survival, biomass, and half-maximal inhibitory concentration (IC50 ) by 40.4%, 34.0%, and 30.6%, respectively, at 25 g/L l-malate stress. Transcriptome analysis showed that this growth defect was attributable to changes in the expression of genes involved in lipid metabolism. In addition, tolerance transcription factors CgUSV1 and CgYAP3 were found to interact with CgMed16 to regulate sterol biosynthesis and glycerophospholipid metabolism, respectively, ultimately endowing strains with excellent membrane integrity to resist l-malate stress. Furthermore, a dynamic tolerance system (DTS) was constructed based on CgUSV1, CgYAP3, and an l-malate-driven promoter Pcgr-10 to improve the robustness and productive capacity of Candida glabrata. As a result, the biomass, survival, and membrane integrity of C. glabrata 012 (with DTS) increased by 22.6%, 31.3%, and 53.8%, respectively, compared with those of strain 011 (without DTS). Therefore, at shake-flask scale, strain 012 accumulated 35.5 g/L l-malate, and the titer and productivity of l-malate increased by 32.5% and 32.1%, respectively, compared with those of strain 011. This study provides a novel strategy for the rational design and construction of DTS for dynamically enhancing the robustness of industrial strains.