Embryonal rhabdomyosarcoma (ERMS) of the uterus has recently been shown to frequently harbor DICER1 mutations. Interestingly, only rare cases of extrauterine DICER1-associated ERMS, mostly located in the genitourinary tract, have been reported to date. Our goal was to study clinicopathologic and molecular profiles of DICER1-mutant (DICER1-mut) and DICER1-wild type (DICER1-wt) ERMS in a cohort of genitourinary tumors. We collected a cohort of 17 ERMS including nine uterine (four uterine corpus and five cervix), one vaginal, and seven urinary tract tumors. DNA sequencing revealed mutations of DICER1 in 9/9 uterine ERMS. All other ERMS of our cohort were DICER1-wt. The median age at diagnosis of patients with DICER1-mut and DICER1-wt ERMS was 36 years and 5 years, respectively. Limited follow-up data (available for 15/17 patients) suggested that DICER1-mut ERMS might show a less aggressive clinical course than DICER1-wt ERMS. Histological features only observed in DICER1-mut ERMS were cartilaginous nodules (6/9 DICER1-mut ERMS), in one case accompanied by foci of ossification. Recurrent mutations identified in both DICER1-mut and DICER1-wt ERMS affected KRAS, NRAS, and TP53. Copy number analysis revealed similar structural variations with frequent gains on chromosomes 2, 3, and 8, independent of DICER1 mutation status. Unsupervised hierarchical clustering of array-based whole-genome DNA methylation data of our study cohort together with an extended methylation data set including different RMS subtypes from genitourinary and extra-genitourinary locations (n = 102), revealed a distinct cluster for DICER1-mut ERMS. Such tumors clearly segregated from the clusters of DICER1-wt ERMS, alveolar RMS, and MYOD1-mutant spindle cell and sclerosing RMS. Only one tumor, previously diagnosed as ERMS arising in the maxilla of a 6-year-old boy clustered with DICER1-mut ERMS of the uterus. Subsequent sequencing analysis identified two DICER1 mutations in the latter case. Our results suggest that DICER1-mut ERMS might qualify as a distinct subtype in future classifications of RMS.

BackgroundThe standard treatment of fever in chemotherapy‐induced neutropenia (FN) includes emergency hospitalization and empirical intravenous antimicrobial therapy. This study determined if first‐day step‐down to oral outpatient treatment is not inferior to continued standard regarding safety and efficacy in children with low‐risk FN.ProcedureIn a randomized controlled non‐blinded multicenter study, pediatric patients with FN after non‐myeloablative chemotherapy were reassessed after 8–22 hours of inpatient intravenous antimicrobial therapy. Low‐risk patients were randomized to first‐day step‐down to experimental (outpatient, oral amoxicillin plus ciprofloxacin) versus continued standard treatment. Exact non‐inferiority tests were used for safety (no serious medical complication; non‐inferiority margin of difference, 3.5%) and efficacy (resolution of infection without recurrence, no modification of antimicrobial therapy, no adverse event; 10%).ResultsIn 93 (26%) of 355 potentially eligible FN episodes low‐risk criteria were fulfilled, and 62 were randomized, 28 to experimental (1 lost to follow‐up) and 34 to standard treatment. In intention‐to‐treat analyses, non‐inferiority was not proven for safety [27 of 27 (100%) vs. 33 of 34 (97%; 1 death) episodes; 95% upper confidence border, 6.7%; P = 0.11], but non‐inferiority was proven for efficacy [23 of 27 (85%) vs. 26 of 34 (76%) episodes; 95% upper confidence border, 9.4%; P = 0.045]. Per‐protocol analyses confirmed these results.ConclusionsIn children with low‐risk FN, the efficacy of first‐day step‐down to oral antimicrobial therapy with amoxicillin and ciprofloxacin in an outpatient setting was non‐inferior to continued hospitalization and intravenous antimicrobial therapy. The safety of this procedure, however, was not assessable with sufficient power. Pediatr Blood Cancer 2012;59:423–430. © 2012 Wiley Periodicals, Inc.

The collectin surfactant protein D (SP-D) is an important component of the pulmonary innate host defence. Up to now, little is known about the regulation of eosinophil function by SP-D. Various murine models of pulmonary hypersensitivity suggest that SP-D may be a potent anti-allergic protein. We investigated the modulation of eosinophil chemotaxis and degranulation by human SP-D. SP-D markedly inhibited the chemotaxis of eosinophils triggered by eotaxin, a major tissue-derived CC-chemokine, as shown in a modified Boyden chamber assay. In addition, degranulation of ECP in response to Ca2+ ionophore, immobilized IgG and serum from allergic patients was inhibited by SP-D. In a fixed-cell enzyme linked immunosorbent assay and in flow cytometry, SP-D bound to eosinophils. This binding was saturable and was inhibited by the addition of maltose and ethylenediaminetetraacetic acid, suggesting the involvement of the carbohydrate recognition domain of SP-D. In addition, flow cytometry showed significant interaction of SP-D with CD32 (FcgammaII receptor) on eosinophils, which might explain the inhibitory effect of SP-D on the IgG and serum-triggered eosinophil cationic protein degranulation of eosinophils. Our data further support the concept of an anti-inflammatory function of SP-D in the lung of patients with allergic diseases.

Purpose Pediatric patients with cancer are at high risk for severe infections. Infections can trigger changes of vital signs long before clinical symptoms arise. Continuous recording may detect such changes earlier than discrete measurements. We aimed to assess the feasibility of continuous recording of vital signs by a wearable device (WD) in pediatric patients undergoing chemotherapy for cancer. Methods In this prospective, observational single-center study, pediatric patients under chemotherapy wore the Everion® WD for 14 days. The predefined patient-specific goal was heart rate recorded in good quality during ≥18/24 h per day, on ≥7 consecutive days. The predefined criterion to claim feasibility was ≥15/20 patients fulfilling this patient-specific goal. Results Twenty patients were included (median age, 6 years; range, 2–16). Six patients aged 3–16 years fulfilled the patient-specific goal. Quality of heart rate recording was good during 3992 of 6576 (61%) hours studied and poor during 300 (5%) hours, and no data was recorded during 2284 (35%) hours. Eighteen of 20 participants indicated that this WD is acceptable to measure vital signs in children under chemotherapy. Conclusion The predefined feasibility criterion was not fulfilled. This was mainly due to important compliance problems and independent of the WD itself. However, continuous recording of vital signs was possible across a very wide age range in pediatric patients undergoing chemotherapy for cancer. We recommend to study feasibility in the Everion® again, plus in further WDs, applying measures to enhance compliance. Trial registration ClinicalTrials.gov (NCT04134429) on October 22, 2019.