Outcome of Tocilizumab Treatment in Febrile Neutropenic Children with Severe Sepsis/Septic Shock in a Single-Center Retrospective Case Series.

PURPOSE: To assess the efficacy of an IL-6 blockade with tocilizumab on treatment outcome of severe sepsis/septic shock in children with febrile neutropenia. METHODS: We performed a retrospective study of febrile neutropenic patients younger than 18 years old who developed severe sepsis/septic shock at a single medical center between November 2022 and October 2023. RESULTS: Seven patients with febrile neutropenia complicated with severe sepsis/septic shock were identified. Four of seven patients received tocilizumab in addition to standard of care. The median IL-6 level before administration of tocilizumab was 14,147 pg/mL (range: 672-30,509 pg/mL). All four patients successfully recovered from severe sepsis/septic shock. Three of seven patients received standard of care without tocilizumab. IL-6 levels were checked intwo2 patients, with a median of 1514.5 (range: 838-2191). Only one of three (33%) patients without tocilizumab therapy made a full recovery from severe sepsis/septic shock. The mortality rate was higher in patients without tocilizumab therapy compared to patients with tocilizumab therapy (67% vs. 0%). CONCLUSIONS: Administration of tocilizumab reduced mortality of severe sepsis/septic shock in children with febrile neutropenia. However, it warrants confirmation with a larger number of patients and a longer follow-up.

Knowledge, Attitude, and Practice About Antibiotic Use and Antimicrobial Resistance Among Nursing Students in China: A Cross Sectional Study.

Purpose: The knowledge, attitude, and practices (KAP) concerning antibiotics by healthcare students have the potential impact on controlling antibiotic abuse and antimicrobial resistance (AMR) growth. This study aims to evaluate the levels and explore the associated factors with KAP on antibiotic use and AMR in Chinese nursing students. Methods: A cross-sectional survey using a self-administered questionnaire consisting of demographics and selected features and KAP on antibiotic use and AMR was conducted to measure KAP levels among nursing students at various universities in Hubei Province, China. The logistic regression analyses were performed to analyze the potential factors associated with the KAP. Results: The survey eventually included a total of 1959 nursing students. The mean scores for KAP were 57.89 ±26.32, 55.00 ±12.50, and 71.88 ±15.63, respectively. Regarding knowledge, 54.3% of participants were unaware that antibiotic was ineffective against viral infections. Regarding attitude, 36% of participants agreed that current antibiotic abuse existed; 96.2% of participants thought it necessary to set up a special course on antibiotics. Regarding practice, only 48.4% of participants usually purchased antibiotics with a prescription. Multivariable analyses indicated that lack of discussion on AMR in school courses was an independent risk factor against KAP, respectively. The main knowledge sources of antibiotic being outside the classroom was an independent risk factor related to knowledge and practice. The average score >80 points was an independent protective factor related to knowledge and practice. Conclusion: The KAP level on antibiotic use and AMR among Hubei nursing students was general and required further strengthening. Nursing students with risk factors should be prioritized in educational interventions. The findings of our study pointed out some directions for tailored interventions to improve the training on antibiotics.

Prediction of prognosis in patients with ischemic stroke combined with type 2 diabetes mellitus based on serum total bilirubin levels.

Serum bilirubin levels may have therapeutic benefits in oxidative stress-related diseases, but their role in stroke remains unclear. This study aimed to investigate the relationship between serum bilirubin levels on admission and clinical outcomes in ischemic stroke patients. We prospectively collected data from consecutive ischemic stroke admissions. Serum total bilirubin (TBIL) and direct bilirubin levels on admission were measured. Stroke severity at admission was assessed using the National Institutes of Health Stroke Scale, and functional status at discharge was evaluated using the modified Rankin scale. Among 180 patients, lower TBIL levels were observed in all 3 groups, with the mild group (7.89 ±â€…2.12 µmol/L) having lower levels than the moderate group (8.01 ±â€…2.12 µmol/L) and the severe group (9.12 ±â€…2.12 µmol/L). Although TBIL levels were initially associated with stroke severity, this relationship did not hold after adjusting for confounding factors. Serum bilirubin levels appear to be related to stroke severity but not independently associated with outcomes in ischemic stroke patients. Further research is needed to understand the underlying mechanisms of this relationship. There is a strong correlation between serum bilirubin levels and the severity and prognosis of ischemic stroke in patients with type 2 diabetes. Therefore, early control of serum TBIL and direct bilirubin is crucial for the treatment and prognosis of ischemic stroke in patients with type 2 diabetes.

Refining risk stratification in paediatric B-acute lymphoblastic leukaemia: Combining IKZF1plus and Day 15 MRD positivity.

This study investigates the potential utility of IKZF1 deletion as an additional high-risk marker for paediatric acute lymphoblastic leukaemia (ALL). The prognostic impact of IKZF1 status, in conjunction with minimal/measurable residual disease (MRD), was evaluated within the MRD-guided TPOG-ALL-2013 protocol using 412 newly diagnosed B-ALL patients aged 1-18. IKZF1 status was determined using multiplex ligation-dependent probe amplification. IKZF1 deletions, when co-occurring with CDKN2A, CDKN2B, PAX5 or PAR1 region deletions in the absence of ERG deletions, were termed IKZF1plus. Both IKZF1 deletion (14.6%) and IKZF1plus (7.8%) independently predicted poorer outcomes in B-ALL. IKZF1plus was observed in 4.1% of Philadelphia-negative ALL, with a significantly lower 5-year event-free survival (53.9%) compared to IKZF1 deletion alone (83.8%) and wild-type IKZF1 (91.3%) (p < 0.0001). Among patients with Day 15 MRD ≥0.01%, provisional high-risk patients with IKZF1plus exhibited the worst outcomes in event-free survival (42.0%), relapse-free survival (48.0%) and overall survival (72.7%) compared to other groups (p < 0.0001). Integration of IKZF1plus and positive Day 15 MRD identified a subgroup of Philadelphia-negative B-ALL with a 50% risk of relapse. This study highlights the importance of assessing IKZF1plus alongside Day 15 MRD positivity to identify patients at increased risk of adverse outcomes, potentially minimizing overtreatment.

microRNA-221 rescues the loss of dopaminergic neurons in a mouse model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is one of the most common systemic neurodegenerative diseases and is related to the loss of dopaminergic neurons in the substantia nigra. Several studies verified that microRNA (miRNAs) targeting the Bim/Bax/caspase-3 signaling axis is involved in the apoptosis of dopaminergic neurons in substantia nigra. In this study, we aimed to explore the role of miR-221 in PD. METHODS: To examine the function of miR-221 in vivo, we used a well-established 6-OHDA-induced PD mouse model. Then we conducted adenovirus-mediated miR-221 overexpression in the PD mice. RESULTS: Our results showed that miR-221 overexpression improved motor behavior of the PD mice. We demonstrated that overexpression of miR-221 reduced the loss of dopaminergic neurons in the substantia nigra striatum by promoting their antioxidative and antiapoptosis capacities. Mechanistically, miR-221 targets Bim, thus inhibiting Bim and Bax caspase-3 mediated apoptosis signaling pathways. CONCLUSION: Our findings suggest miR-221 participates in the pathological process of PD and might be a potential drug target and provide new insight into PD treatment.

Surgical treatment confers prognostic significance in pediatric malignant mediastinal germ cell tumors.

BACKGROUND: Primary malignant mediastinal germ cell tumors (GCTs) are rare pediatric tumors that have a poorer prognosis compared to GCTs occurring elsewhere in the body. The current study aimed to assess the prognostic factors and treatment outcomes of children with primary malignant mediastinal GCT in Taiwan. METHODS: The authors retrospectively reviewed children 0-18 years old who were newly diagnosed with primary malignant mediastinal GCT between January 1, 2005 and December 31, 2019 and were registered in the Taiwan Pediatric Oncology Group patient registry. The impact of presenting characteristics, including sex, age, tumor stage, histology subtype, surgical treatment, and chemotherapy regimens of the patients were analyzed. RESULTS: This study enrolled 52 children with malignant mediastinal GCT who had a median age of 16.0 (range, 6.0-17.9) years at diagnosis. The most common histological subtypes were mixed GCTs (n = 20) and yolk sac tumors (n = 15). Advanced disease stage and choriocarcinoma histology subtype were associated inferior outcomes. Children who received surgical treatment exhibited better outcomes compared to those who did not (5-year overall survival, 78% vs. 7%, p < .001). After comparing patients who received first-line cisplatin- and carboplatin-based chemotherapy, no difference in treatment outcomes was observed. Multivariate analysis showed that surgical management was the only independent predictor for superior OS. CONCLUSIONS: Surgical treatment is recommended for mediastinal GCT. Cisplatin-based chemotherapy was not superior to carboplatin-based chemotherapy as first-line treatment and may be avoided due to toxicity concerns.

NLRP3 inflammasome inhibitor ameliorates ischemic stroke by reprogramming the phenotype of microglia/macrophage in a murine model of distal middle cerebral artery occlusion.

Stroke is one of the leading causes of death and disability worldwide. NLRP3 inflammasome has an essential role in the neuropathology of stroke. Recent studies report that shifting the microglial M1 phenotype to the M2 phenotype protects against ischemic stroke. In the present study, the precise effects of Tranilast, a NLPR3 inflammasome inhibitor, on stroke were evaluated. We established a murine model of distal middle cerebral artery occlusion (dMCAO) and administered Tranilast to dMCAO-induced stroke mice. The NLRP3 level, caspase 1 activity, and infarct volume stroke mice were measured. The sensorimotor function, pro-inflammatory cytokine production, and M1/M2 marker expression were measured. The M1 phenotype was induced by treatment of BV2 microglia with lipopolysacharide and interferon γ, and these BV-2 cells were further treated with Tranilast. The expression of CD16 and CD206 was monitored. dMCAO increased the NLRP3 expression and enhanced caspase 1 activity. Tranilast treatment significantly decreased the infarct volume, improved sensorimotor function, and suppressed the production of inflammatory cytokines in stroke mice. Moreover, Tranilast decreased the M1 marker level while promoting the expression of M2 markers. In summary, our findings suggest that Tranilast ameliorates ischemic stroke through stimulating M2 polarization of microglia.

Betaine protects rats against ischemia/reperfusion injury-induced brain damage.

Brain ischemia and reperfusion (I/R) injury may lead to a poor prognosis for ischemic stroke, which could be alleviated by antioxidants with diminished oxidative stress. Betaine is a natural nutrient found in beetroot and seafood to improve cognitive performance in the elderly. The present study investigated whether betaine could protect the brain from I/R injury. Results showed that betaine treatment could reduce H2O2-induced cell death in the PC12 cell line. Pretreatment with betaine reduced the brain infarct volume and neuronal apoptosis in a rat I/R injury model induced by 2-h middle cerebral artery occlusion (MCAO). Biochemical analyses indicated that betaine treatment decreased proinflammatory cytokine production and reduced oxidative stress after I/R injury. Betaine increased the expression of antioxidative enzymes, such as glutathione peroxidase 4 (Gpx4) and superoxide dismutase 1 (Sod1), and antioxidative nonenzymatic genes, such as 3-mercaptopyruvate sulfurtransferase (Mpst), methionine sulfoxide reductases b1 (Msrb1), and Msrb2. These data suggest that betaine exerts a neuroprotective effect in I/R injury through enzymatic and nonenzymatic antioxidative systems and anti-inflammatory mechanisms.NEW & NOTEWORTHY These data suggested that betaine exerted a neuroprotective effect in I/R injury through enzymatic and nonenzymatic antioxidative systems.

Characteristics and outcomes of second cancers in patients with childhood cancer: A report from the Taiwan Pediatric Oncology Group.

BACKGROUND: Patients with childhood cancer are at increased risk for the development of second cancers. METHODS: A national multicenter survey of second cancers conducted by the Taiwan Pediatric Oncology Group retrieved retrospective data from the database at the Children Cancer Foundation in Taiwan beginning in 1995. The characteristics of second cancers and associations of patient demographic and clinical characteristics with time to death due to a second cancer were analyzed. RESULTS: We examined the records of 8782 patients with a primary cancer diagnosed between January 1, 1995 and December 31, 2013, and a total of 99 patients with a second cancer were identified. The most common type of second cancer was acute myeloid leukemia (n = 35), followed by acute lymphoblastic leukemia (n = 15), central nervous system (CNS) tumors (n = 15), and sarcomas (n = 10). Secondary hematological malignancies occurred earlier than other secondary cancers. The frequencies of second CNS tumors and second bone cancers and sarcomas were notably increased when prior radiation doses increased from zero, low dose to high dose. The overall 5-year survival of patients with a second cancer was poor (33.7%). Multivariate survival analysis revealed that the year of primary diagnosis ≤2002, secondary hematological malignancies, and age at second cancer diagnosis ≤9.3 years or >26.8 years increased the risk of death following second cancer. CONCLUSION: Children who develop a second cancer have an unfavorable outcome. Early detection and improved treatment for second cancers are needed.

Neuroprotective effects of microRNA 124 in Parkinson's disease mice.

BACKGROUND: Recent studies have revealed the close correlation between microRNAs (miRs) and Parkinson's disease (PD). Here, we aimed to investigate the neuroprotective effect of miR-124 in a PD mouse model. METHODS: MiR-124 expression in human plasma was detected by qRT-PCR. PD mouse model was established by stereotactic injection of 6-hydroxydopmine. Lentivirus were used to deliver and overexpress miR-124 and Axin1 into the substantia nigra. Multiple behavioral tests and oxidative stress assays were carried out to access the protective effect of miR-124 against PD. Western blot and luciferase assay were conducted to dissect the underlying molecular mechanisms. RESULTS: MiR-124 expression was decreased in PD patients. Overexpression of miR-124 in PD mice could improve motor defects, ameliorate dopaminergic neurons loss, and reduce oxidative stress. Mechanistically, miR-124 targeted Axin1 directly, and then attenuated PD progression via suppressing Axin1 and activating the Wnt/ß-catenin pathways in PD mice. CONCLUSION: MiR-124 is an important neuroprotective factor, which suppresses Axin1 and activates Wnt/ß-catenin signaling pathways in PD mice.

Comparison of Two Quantitative PCR-Based Assays for Detection of Minimal Residual Disease in B-Precursor Acute Lymphoblastic Leukemia Harboring Three Major Fusion Transcripts.

Two quantitative PCR (qPCR)-based methods, for clonal immunoglobulin or T-cell receptor gene (Ig/TCR) rearrangements and for fusion transcripts, are widely used for the measurement of minimal residual disease (MRD) in patients with B-precursor acute lymphoblastic leukemia (ALL). MRD of bone marrow samples from 165 patients carrying the three major fusion transcripts, including 74 BCR-ABL1, 54 ETV6-RUNX1, and 37 TCF3-PBX1, was analyzed by using the two qPCR-based methods. The correlation coefficient of both methods was good for TCF3-PBX1 (R2 = 0.8088) and BCR-ABL1 (R2 = 0.8094) ALL and moderate for ETV6-RUNX1 (R2 = 0.5972). The concordance was perfect for TCF3-PBX1 ALL (97.2%), substantially concordant for ETV6-RUNX1 ALL (87.1%), and only moderate for BCR-ABL1 ALL (70.6%). The discordant MRD, positive for only one method with a difference greater than one log, was found in 4 of 93 samples (4.3%) with ETV6-RUNX1, 31 of 245 samples (12.7%) with BCR-ABL1, and none of TCF3-PBX1 ALL. None of the eight non-transplanted patients with BCR-ABL1-MRD (+)/Ig/TCR-MRD (-) with a median follow-up time of 73.5 months had hematologic relapses. Our study showed an excellent MRD concordance between the two qPCR-based methods in TCF3-PBX1 ALL, whereas qPCR for Ig/TCR is more reliable in BCR-ABL1 ALL.

Oxidation Characteristics of Functional Groups in Relation to Coal Spontaneous Combustion.

To investigate and better understand the mechanism of coal spontaneous combustion, the distributions, evolution, and oxidation characteristics of functional groups in different coal samples were characterized using in situ Fourier transform infrared (FTIR) and electron paramagnetic resonance (EPR) experiments. The macroscopic characteristics of coal spontaneous combustion in relation to functional groups were also analyzed using the thermogravimetric/differential scanning calorimetry-FTIR coupling technique. The experimental results indicated that -OH was the most active groups of coal spontaneous combustion. It not only could react with the absorbed oxygen spontaneously but also found to be the main product of the chemisorption. Consequently, -OH was believed to contribute most both for the loss and increase of coal mass during the process of spontaneous combustion. Aliphatic hydrocarbons were the main components to form -C-O-O• and could be further oxidized into C=O. However, reactions between aliphatic hydrocarbons and oxygen were nonspontaneous. EPR experiments suggested that the tendency of coal spontaneous combustion acutely depended on the stability and survival time of free radicals. The more the stable and longer survival time of free radicals are, the lower the tendency of coal spontaneous combustion is.

Treatment outcomes of pediatric acute myeloid leukemia: a retrospective analysis from 1996 to 2019 in Taiwan.

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.

Malignant sacrococcygeal germ cell tumors in children in Taiwan: A retrospective single-center case series.

ABSTRACT: Although the incidence of malignant sacrococcygeal germ cell tumors (MSGCTs) is high in the East Asian countries, information about MSGCTs from this region is limited. This report aimed to analyze the data of children with MSGCTs in a single medical center in Taiwan.Patients aged 18 years or younger with primary MSGCTs or malignant recurrence of a sacrococcygeal teratoma who underwent surgery during the neonatal period between January 1999 and December 2016 were identified from the Linkou Chang Gung Cancer Center registry. The clinical features, laboratory data, and treatment outcomes were reviewed.Fifteen children (1 man and 15 women) with MSGCTs were identified. Sacrococcygeal tumors were present at birth in 7 patients. All patients presented with a bulging mass at the buttock region and they had normal alpha-fetoprotein levels at the time of diagnosis. They underwent primary excision of the tumor. Immature teratoma was histologically diagnosed in 5 neonates, and mature teratoma in 2. Only 1 patient with grade 3 immature teratoma received adjuvant chemotherapy. Two patients with mature teratoma developed malignant recurrence 1.6 and 2.1 years later, respectively. Eight patients were diagnosed with MSGCTs after the neonatal period. The common presenting symptoms included buttock asymmetry (37.5%), abdominal distension (25%), and constipation (12.5%). Seven patients had elevated alpha-fetoprotein levels for their age. They were administered neoadjuvant chemotherapy followed by tumor excision if a residual tumor was present. The histology of the excised tumor included mature teratoma (66.7%) and necrosis (33.3%). One patient with a normal alpha-fetoprotein level underwent primary tumor excision followed by adjuvant chemotherapy. Grade 2 immature teratoma with embryonal carcinoma was diagnosed histologically. Among the 15 patients with MSGCTs, 3 had a recurrence (at age of 2.1, 0.5, and 2.4 years, respectively) and 1 died (at age of 6.1 years) of disease progression. The 5-year overall and event-free survival rates were 90% and 80%, respectively.Children with MSGCTs had good overall prognoses in this case series. For those with sacrococcygeal mature teratoma or low-grade immature teratoma in the neonatal period, we recommend close follow-up for at least 3 years after surgery to detect malignant recurrence.

RAS pathway mutation is an added-value biomarker in pediatric Philadelphia-negative B-cell acute lymphoblastic leukemia with IKZF1 deletions.

BACKGROUND: IKZF1deletion is an unfavorable factor in Philadelphia negative (Ph -) B-cell acute lymphoblastic leukemia. However, the effects of IKZF1 deletions co-existing genetic alterations in Ph (-) ALL have not been extensively studied. METHODS: Bone marrow samples from 368 children with Ph (-) ALL were analyzed by using multiplex ligation-dependent probe amplification kit for detection of gene deletions and Sanger sequencing for mutational analysis of RAS pathway genes. The outcome was analyzed on 215 patients treated with Taiwan Pediatric Oncology Group-ALL-2002 protocol. RESULTS: IKZF1 deletions were present in 12.8% and IKZF1plus in 6.3% of patients. Mutations of RAS pathway genes were detected in 25.0% of IKZF1-deleted patients. The 10-year event-free survival (EFS) of IKZF1-undeleted patients was significantly better compared with IKZF1-deleted patients (80.0% vs. 47.8%, p = 0.001). Compared with outcome of patients harboring IKZF1 deletion alone, no difference in EFS was observed in patients with IKZF1plus , whereas three patients carried both IKZF1 and ERG deletions had a superior 10-year EFS (100%). The 10-year EFS of patients with any gene mutation of RAS pathway was worse than that of patients with wild-type genes (79.1% vs. 61.6%, p = 0.033). In multivariate analysis, RAS pathway mutations and IKZF1 deletion were independent predictors of inferior EFS. Co-existence of IKZF1 deletion with RAS pathway mutations had a worst 10-year EFS (11.1 ± 10.5%) and 10-year OS (53.3 ± 17.6%). CONCLUSIONS: Our results showed that RAS pathway mutation is an added-value biomarker in pediatric IKZF1-deleted Ph (-) ALL patients.

Cytogenetic aberration in mixed-phenotype acute leukemia in children: A single-center retrospective review.

BACKGROUND: Mixed-phenotype acute leukemia (MPAL) poses a diagnostic and therapeutic dilemma. No consensus exists on the strategy to assign patients with MPAL to either lymphoid- or myeloid-directed treatment. Thus, a better understanding of the characteristics of MPAL is a crucial unmet need. This study aims to provide information on a population-based cohort of children who received treatment based on standard, simple immunophenotypic criteria. METHODS: Single-center, retrospective clinical and laboratory reviews of patients with MPAL were provided by morphology, immunophenotyping, cytogenetics, and molecular methods. We identified 242 flow cytometry samples. Of all consecutive pediatric patients with acute leukemia, we identified 8 (3.3%) patients with MPAL fulfilling WHO 2016 criteria; these were classified as follows: B-lymphoid + myeloid (n = 4), T-lymphoid + myeloid (n = 2), and B + T-lymphoid (n = 2). RESULTS: Of 8 MPAL cases, 4 were boys and 4 girls [median age at diagnosis: 10.8 (range 1.1-17) years]. The b3a2 (p210) and e1a2 (p190) BCR/ABL fusion transcripts were detected in 1 patient with B/myeloid MPAL. Regarding the morphology, all patients were initially diagnosed as acute lymphoblastic leukemia, but no morphological characteristics or cytogenetic aberration was particularly predictive of an MPAL. Furthermore, 4 of 8 patients (50%) with MPAL were associated with chromosome 21 monosomy or partial trisomy. CONCLUSION: Despite no single recurrent chromosomal abnormality that could serve as a hallmark lesion in MPAL, cytogenetic alterations are frequent and predominantly associated with complex karyotype involving chromosome 21 abnormalities.

The influence of clinical features mimicking primary immunodeficiency diseases (mPID) on children with Langerhans cell histiocytosis (LCH) - Four with mPID among 39 LCH children from one referral center during 18-year period.

BACKGROUND: Recurrent or refractory infections can be a warning sign of primary immunodeficiency diseases (PID). Such mimicking PID (mPID) can occur in patients with Langerhans cell histiocytosis (LCH). Because some cases with refractory molluscum contagiosum-like lesions and persistent otorrhea are finally diagnosed with LCH, we wondered whether such mPID can occur in LCH children and affect on their prognosis. METHODS: We retrospectively reviewed all children with LCH at our institute from 2001 to 2018. A complete medical review of sex, age, symptoms, treatment course, and outcome comparison was performed. RESULTS: Of 39 enrolled LCH patients, three had persistent otorrhea and one had refractory molluscum contagiosum-like lesions despite aggressive antibiotic therapy. These four cases with mPID had significantly higher rates of multi-system involvement, recurrence and 5-month more lag time, but no risk organ (liver, spleen and bone marrow) involvement compared to those without mPID, although bone and skin were the most involved in both groups. Overall, the lag-time in multi-system was longer than that in single-system involvement (median 2.5 vs. 1.0 months; p = 0.003). The diagnosis-age of risk organ involvement was younger than those without (median 8 vs. 43 months; p = 0.004). There were no significant differences in diagnosis-age, single/multi-system and risk organ involvement between remission and recurrence groups. All were alive excluding four who were lost to follow-up. CONCLUSIONS: The LCH children with mPID had greater lag time, multi-system involvement, recurrence and more refractory treatment including transplantation despite the ratio of bone and skin lesions equal to those without mPID.

Daily decrease of post-operative alpha-fetoprotein by 9% discriminates prognosis of HCC: A multicenter retrospective study.

BACKGROUND: Mixed evidence challenges preoperative alpha-fetoprotein (AFP) as an independent prognostic factor for patients with hepatocellular carcinoma (HCC) after hepatectomy. RESULTS: Daily post-operative decrease of AFP by 9% as compared to the preoperative level (A09) were selected as the Cut-off. The Kaplan-Meier curve showed that A09 was significantly different for OS (P=0.043) and RFS (P=0.03). A decrease in risk by 54% was observed for OS and 32% for RFS in the at-risk population (A09>9%). A better concordance was observed after adding A09 into TNM and BCLC staging systems. Moreover, a consistent concordance was observed in the internal (FDZS5:0.63; FDZS3:0.608) and external (FDZS5:0.85; FDZS3:0.762) validation cohorts, suggesting its prognostic value in HCC population with elevated AFP. CONCLUSIONS: Decrease in perioperative serum AFP rather than preoperative AFP is an independent prognostic factor for HCC patients after hepatectomy. Cut-off A09 significantly discriminates overall and recurrence-free survival and could be interpret into TNM and BCLC staging systems to improve the stratification power for HCC patients with elevated AFP. METHODS: Kaplan-Meier curve depicted the differences of overall survival (OS) and recurrence-free survival (RFS). Nomogram and concordance were employed to evaluate the superiority of the current staging system.

Fisetin Prolongs Therapy Window of Brain Ischemic Stroke Using Tissue Plasminogen Activator: A Double-Blind Randomized Placebo-Controlled Clinical Trial.

Recombinant tissue plasminogen activator (rt-PA) can be utilized to treat ischemic stroke with safety and effectiveness but limited by a narrow therapeutic window. In the present clinical trial among patients with stroke, we sought to evaluate the potential of fisetin to extend the therapeutic window of rt-PA treatment. Patients with stroke were divided based on their onset-to-treatment time (OTT) and then randomly assigned to receive the rt-PA treatment combined with fisetin or placebo. Primary outcome was evaluated using the National Institutes of Health Stroke scale (NIHSS), and secondary outcome was assessed by serum levels of matrix metalloproteinase (MMP) 2, MMP 9, and C-reactive protein (CRP). Fisetin dramatically improved the treatment outcomes of the patients with stroke in the delayed OTT strata, as revealed by lower NIHSS scores. The beneficial effect of fisetin was likely attributable to reduced levels of MMP-2, MMP-9, and CRP in the serum, as evidenced by strong linear correlations between serum levels of such markers with the NIHSS scores in all enrolled patients. Fisetin may possess the potential to supplement traditional rt-PA treatments among patients with stroke, particularly for those with delayed OTT, and thereby extend the otherwise narrow therapeutic window and improve the treatment outcomes.