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Limited data are available on antimicrobials exposure and microbiology evolution in pediatric acute myeloid leukemia (AML) patients underwent antimicrobials prophylaxis. To assess the effectiveness of antimicrobials prophylaxis, antibiotic susceptibilities of bacteria, and exposure of antimicrobials during intensive chemotherapy for AML patients, 90 consecutive de novo AML patients aged 0–18 years between January 1, 1997 and March 31, 2018 were enrolled. Vancomycin, ciprofloxacin and voriconazole prophylaxis was administered from January 1, 2010. During the preprophylaxis period, January 1997 to December 2009, 62 patients experienced a total of 87 episodes of bloodstream infection (BSI) and 17 episodes of invasive fungal infection (IFI) among 502 courses of chemotherapy. In contrast, 16 episodes of BSI occurred and no IFIs were reported to occur in 28 patients who received 247 courses of chemotherapy in the prophylaxis period. Patients who received antimicrobial prophylaxis had a significant reduction of BSI, IFI, and febrile neutropenia in comparison with patients without prophylaxis. Exposure to amikacin, carbapenem, amphotericin B was reduced in the prophylaxis period. Imipenem susceptibility of Enterobacter cloacae as well as vancomycin susceptibility of Enterococcus species were reduced in the prophylaxis period. At the time of the last follow up, patients with prophylaxis had a better subsequent 5-year overall survival rate than those without prophylaxis. Prophylactic antimicrobials administration in children with AML who undergo chemotherapy can significantly reduce the rates of life-threatening infection, exposure to antimicrobials, and might result in a better outcome.

Pediatric extracranial germ cell tumors (GCTs) are rare, accounting for approximately 3.5% of childhood cancers. Since the introduction of platinum-based chemotherapy, the survival rate of patients has improved to more than 80%. However, poor-risk subtypes of pediatric extracranial GCTs do not respond well to chemotherapy, leading to refractory or relapsed (R/R) diseases. For example, long-term survival rates of mediastinal GCTs or choriocarcinoma are less than 50%. According to reports in recent years for adult patients with R/R GCTs, the use of high-dose chemotherapy (HDCT) combined with autologous stem cell transplantation (ASCT) has clinical advantages; however, HDCT combined with ASCT has rarely been reported in pediatric GCTs. The R/R and poor-risk groups of pediatric GCTs could benefit from HDCT and ASCT.

Primary intracranial ependymoma is a challenging tumor to treat despite the availability of multidisciplinary therapeutic modalities, including surgical resection, radiotherapy, and adjuvant chemotherapy. After the completion of initial treatment, when resistant tumor cells recur, salvage therapy needs to be carried out with a more precise strategy. Circulating tumor cells (CTCs) have specifically been detected and validated for patients with primary or recurrent diffused glioma. The CTC drug screening platform can be used to perform a mini-invasive liquid biopsy for potential drug selection. The validation of potential drugs in a patient-derived xenograft (PDX) mouse model based on the same patient can serve as a preclinical testing platform. Here, we present the application of a drug testing model in a six-year-old girl with primary ependymoma on the posterior fossa, type A (EPN-PFA). She suffered from tumor recurrence with intracranial and spinal seeding at 2 years after her first operation and extraneural metastases in the pleura, lung, mediastinum, and distant femoral bone at 4 years after initial treatment. The CTC screening platform results showed that everolimus and entrectinib could be used to decrease CTC viability. The therapeutic efficacy of these two therapeutic agents has also been validated in a PDX mouse model from the same patient, and the results showed that these two therapeutic agents significantly decreased tumor growth. After precise drug screening and the combination of focal radiation on the femoral bone with everolimus chemotherapy, the whole-body bone scan showed significant shrinkage of the metastatic tumor on the right femoral bone. This novel approach can combine liquid biopsy, CTC drug testing platforms, and PDX model validation to achieve precision medicine in rare and challenging tumors with extraneural metastases.

BackgroundThe direct comparison of molecular responses of front-line imatinib (IM) monitored at the same laboratory between children and adults with chronic phase (CP) of chronic myeloid leukaemia (CML) had not been reported. In this multicenter study, we compared the landmark molecular responses and outcomes of paediatric and adult CML-CP cohorts treated with front-line IM in whom the BCR::ABL1 transcript levels were monitored at the same accredited laboratory in Taiwan.MethodsBetween June 2004 and July 2020, 55 newly diagnosed paediatric and 782 adult CML-CP patients, with molecular diagnosis and monitoring at the same reference laboratory in Taiwan, were enrolled. The criteria of 2020 European LeukemiaNet were applied to evaluate the molecular responses.ResultsBy year 5, the cumulative incidences of IS <1%, MMR, MR4.0 and MR4.5 of paediatric patients were all significantly lower than those of adult patients (58 vs 75%, 48 vs 66%, 25 vs 44%, 16 vs 34%, respectively). The 10-year progression-free survival (PFS) (90%) and overall survival (OS) (94%) of paediatric patients did not differ from those (92%) of adult patients.ConclusionsWe demonstrated the paediatric cohort had slower molecular responses to front-line IM and similar outcomes in 10-year PFS and OS in real-world practice.

The factors that affect survival in patients with stage 4 neuroblastoma vary. Several prospective and retrospective studies have provided conflicting conclusions regarding the benefit of combining aggressive chemotherapy with complete surgical resection. We analyzed our experience to evaluate the effect of complete surgical resection of the primary tumor on survival when disseminated disease has been controlled by chemotherapy. We retrospectively reviewed the medical records of 44 consecutive children with neuroblastoma treated between 1990 and 2000. Twenty-six children with stage 4 disease were enrolled. Most were treated with surgical resection combined with chemotherapy. The survival rate was compared based on the timing (primary versus delayed until chemotherapy had been given) and results of surgery (complete tumor resection, microscopic residual disease, and gross residual disease). The mean survival (52.8 months) of children with delayed complete surgical resection (CSR) was statistically superior to that of those with microscopic residual (20.8 months, p = 0.0111) or gross residual tumor (12.2 months, p = 0.0141). In the CSR group, 1-, 2-, 3-, and 5-year survival rates were 88%, 77%, 77%, and 65%, respectively, vs. 80%, 40%, 20%, and 0% in the microscopic residual group. In conclusion, complete resection of the primary tumor with no residual disease was associated with improved survival in children with advanced neuroblastoma whose metastatic disease had been controlled by chemotherapy.

About 30% of neuroblastomas exhibit N-myc amplification. Neuroblastomas with Nmyc amplification tend to have a stroma-poor undifferentiated histopathologic phenotype and a high mitosis-karyorrhexis index (MKI). Karyorrhectic or pyknotic cells in neuroblastomas are closely related to apoptosis. Using fluorescence in situ hybridization (FISH) technique on formal in-fixed paraffin-embedded tissue, we conducted a retrospective study on 42 cases of neuroblastomas to investigate the relationship between N-myc amplification and apoptosis. The identification of apoptotic cells was based on morphology and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate (UTP)-biotin nick end labeling (TUNEL) method. Eleven (26%) of 42 tumors demonstrated N-myc amplification. After exclusion of nine tumors from patients who had prior chemotherapy, 3 3 tumors were available for thorough investigation. Based on the morphology of apoptotic cells, seven of the eight neuroblastomas with N-myc amplification had high apoptotic cell counts (more than 200 per 5,000 tumor cells), whereas only three of the 25 tumors without N-myc amplification revealed high apoptotic cells. Our results suggest that N-myc amplification can be readily detected in routinely processed tissue sections by FISH technique. Its presence has prognostic value and tends to be associated with a high number of apoptotic cells in neuroblastomas.

Improvement in outcomes of children with acute myeloid leukemia (AML) is attributed to several refinements in clinical management. We evaluated treatment outcomes of Taiwanese pediatric AML patients in the past 20 years. Overall, 860 de novo AML patients aged 0–18 years and registered in the Childhood Cancer Foundation of R.O.C during January 1996–December 2019 were included. Survival analysis was performed to identify factors that improved treatment outcomes. Regardless of treatment modalities used, patients during 2008–2019 had better 5-year event-free survival (EFS) and overall survival (OS) rates than patients during 1996–2007. For patients received the TPOG-AML-97A treatment, only 5-year OS rates were significantly different between patients diagnosed before and after 2008. Patients with RUNX1 – RUNX1T1 had similar relapse-free survival rates, but 5-year OS rates were better during 2008–2019. However, the survival of patients who received hematopoietic stem-cell transplantations (HSCT) did not differ significantly before and after 2008. For patients without relapse, the 5-year OS improved during 2008–2019. Non-relapse mortality decreased annually, and cumulative relapse rates were similar. In conclusion, 5-year EFS and OS rates improved during 2008–2019, though intensities of chemotherapy treatments were similar before and after 2008. Non-relapse mortality decreased gradually. Further treatment strategies including more intensive chemotherapy, novel agents’ use, identification of high-risk patients using genotyping and minimal residual disease, early intervention of HSCT, and antibiotic prophylaxis can be considered for future clinical protocol designs in Taiwan.

Background Methadone treatment was introduced in Taiwan in 2006 as a harm-reduction program in response to the human immunodeficiency virus (HIV), which is endemic among Taiwanese heroin users. The present study was aimed at examining the clinical and behavioral characteristics of methadone patients in northern Taiwan according to their HIV status. Methods The study was conducted at four methadone clinics. Participants were patients who had undergone methadone treatment at the clinics and who voluntarily signed a consent form. Between August and November 2008, each participant completed a face-to-face interview that included questions on demographics, risk behavior, quality of life, and psychiatric symptoms. Data on HIV and hepatitis C virus (HCV) infections, methadone dosage, and morphine in the urine were retrieved from patient files on the clinical premises, with permission of the participants. Results Of 576 participants, 71 were HIV positive, and 514 had hepatitis C. There were significant differences between the HIV-positive and HIV-negative groups on source of treatment payment, HCV infection, urine test results, methadone dosage, and treatment duration. The results indicate that HIV-negative heroin users were more likely to have sexual intercourse and not use condoms during the 6 months prior to the study. A substantial percent of the sample reported anxiety (21.0%), depression (27.2%), memory loss (32.7%), attempted suicide (32.7%), and administration of psychiatric medications (16.1%). There were no significant differences between the HIV-positive and HIV-negative patients on psychiatric symptoms or quality of life. Conclusions HIV-positive IDUs were comorbid with HCV, indicating the need to refer both HIV- and HCV-infected individuals for treatment in methadone clinics. Currently, there is a gap between psychiatric/psychosocial services and patient symptoms, and more integrated medical services should be provided to heroin-using populations.

Background This paper reports the psychometric properties of the Chinese version of Craving Beliefs Questionnaire (CCBQ), an easy-to-administer assessment instrument of measurement of craving beliefs for heroin abusers. Methods Participants were 445 heroin abusers from four methadone clinics in Northern Taiwan. Fifty-one of the participants were tested twice within a two-week period at a different hospital to examine test-retest reliability. Results Three-factor solution using principal component analysis was identified in the CCBQ: will power, compulsive behavior, and negative coping, accounting for 54.6% of the variance. Internal consistency analysis indicated that the three factors have strong reliability, with Cronbach alphas ranging from .81 to .92. The test-retest ICC coefficient is .80. The test-retest coefficients for the subscales will power, compulsive behavior, and negative coping are .76, .51, and .64, respectively. Overall, the data show that the CCBQ has acceptable reliability and validity, demonstrating that it can be a research instrument for assessing heroin craving beliefs. Conclusions The psychometric properties of the CCBQ seem promising for both research and clinical purposes, and the scale thus deserves further refinement and validation with heroin abusers.

Self-supervised learning (SSL) speech models have achieved remarkable performance in various tasks, yet the biased outcomes, especially affecting marginalized groups, raise significant concerns. Social bias refers to the phenomenon where algorithms potentially amplify disparate properties between social groups present in the data used for training. Bias in SSL models can perpetuate injustice by automating discriminatory patterns and reinforcing inequitable systems. This work reveals that prevalent SSL models inadvertently acquire biased associations. We probe how various factors, such as model architecture, size, and training methodologies, influence the propagation of social bias within these models. Finally, we explore the efficacy of debiasing SSL models through regularization techniques, specifically via model compression. Our findings reveal that employing techniques such as row-pruning and training wider, shallower models can effectively mitigate social bias within SSL model.