Analysis of the incidence, characteristics, and risk factors of complications during induction chemotherapy in children with high-risk neuroblastoma.

Patients with high-risk neuroblastoma (HR-NB) exhibit suboptimal 5-year survival rates, leading to a widespread international preference for high-intensity chemotherapeutic regimens in these children. We analyzed the incidence and risk factors for complications during induction chemotherapy in children with HR-NB and tried to assist clinicians in predicting such complications and optimizing therapeutic strategy. The clinical data of children with HR-NB admitted to our hospital from January 2007 to December 2019 were retrospectively analyzed. The incidence, characteristics, and risk factors of complications (infection, hemorrhage, and chemotherapy-related adverse reactions (CRAR)) requiring hospitalization during induction chemotherapy in these children were explored. (1) A total of 108 patients with HR-NB were included in the final analysis. The overall infection rate was 92.6% (100/108), with the highest incidence of 71.3% observed during the first cycle. FN, bacterial infection, as well as fungal infection were common infectious complications in children with HR-NB during induction chemotherapy. (2) The overall hemorrhage rate was 24.1% (26/108), with the highest incidence of 14.8% also observed in the first cycle. Among the children with hemorrhage, there were 72% with bone marrow involved, while 65.0% of them had a high vanillylmandelic acid (VMA) value. And children with hemorrhage also exhibited neuron-specific enolase (NSE) ≥ 200 µg/L in 88.5% of cases and lactic dehydrogenase (LDH) ≥ 1000U/L in 73.1% of cases. (3) The incidence of CRAR rate was 100%, and 99.1% (107/108) patients experienced myelosuppression. The incidence of myelosuppression peaked in the third cycle, reaching up to 85.2%. Most children suffered severe myelosuppression existed with bone marrow metastases (76.3%), abnormal VMA (67.5%), and LDH ≥ 1000 U/L (60%). (4) Non-myelosuppressive adverse effects were observed in 75.9% children (82/108), with the highest incidence occurring in the third cycle at 42.6%. (5) Patients who experienced three types of complications had a lower median survival time (MST) of 54.4 months, a 3-year event-free survival (EFS) rate of (44.2 ± 10.7)%, and a 3-year overall survival (OS) rate of (75.8 ± 8.6)%, in comparison to those with only one or two complications, who had a higher MST of 59.5 months, a 3-year EFS rate of (73.5 ± 5.2)% (X2 = 10.457, P = 0.001), and a 3-year OS rate of (84.8 ± 4.1)% (X2 = 10.511, P = 0.001). CONCLUSION: The presence of bone marrow involved and increased VMA were high-risk factors for infection, while NSE ≥ 200 µg/L and LDH ≥ 1000 U/L were high-risk factors for hemorrhage. For those children who had experienced severe myelosuppression, the presence of bone marrow metastases, increased VMA, and LDH ≥ 1000 U/L were their risk factors. The presence of bone involvement was a high-risk factor for children to have non-myelosuppressive adverse effects. Complications that arise during induction chemotherapy could negatively impact the children's prognosis and overall quality of life. WHAT IS KNOWN: • The high-risk neuroblastoma (HR-NB) had a worse prognosis; there was a general international preference for high-intensity chemotherapeutic regimens in the induction phase to these children. WHAT IS NEW: • We analyzed the incidence and risk factors of complications during induction chemotherapy in children with HR-NB and tried to help clinicians predict such complications and adopt optimized therapeutic strategy.

A nomogram for predicting recurrence-free survival of intermediate and high-risk neuroblastoma.

This study aimed to confirm the independent risk factors for recurrence-free survival (RFS) in intermediate and high-risk neuroblastoma (NB) patients and set up an effective nomogram model for predicting the recurrence of NB. A total of 212 children with intermediate- and high-risk neuroblastoma, who had ever achieved complete remission (CR) or very good partial remission (VGPR) after standardized treatment in this hospital, were chosen as study objects. After retrospective analysis of the clinical data, Cox regression model was used to explore the factors related to the recurrence of neuroblastoma, to determine the variables to construct the Nomogram. The consistency index would predict the accuracy of this nomogram. RFS rate in 1-year, 3-year, 5-year, and 10-year was 0.811, 0.662, 0.639, and 0.604, respectively. Children with MYCN amplification had a higher neuron-specific enolase (NSE) value (P = 0.031) at the initial diagnosis than MYCN non-amplification. The univariate analysis predicted that increased vanillylmandelic acid (VMA) and NSE value and dehydrogenase (LDH) > 1000 U/L were important adverse factors for the recurrence of NB. Multivariate analysis demonstrated that age at diagnosis, tumor localization, MYCN state, histologic subtype, and tumor capsule were significantly associated with RFS (all P values < 0.05). Nomograms were established for predicting the recurrence of NB according to the Cox regression analysis. Internal verification by the Bootstrap method showed that the prediction of the nomogram's consistency index (C-index) was 0.824 (P = 0.023).   Conclusion: Age at diagnosis, tumor localization, MYCN state, histologic category, and tumor capsule were independent risk factors for the recurrence of NB. The nomogram model could accurately predict the recurrence of children with neuroblastoma. What is Known: • The prognoses of neuroblastoma (NB) could vary greatly due to the high heterogeneity, the 5-year survival rate of low-risk NB exceeded 90%, while the 5-year survival rate of children in the intermediate and high-risk groups was not satisfactory.. What is New: • Increased vanillylmandelic acid (VMA) and neuron-specific enolase (NSE) value, and lactate dehydrogenase (LDH)>1000U/L were important adverse factors for the recurrence of NB. • NSE value was more valuable for predicting NB recurrence.

Exploring the prognosis of neuroblastoma in adolescents and adults: a case series and literature review.

Neuroblastoma (NB) is one of the most common extracranial malignant solid tumors in childhood, and over 90% of NBs are diagnosed in children under the age of 10 years old. For patients between 14 and 18 years old or older than 18 years, due to the rarity of NB, few studies have been performed in this population. Defined "adolescent cases" as individuals in 14-18 years old and "adult cases" as older than 18 years old, we reported five NB cases of adolescents and adults in our hospital. 137 cases presented a review of published literature on this topic. Clinicopathological factors and treatment modalities used of the 142 patients were assessed for their prognostic value. Better outcomes were found in adolescent patients rather than adult patients (p=0.012). Patients diagnosed with neuroblastoma or ganglioneuroblastoma (nodular type) (p=0.006) and with distant metastasis (p<0.001) were characterized by poor outcomes. Distant metastasis was an independent adverse influencing factor for overall survival in adolescent and adult NB patients. Regarding treatment modalities, complete surgical resection was a significant factor improving the survival for such patients (p<0.001). For patients with distant metastasis, a significantly longer progression-free survival with chemotherapy than without chemotherapy (p=0.038), whereas chemotherapy did not show an advantage on patients with localized disease (p=0.039). The prognosis of NB in adolescent and adult patients was worse than that in children. These two groups also showed heterogeneity in clinical factors, genetic factors, and treatment tolerance. The rarity of adolescent and adult NB can lead to misdiagnosis and incorrect management. Further optimization of chemotherapy regimens and dosage for adolescent and adult NB patients is needed. The anti-GD2 immunotherapy may be an effective approach for treatment.

CTRL: Closed-Loop Transcription to an LDR via Minimaxing Rate Reduction.

This work proposes a new computational framework for learning a structured generative model for real-world datasets. In particular, we propose to learn a Closed-loop Transcriptionbetween a multi-class, multi-dimensional data distribution and a Linear discriminative representation (CTRL) in the feature space that consists of multiple independent multi-dimensional linear subspaces. In particular, we argue that the optimal encoding and decoding mappings sought can be formulated as a two-player minimax game between the encoder and decoderfor the learned representation. A natural utility function for this game is the so-called rate reduction, a simple information-theoretic measure for distances between mixtures of subspace-like Gaussians in the feature space. Our formulation draws inspiration from closed-loop error feedback from control systems and avoids expensive evaluating and minimizing of approximated distances between arbitrary distributions in either the data space or the feature space. To a large extent, this new formulation unifies the concepts and benefits of Auto-Encoding and GAN and naturally extends them to the settings of learning a both discriminative and generative representation for multi-class and multi-dimensional real-world data. Our extensive experiments on many benchmark imagery datasets demonstrate tremendous potential of this new closed-loop formulation: under fair comparison, visual quality of the learned decoder and classification performance of the encoder is competitive and arguably better than existing methods based on GAN, VAE, or a combination of both. Unlike existing generative models, the so-learned features of the multiple classes are structured instead of hidden: different classes are explicitly mapped onto corresponding independent principal subspaces in the feature space, and diverse visual attributes within each class are modeled by the independent principal components within each subspace.

scSensitiveGeneDefine: sensitive gene detection in single-cell RNA sequencing data by Shannon entropy.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) is the most widely used technique to obtain gene expression profiles from complex tissues. Cell subsets and developmental states are often identified via differential gene expression patterns. Most of the single-cell tools utilized highly variable genes to annotate cell subsets and states. However, we have discovered that a group of genes, which sensitively respond to environmental stimuli with high coefficients of variation (CV), might impose overwhelming influences on the cell type annotation. RESULT: In this research, we developed a method, based on the CV-rank and Shannon entropy, to identify these noise genes, and termed them as "sensitive genes". To validate the reliability of our methods, we applied our tools in 11 single-cell data sets from different human tissues. The results showed that most of the sensitive genes were enriched pathways related to cellular stress response. Furthermore, we noticed that the unsupervised result was closer to the ground-truth cell labels, after removing the sensitive genes detected by our tools. CONCLUSION: Our study revealed the prevalence of stochastic gene expression patterns in most types of cells, compared the differences among cell marker genes, housekeeping genes (HK genes), and sensitive genes, demonstrated the similarities of functions of sensitive genes in various scRNA-seq data sets, and improved the results of unsupervised clustering towards the ground-truth labels. We hope our method would provide new insights into the reduction of data noise in scRNA-seq data analysis and contribute to the development of better scRNA-seq unsupervised clustering algorithms in the future.

Anti-tumor effect of Huaier extract against neuroblastoma cells in vitro.

Huaier extract, the main active constituent proteoglycan, has anti-tumor activity in various experimental and clinical settings. However, the potential anti-neuroblastoma and associated mechanisms have not been investigated. Therefore, in this study, we aimed to elucidate the potential role of Huaier extract in 3 human neuroblastoma cell lines. Our study demonstrated that incubation with Huaier extract resulted in a marked decrease in cell viability in a dose-dependent manner. Huaier extract induced cell cycle arrest at G0/G1 phase in neuroblastoma and decreased the cell cycle related protein expression of cyclin D3. Western blotting analysis also showed that Huaier extract induced neuroblastoma cell apoptosis and autophagy. Signaling analysis indicated that Huaier extract suppressed the MEK/ERK and mTOR signaling pathways simultaneously. In conclusion, we verify that Huaier extract causes cell proliferation inhibition, apoptosis, autophagy, and cell cycle arrest in G0/G1 phase via MEK/ERK and mTOR signaling. Huaier extract may act as a complementary agent for treating neuroblastoma.

Anti-tumor effect of AZD8055 against neuroblastoma cells in vitro and in vivo.

Neuroblastoma (NB) is one of the most common solid tumors in children. High-risk NB remains lethal in about 50% of patients despite comprehensive and intensive treatments. Activation of PI3K/Akt/mTOR signaling pathway correlates with oncogenesis, poor prognosis and chemotherapy resistance in NB. Due to its central role in growth and metabolism, mTOR seems to be an important factor in NB, making it a possible target for NB. In this study, we investigated the effect of AZD8055, a potent dual mTORC1-mTORC2 inhibitor, in NB cell lines. Our data showed that mTOR signaling was extensively activated in NB cells. The activity of mTOR and downstream molecules were down-regulated in AZD8055-treated NB cells. Significantly, AZD8055 effectively inhibited cell growth and induced cell cycle arrest, autophagy and apoptosis in NB cells. Moreover, AZD8055 significantly reduced tumor growth in mice xenograft model without apparent toxicity. Taken together, our results highlight the potential of mTOR as a promising target for NB treatment. Therefore, AZD8055 may be further investigated for treatment in clinical trials for high risk NB.

Cisplatin-induced Ototoxicity in Children With Solid Tumor.

Cisplatin is the principal chemotherapeutic agent and also tremendously increases the survival for pediatric patients with neuroblastoma or hepatoblastoma. With the extended overall survival period, clinical medical workers and parents gradually attach more attention to the late effect of chemotherapy of these children. The purpose of this study is to analyze the incidence and risk factors of cisplatin-based hearing loss. We retrospectively collected the archives of cisplatin-based chemotherapy and audiometric evaluation from 2005 through 2017 at Xinhua Hospital. From 384 patients treated with cisplatin, full data of 59 patients were available, and 14 cases (23.7%) were identified as significant hearing loss. The median time from usage of platinum compounds to the most recent audio test was 406 days. Cumulative and single maximum cisplatin dose was 622.6±283.2 and 137.6±51.6 mg/m/cycle, respectively. Accumulated cisplatin dose (95% confidence interval, 1.001-1.006; P=0.012) and single maximum cisplatin dose (95% confidence interval, 1.000-1.029; P=0.049) were independently important predictors for moderate to severe hearing loss in children treated with cisplatin. Cisplatin can cause ototoxicity which profoundly handicap language development and social communication for children. Regular audiological management and long-term follow-up are strongly recommended for this vulnerable group.

Analysis of Recurrent Sacrococcygeal Teratoma in Children: Clinical Features, Relapse Risks, and Anorectal Functional Sequelae.

BACKGROUND Sacrococcygeal teratoma (SCT) is a relatively uncommon tumor. Recurrence with poor survival and anorectal dysfunction are the 2 leading problems for patients. Here, we would review the clinic features of patients with SCTs in our hospital to identify risk factors of recurrent SCTs and to analyze anorectal functional sequelae. MATERIAL AND METHODS A retrospective review of all patients with SCTs in our center between 2007 and 2013 was performed. We analyzed the recorded data on each patient and performed follow-up through phone calls. RESULTS Our study included 105 inpatients (78 girls and 27 boys); 104 cases underwent surgical resection, and 62.5% cases had a mature histopathology. The proportion of malignant teratomas rose with increasing age. Fifteen children developed recurrent SCTs with a median of 11.5 months, and most of them had an elevation of AFP levels. Four recurrent children experienced a second tumor relapse. We observed a statistically significant difference in survival rate through Kaplan-Meier method between relapsed (66.7%) and non-relapsed (94.4%) patients. In univariate analysis, incomplete primary resection and malignant histology were proven to increase recurrence risks. Nearly half of patients had at least 1 of the parameters reflecting abnormal bowel function (e.g., involuntary bowel movements, fecal incontinence, and constipation). For those recurrent SCTs patients, difficulty defecating was a major problem. CONCLUSIONS Tumor recurrence affected the prognosis of children with SCT. In our research, incomplete resection and malignant histology were considered risk factors. Constipation was the main problem in anorectal functional sequelae for children who had recurrence.

Treatment outcome of young children with acute lymphoblastic leukaemia: achievements and directions implied from Shanghai Children's Medical Centre based SCMC-ALL-2005 protocol.

This multicenter study used the Shanghai Children's Medical Center (SCMC)-ALL-2005 protocol for treatment of young patients (<2 years old) with acute lymphoblastic leukaemia (ALL), which was designed to improve treatment outcome in Chinese paediatric patients. These aims were pursued through risk-directed stratification based on presenting clinical and genetic features, minimal residual disease (MRD) levels and treatment response. All the patients achieved completed remission with 5-year event-free survivals of 82·6 ± 9·7% (low risk), 52·6 ± 8·4% (intermediate risk), 28·6 ± 17·1% (high risk). Disease recurrence was detected in bone marrow, bone marrow plus testis, testis alone and central nervous system in 16 (24·2%), 1 (1·5%), 1 (1·5%) and 1 (1·5%) patients respectively. No deaths were reported during induction. The SCMC-ALL-2005 trial for ALL patients <2 years old indicated high remission induction and low infection and treatment-related mortality rates.

Diffuse infantile hepatic hemangioma successfully treated with propranolol orally: a case report and literature review.

Background: Infantile hepatic hemangioma (IHH) is a common vascular, fast-growing hepatic tumor that is usually accompanied by multiple cutaneous hemangiomas. Diffuse IHH (DIHH) is a rare type of IHH that exhibits many tumors with nearly complete hepatic parenchymal replacement. At present, there is no specific standardized treatment plan for DIHH. Herein, we present the case of a 2-month-old girl with DIHH and without cutaneous hemangioma who achieved complete remission after undergoing propranolol monotherapy. Case presentation: The infant with low birth weight was presented to the pediatric department with a 2-month history of persistent vomiting and feeding difficulty. Ultrasonography and abdominal magnetic resonance imaging revealed hepatomegaly and diffused intrahepatic lesions. A computed tomography-guided percutaneous liver biopsy was performed, and the pathological examination suggested the diagnosis was DIHH. The patient exhibited remarkably response to an increasing dose of oral propranolol, from 0.5 mg/kg to 2 mg/kg every day. The intrahepatic lesions were almost completely regressed after one year of treatment and no distinct adverse reaction was observed. Conclusion: DIHH can induce life-threatening complications that require prompt interventions. Propranolol monotherapy can be an effective and safe first-line treatment strategy for DIHH.

Association of asthma and lung cancer risk: A pool of cohort studies and Mendelian randomization analysis.

BACKGROUND: Over the past 2 decades, population-based studies have shown an increased association between asthma and the risk of lung cancer. However, the causal links between these 2 conditions remain poorly understood. METHODS: We conducted a comprehensive search of various databases, including PubMed, Embase, Web of Science, and Cochrane Library, up until May 04, 2023. Only articles published in English were included in our study. We performed a meta-analysis using random-effects models to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI). Subgroup analyses were conducted based on study design, gender, and histologic types. We also conducted a 2-sample Mendelian randomization (MR) using the genome-wide association study pooled data (408,422 people) published by the UK Biobank to explore further the potential causal relationship between asthma and lung cancer. RESULTS: Our meta-analysis reviewed 24 population-based cohort studies involving 1072,502 patients, revealing that asthma is significantly associated with an increased risk of lung cancer (OR = 1.29, 95% CI 1.19-1.38) in all individuals. Subgroup analysis showed a significantly higher risk of lung cancer in females with asthma (OR = 1.23, 95% CI 1.01-1.49). We found no significant association between asthma and lung adenocarcinoma (LUAD) (OR = 0.76, 95% CI 0.54-1.05), lung squamous carcinomas (LUSC) (OR = 1.09, 95% CI 0.79-1.50), or small-cell lung cancer (SCLC) (OR = 1.00, 95% CI 0.68-1.49). Interestingly, our MR analysis supported an increasing causality between asthma and lung cancer (OR = 1.11, 95% CI 1.04-1.17, P = .0008), specifically in those who ever smoker (OR = 1.09, 95% CI 1.01-1.16, P = .0173) and LUSC pathological type (OR = 1.15, 95% CI 1.05-1.26, P = .0038). CONCLUSION: Through meta-analysis, our study confirms that patients with asthma have a higher risk of developing lung cancer. Our MR study further support an increasing causal relationship between asthma and the risk of lung cancer, particularly in smokers and LUSC. Future studies examining the link between asthma and the risk of developing lung cancer should consider the bias of controlled and uncontrolled asthma.

The Joint Effects of Thunderstorms and Power Outages on Respiratory-Related Emergency Visits and Modifying and Mediating Factors of This Relationship.

BACKGROUND: While limited studies have evaluated the health impacts of thunderstorms and power outages (POs) separately, few have assessed their joint effects. We aimed to investigate the individual and joint effects of both thunderstorms and POs on respiratory diseases, to identify disparities by demographics, and to examine the modifications and mediations by meteorological factors and air pollution. METHODS: Distributed lag nonlinear models were used to examine exposures during three periods (i.e., days with both thunderstorms and POs, thunderstorms only, and POs only) in relation to emergency department visits for respiratory diseases (2005-2018) compared to controls (no thunderstorm/no PO) in New York State (NYS) while controlling for confounders. Interactions between thunderstorms and weather factors or air pollutants on health were assessed. The disparities by demographics and seasons and the mediative effects by particulate matter with aerodynamic diameter ≤2.5µm (PM2.5) and relative humidity (RH) were also evaluated. RESULTS: Thunderstorms and POs were independently associated with total and six subtypes of respiratory diseases in NYS [highest risk ratio (RR) = 1.12; 95% confidence interval (CI): 1.08, 1.17], but the impact was stronger when they co-occurred (highest RR = 1.44; 95% CI: 1.22, 1.70), especially during grass weed, ragweed, and tree pollen seasons. The stronger thunderstorm/PO joint effects were observed on chronic obstructive pulmonary diseases, bronchitis, and asthma (lasted 0-10 d) and were higher among residents who lived in rural areas, were uninsured, were of Hispanic ethnicity, were 6-17 or over 65 years old, and during spring and summer. The number of comorbidities was significantly higher by 0.299-0.782/case. Extreme cold/heat, high RH, PM2.5, and ozone concentrations significantly modified the thunderstorm-health effect on both multiplicative and additive scales. Over 35% of the thunderstorm effects were mediated by PM2.5 and RH. CONCLUSION: Thunderstorms accompanied by POs showed the strongest respiratory effects. There were large disparities in thunderstorm-health associations by demographics. Meteorological factors and air pollution levels modified and mediated the thunderstorm-health effects. https://doi.org/10.1289/EHP13237.

Outcomes of children with clear cell sarcoma of kidney following NWTS strategies in Shanghai China (2003-2021).

BACKGROUND: Although clear cell sarcoma of kidney (CCSK) is rare, it is the second most common renal tumor in children after Wilms' tumor. NWTS and SIOP are two major groups which had made tremendous efforts on renal tumors, but the strategies are different, for NWTS follows the upfront surgery principle providing definite pathology and the SIOP follows the upfront chemotherapy principle, each has its own advantages. Here we aimed to evaluate the outcomes of CCSK in China following NWTS strategies to analyze the prognostic factors. METHODS: For this multicenter retrospective study, a total of 54 patients were enrolled from three children's hospitals, between April 2003 and December 2021. Treatment comprised upfront radical nephrectomy, followed by radiotherapy and intensive chemotherapy. Clinical records were regularly updated. Prognostic factors and survival rates were evaluated. RESULTS: The 54 enrolled patients had a median age of 37 months (range, 4 months to 11.4 years). The stage distribution was 16% stage I (n = 9), 30% stage II (n = 16), 39% stage III (n = 21), and 15% stage IV (n = 8). Among stage IV, metastasis sites included the lung (n = 6), bone (n = 1), and intra-orbital/cervical lymph node (n = 1). After a median follow-up of 5.6 years, the 5-year event-free survival (EFS) was 82.4±5.4%, and overall survival was 88.1±4.6%. The EFS was 100% for stage I, 93.8 ±6.1% for stage II, 71.1±10.0% for stage III, and 68.6±18.6% for stage IV. Univariate analysis revealed that staging (III/IV), tumor rupture, and inferior vena cava tumor thrombus were inferior prognostic factors. Multivariate analysis revealed that tumor rupture was independent poor prognostic factor (P = 0.01, HR 5.9). Among relapsed patients, relapse occurred a median of 11 months after diagnosis (range, 4-41 months), and 50% (4/8) achieved a second complete remission after multiple treatment. None of the six lung metastasis patients received lung RT, only one patient developed a relapse and was salvaged by RT after relapse. CONCLUSIONS: Tumor rupture was independent poor prognostic factor. Upfront surgery of NWTS strategies can make a definite pathology diagnosis, but how to reduce tumor rupture during surgery is important especially in developing countries. The outcomes of patients with stage I-III CCSK in China were comparable to findings in other developed countries. Better outcomes were achieved in stage IV CCSK by using an intensive chemotherapy regimen including carboplatin, which require further confirmation by AREN0321. Lung RT may be safely omitted in selected patients who achieve a compete radiographic response after 6 weeks of systemic treatment (including surgery). Treatment should be encouraged even in CCSK cases with metastasis and relapse.

Subarachnoid hemorrhage misdiagnosed as acute coronary syndrome leading to catastrophic neurologic injury: A case report.

BACKGROUND: Elevated levels of cardiac troponin and abnormal electrocardiogram changes are the primary basis for clinical diagnosis of acute coronary syndrome (ACS). Troponin levels in ACS patients can often be more than 50 times the upper reference limit. Some patients with subarachnoid hemorrhage (SAH) also show electrocardiogram abnormalities, myocardial damage, and elevated cardiac biomarkers. Unlike ACS patients, patients with SAH only have a slight increase in troponin, and the use of anticoagulants or antiplatelet drugs is prohibited. Because of the opposite treatment modalities, it is essential for clinicians to distinguish between SAH and ACS. CASE SUMMARY: A 56-year-old female patient was admitted to the emergency department at night with a sudden onset of severe back pain. The final diagnosis was intraspinal hematoma in the thoracic spine. We performed an emergency thoracic spinal canal hematoma evacuation procedure with the assistance of a microscope. Intraoperatively, diffuse hematoma formation was found in the T7-T10 spinal canal, and no obvious spinal vascular malformation changes were observed. Postoperative head and spinal magnetic resonance imaging (MRI) showed a small amount of SAH in the skull, no obvious abnormalities in the cervical and thoracic spinal canals, and no abnormal signals in the lumbar spinal canal. Thoracoabdominal aorta computed tomography angiography showed no vascular malformation. Postoperative motor system examination showed Medical Research Council Scale grade 1/5 strength in both lower extremities, and the patient experienced decreased sensation below the T12 rib margin and reported a Visual Analog Scale score of 3. CONCLUSION: Extremely elevated troponin levels (more than 50 times the normal range) are not unique to coronary artery disease. SAH can also result in extremely high troponin levels, and antiplatelet drugs are contraindicated in such cases. Emergency MRI can help in the early differential diagnosis, as a misdiagnosis of ACS can lead to catastrophic neurological damage in patients with spontaneous spinal SAH.

Identification of RNMT as an immunotherapeutic and prognostic biomarker: From pan-cancer analysis to lung squamous cell carcinoma validation.

BACKGROUND: Dysregulation of RNA guanine-7 methyltransferase (RNMT) plays a crucial role in the tumor progression and immune responses. However, the detailed role of RNMT in pan-cancer is still unknown. METHODS: Bulk transcriptomic data of pan-cancer were obtained from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases. Single-cell transcriptomic and proteomics data of lung squamous cell carcinoma (LUSC) were analyzed in the Tumor Immune Single-cell Hub 2 (TISCH2) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, respectively. The correlation between RNMT expression and cancer prognosis was analyzed by Cox proportional hazards regression and Kaplan-Meier analyses. The correlation of RNMT expression with common immunoregulators, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and DNA methyltransferase (DNMT) was analyzed. Additionally, the correlation between RNMT expression and immune infiltration level was evaluated. A total of 1287 machine learning combinations were used to construct prognostic models for LUSC. qRT-PCR and Western blot were used to validate the bioinformatics findings of RNMT upregulation in LUSC. RESULTS: RNMT was widely expressed across different cancers, with significant correlation to prognosis in cancers such as kidney chromophobe (KICH) (p = 0.0033, HR = 7.12), liver hepatocellular carcinoma (LIHC) (p = 0.01, HR = 1.41), and others. Notably, RNMT participates in the regulation of the tumor microenvironment. RNMT expression positively correlated with immune cell expression (Spearman's rank correlation, p < 0.05). Moreover, RNMT expression was strongly associated with immunoregulators, TMB, MSI, MMR, and DNMT in most cancer types. Notably, RNMT expression displayed excellent prognostic and immunological performance in LUSC. The expression of RNMT was mainly enriched in B cells of LUSC tissues. qRT-PCR and Western blot verified the high expression of RNMT in LUSC. CONCLUSION: RNMT expression widely correlated with prognosis and immune infiltration in various tumors, especially LUSC. The RNMT detection may provide a new idea for future tumor immune studies and treatment strategies.

Persistent warm-eddy transport to Antarctic ice shelves driven by enhanced summer westerlies.

The offshore ocean heat supplied to the Antarctic continental shelves by warm eddies has the potential to greatly impact the melting rates of ice shelves and subsequent global sea level rise. While featured in modeling and some observational studies, the processes around how these warm eddies form and overcome the dynamic sub-surface barrier of the Antarctic Slope Front over the upper continental slope has not yet been clarified. Here we report on the detailed observations of persistent eddies carrying warm modified Circumpolar Deep Water (CDW) onto the continental shelf of Prydz Bay, East Antarctica, using subsurface mooring and hydrographic section data from 2013-2015. We show the warm-eddy transport is most active when the summer westerlies strengthen, which promotes the upwelling of CDW and initiates eddy formation and intrusions. Our study highlights the important role of warm eddies in the melting of Antarctica's ice shelves, both now and into the future.

Elevated serum uric acid is associated with the risk of advanced staging and vascular involvement in patients with hepatoblastoma: a 14-year retrospective study.

Background: Uric acid is the end product of the purine metabolism pathway, and has been linked to cancer risks and prognosis, but its relationship with hepatoblastoma (HB) remains unclear. This study aims to investigate the association between serum uric acid (SUA) and the advanced tumor staging and unfavorable extra-parenchymal tumor characteristics in patients with HB. Methods: This study enrolled pediatric patients from Xinhua Hospital between 2007 to 2021. A total of 101 participants with newly diagnosed HB were recruited in the study. PRETreatment EXTent of disease (PRETEXT)/PostTreatment Extent of disease (POSTTEXT) staging were evaluated at diagnosis and following neoadjuvant chemotherapy (NAC). Adjusted smoothing spline plots, subgroup analysis and multivariate logistic regression analysis were conducted to estimate the association of different levels of SUA with the advanced tumor staging and present annotation factors. Results: In accordance with SUA tertiles, those patients with higher pretreatment SUA levels showed increased percentages of PRETEXT group IV, vessel involvement and multifocality of tumors. After fully adjustment with the confounding factors, SUA was positively associated with advanced PRETEXT stage IV (OR: 1.72, 95%CI 1.15-2.57, p=0.0080), as well as vascular invasion (OR: 1.29, 95%CI 1.01-1.64, p=0.0396). Compared with the lowest SUA concentration tertile, the highest tertile were independently associated with vessel involvement of tumor in all of the adjusted models. Following NAC, SUA levels were significantly reduced in response to the downstaging of tumors. SUA remained positively associated with advanced POSTTEXT staging and vessel involvement in adjusted models. Patients with highest tertile of posttreatment SUA showed worse 5-year EFS and OS. Conclusion: Elevated SUA were associated with an increased occurrence of advanced PRETEXT/POSTTEXT staging and unfavorable vessel involvement at diagnosis and following NAC in patients with HB. High posttreatment SUA reflected poor tumor responses to NAC. This study linked SUA, a non-invasive laboratory test, with tumor staging and risk prediction for HB.

RT-PCR demonstrates superior sensitivity and specificity in detecting the five neuroblastoma genes compared to the flow cytometry method for measurable residual disease.

Background: Exploring sensitive prognostic methods for patients with relapsed or refractory neuroblastoma (NB) is critical. The five NB genes (NB5) share a common trait: they are highly expressed in NB. Previous studies have identified their expression levels as markers for guiding micrometastasis. This study aimed to explore whether an improved NB5 detection method is superior to flow cytometry for predicting NB metastasis, measurable residual disease (MRD), and prognosis, and whether this result could serve as an independent factor to influence progression-free survival (PFS). Methods: We utilized reverse transcriptase polymerase chain reaction (RT-PCR) to assess the expression of NB5 (CHGA, DCX, DDC, PHOX2B, and TH) in bone marrow (BM), peripheral blood (PB), or cerebrospinal fluid (CSF) samples collected from 71 patients. The correlation between gene expression changes and clinical characteristics, as well as survival rates, based on 113 detections were analyzed. The NB5 detection results' sensitivity and specificity in all 71 patients collected from six research centers with a median follow-up of 14 months were assessed. Results: PB specimens showed 100% concordance with the BM specimens in terms of positive results. Furthermore, the BM specimens exhibited an additional 45.455% (5/11) positive results compared to the 34.091% (30/88) of PB specimens. The BM specimens were positive for NB5 assay, which was significantly higher than the positive results of flow cytometric MRD (15/88, 17.045%). NB5 was mainly expressed in newly diagnosed patients (P=0.043) and positive patients with flow cytometric MRD (P<0.001) or BM morphology (P<0.001). Positive rates of droplet digital PCR (ddPCR) were consistent with those of quantitative RT-PCR (qRT-PCR) in BM (13/18, 72.222%). However, in PB, the positive rate of ddPCR (2/5, 40.000%) was higher than that of qRT-PCR. A total of 38 specimens (BM, PB, CSF) were detected as positive under qRT-PCR. Among the positive results, the analysis revealed a significant difference between the CHGA and TH in pairwise comparisons (P=0.005). PFS analysis showed that among MRD-negative patients, the survival time of the NB5-positive group was significantly lower than that of NB5-negative group (27.408±10.791 vs. 35.961±3.084 months; P=0.034), and in the Cox regression model, risk stratification based on NB5 expression level was an independent prognostic factor for relapsed or refractory disease [95% confidence interval (CI):1.020 to 9.099, hazard ratio (HR) =3.046, P=0.046]. Combining the follow-up results, we found that the sensitivity and specificity of NB5 detection were both 100%. Conclusions: In our study, the improved NB5 detection method showed significantly higher sensitivity in assessing tumor relapse or residual disease compared to flow cytometric MRD. Moreover, it provided a more accurate assessment of treatment efficacy and prognosis. These findings support NB5 detection as an effective method for further stratification and monitoring of patients with relapsed or refractory NB.

A multicenter prospective study on the management of hepatoblastoma in children: a report from the Chinese Children's Cancer Group.

BACKGROUND: This study aimed to identify survival risk factors in Chinese children with hepatoblastoma (HB) and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group (CCCG) in 2016. METHODS: A multicenter, prospective study that included 399 patients with HB from January 2015 to June 2020 was conducted. Patient demographics, treatment protocols, and other related information were collected. Cox regression models and Kaplan-Meier curve methods were used. RESULTS: The 4-year event-free survival (EFS) and overall survival (OS) were 76.9 and 93.5%, respectively. The 4-year EFS rates for the very-low-risk, low-risk, intermediate-risk, and high-risk groups were 100%, 91.6%, 81.7%, and 51.0%, respectively. The 4-year OS was 100%, 97.3%, 94.4%, and 86.8%, respectively. Cox regression analysis found that age, tumor rupture (R +), and extrahepatic tumor extension (E +) were independent prognostic factors. A total of 299 patients had complete remission, and 19 relapsed. Patients with declining alpha-fetoprotein (AFP) > 75% after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those ≤ 75%. CONCLUSIONS: The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 therapy. Age ≥ 8 years, R + , and E + were independent risk factors for prognosis. Patients with a declining AFP > 75% after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.