A Primary Report 166 Cases of Abdominal or Pelvic Neuroblastoma Surgery Utilizing the International Neuroblastoma Surgical Report Form (INSRF).

BACKGROUND AND AIMS: Surgery is pivotal in the management of neuroblastoma (NB), particularly in patients with Image-Defined Risk Factors (IDRFs). The International Neuroblastoma Surgical Report Form (INSRF) was introduced to enhance surgical reporting quality and analyze the defining role of extensive surgery in NB. This study reports our experience with INSRF and explores new criteria for evaluating the extent of surgical resection. METHODS: INSRF was deployed to critically analyze 166 patients with abdominal or pelvic NB who underwent surgery at our department between October 2021 and June 2023. Patient demographics, clinical characteristics, surgical datasets, and postoperative complications were described in detail. Receiver operating characteristic (ROC) curves were used to explore a new method to evaluate the extent of resection. A questionnaire was formulated to obtain attitudes/feedback and commentary from surgical oncologists with INSRF. RESULTS: 166 neuroblastoma patients with a median disease age 36.50 months. This study collated 320 INSRF reports. Among the 166 index cases, 137 were documented by two surgeons, with a concordance rate of 16.78%. Items with high inconsistency were (i) the extent of tumor resection (29.20%), (ii) renal vein involvement (25.55%), (iii) abdominal aorta encasement (16.79%), and (iv) mesenteric infiltration (17.52%). According to INSRF, the extent of resection was complete excision in 86 (51.81%) patients, minimal residual tumor < 5 cm3 in 67 (40.36%) patients, and incomplete excision > 5 cm3 in 13 (7.83%) patients. In ROC curve analysis, the number of vessels encased by tumors > 3 had a high predictive value in determining that a tumor could not be completely resected (AUC 0.916, sensitivity 0.838, specificity 0.826) using INSRF as the gold standard reference. The questionnaires showed that surgeons agreed that the extent of resection and tumor involvement of organ/vascular structures were important, while the definition and intervention(s) of intraoperative complications were less operational and understandable. CONCLUSIONS: INSRF has significant clinical application in neuroblastoma surgery. The extent of resection can be predicted based on the number of tumor-encased blood vessels. Supplementary information should be considered with the INSRF to aid practitioner reporting. Multicenter studies are needed to explore the defining role of INSRF in NB surgical management.

Simultaneous quantification of six proteins related to liver injury using nano liquid chromatography-tandem mass spectrometry.

RATIONALE: In clinical diagnosis of liver injury, which is an important health concern, serum aminotransferase assays have been the go-to method used worldwide. However, the measurement of serum enzyme activity has limitations, including inadequate disease specificity and enzyme specificity. METHODS: With the high selectivity and specificity provided by nano liquid chromatography-tandem mass spectrometry (LC/MS/MS), this work describes a method for the simultaneous determination of six proteins in liver that can be potentially used as biomarkers for liver injury: glutamic-pyruvic transaminase 1 (GPT1), glutamic oxaloacetic transaminase 1 (GOT1), methionine adenosyl transferase 1A (MAT1A), glutathione peroxidase 1 (GPX1), cytokeratin 18 (KRT18) and apolipoprotein E (APOE). RESULTS: In validation, the method was shown to have good selectivity and sensitivity (limits of detection at pg/mL level). The analytical method revealed that, compared with normal mice, in carbon tetrachloride-induced acute liver injury mice, liver MAT1A and GPX1 were significantly lower (p < 0.01 and p < 0.05, respectively), KRT18 was significantly higher (p < 0.05) and APOE and GPT1 were marginally significantly lower (p between 0.05 and 0.1). This is the first work reporting the absolute contents of GPT1, GOT1, MAT1A, GPX1 and KRT18 proteins based on LC/MS. CONCLUSIONS: The proposed method provides a basis for establishing more specific diagnostic indicators of liver injury.

Development of the pediatric family-based dignity therapy protocol for terminally ill children (ages 7-18) and their families: A mixed-methods study.

OBJECTIVES: Dignity therapy (DT) is well-established in adults, and it might potentially benefit the younger population. This study aims to develop a pediatric family-based dignity therapy (P-FBDT) protocol for terminally ill children and their families. METHODS: A parallel mixed-methods design was used. The P-FBDT protocol was developed based on the adult DT, and meanwhile by taking children-specific dignity characteristics and Chinese family-oriented culture into consideration. The protocol was then evaluated and modified based on the quantitative and qualitative feedback from 2-round surveys of 14 pediatric oncology or pediatric palliative care experts. RESULTS: The P-FBDT involves terminally ill children and their families in meaningful interactions including a series of conversations and creative activities, which will be recorded and then edited into a document-based generativity entity. The P-FBDT protocol was recognized as highly reasonable and the P-FBDT interview guide was endorsed as important, acceptable, clear, comprehensive, and suitable to be used in pediatric palliative care practice in Chinese culture (>90%). Potential benefits, possible challenges, and practical considerations of the P-FBDT were also proposed. SIGNIFICANCE OF RESULTS: The P-FBDT was perceived to be potentially beneficial to terminally ill children and their families by engaging in a series of meaningful family interactions and creating a lasting memento to be preserved. The protocol needs to be pilot tested among terminally ill children and families for feasibility and potential efficacy in practice.

Data-Driven Tool for Cross-Run Ion Selection and Peak-Picking in Quantitative Proteomics with Data-Independent Acquisition LC-MS/MS.

Proteomics provides molecular bases of biology and disease, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a platform widely used for bottom-up proteomics. Data-independent acquisition (DIA) improves the run-to-run reproducibility of LC-MS/MS in proteomics research. However, the existing DIA data processing tools sometimes produce large deviations from true values for the peptides and proteins in quantification. Peak-picking error and incorrect ion selection are the two main causes of the deviations. We present a cross-run ion selection and peak-picking (CRISP) tool that utilizes the important advantage of run-to-run consistency of DIA and simultaneously examines the DIA data from the whole set of runs to filter out the interfering signals, instead of only looking at a single run at a time. Eight datasets acquired by mass spectrometers from different vendors with different types of mass analyzers were used to benchmark our CRISP-DIA against other currently available DIA tools. In the benchmark datasets, for analytes with large content variation among samples, CRISP-DIA generally resulted in 20 to 50% relative decrease in error rates compared to other DIA tools, at both the peptide precursor level and the protein level. CRISP-DIA detected differentially expressed proteins more efficiently, with 3.3 to 90.3% increases in the numbers of true positives and 12.3 to 35.3% decreases in the false positive rates, in some cases. In the real biological datasets, CRISP-DIA showed better consistencies of the quantification results. The advantages of assimilating DIA data in multiple runs for quantitative proteomics were demonstrated, which can significantly improve the quantification accuracy.

The dignity of terminally ill children in pediatric palliative care: perspectives of parents and healthcare providers.

BACKGROUND: The Chochinov Dignity Model was developed based on a cohort of adult patients with advanced cancer, but its role among dying children is not clear. This study aims to develop a model of dignity for children receiving pediatric palliative care based on the Chochinov Dignity Model. METHODS: This is a descriptive qualitative study. Participants included a total of 11 parents and 14 healthcare providers who were recruited from a tertiary children's hospital in Beijing and the Pediatric Palliative Care Subspecialty Group of the Pediatrics Society of the Chinese Medical Association using purposive sampling. Thematic framework analysis was used to analyze data. RESULTS: The themes of the empirical Dignity Model were broadly supported in this study, but some themes were interpreted differently in the child population. Compared with the original model, some child-specific themes were identified including acknowledging regret, a sense of security, the company of important loved ones, realizing unfinished wishes, decent and dignified death, resolving family disputes, and fairness. CONCLUSIONS: This is the first study on Dignity Model for terminal children. Knowledge of children's dignity can promote reflection of healthcare providers and caregivers regarding the values underlying their performance in pediatric palliative care, and develop certain practical interventions to strengthen children and their families' sense of dignity at end of life.

A shared decision-making model in pediatric palliative care: a qualitative study of healthcare providers.

BACKGROUND: Pediatric shared decision-making (SDM) is a fundamental part of family-centered care. Pediatric palliative care (PPC) is one of the more difficult fields for healthcare providers when choosing to utilize SDM. However, to our knowledge, there are still few structured approaches of SDM in PPC. We aimed to build a model of SDM in PPC that achieves better care and outcomes for children and their family members. METHODS: This study is a descriptive phenomenology study. Participants included physicians, nurses, and social workers in the PPC team. Participants were individually interviewed face-to-face or via an online meeting software. Data were collected in semi-structured interviews and analyzed using a thematic framework analysis. RESULTS: In total, 27 healthcare providers were interviewed. The model of SDM in PPC identified three themes, including the participants, the principle and the process of SDM. Decision participants involved the children, parents, the PPC team and others. The decision principle had three sub-themes including type, standard and precondition. The decision process describes the fundamental process of SDM and provides suggestions for mobilizing patients and parents to engage in decision-making and seeking conflict resolution. CONCLUSIONS: This is the first study to develop a SDM model in PPC. This model can provide guidance to PPC teams on SDM practices. In addition, the model contributes to the existing body of knowledge by providing a conceptual model for SDM in the context of PPC.

Acquired CFTR dysfunction and dense distribution of ionocytes in nasal mucosa of children with CRS.

BACKGROUND: Ionocytes are rare cells in airway epithelium characterized by a high expression of CFTR. OBJECTIVES: To investigate the morphology and distribution of ionocytes and the function of CFTR in the nasal mucosal epithelium of children. METHODS: The exfoliated cells of nasal mucosa from 101 children were detected using flow cytometry to analyze the number of ionocytes and CFTR and the difference of CFTR function. Nasal mucosa and polyps were collected from 10 children with CRSwNP. The RNAscope of FOXI1 and CFTR was detected in pathological paraffin sections. The expression and distribution of ionocytes and CFTR in nasal mucosa and polyp epithelium were observed. RESULTS: In CRS patients, the number of ionocytes in the nasal epithelium was lower and the number of ionocytes that did not express CFTR was higher, and the function of CFTR was also decreased. The expression of CFTR in the nasal mucosa of CRS showed the characteristics of local dense distribution and increased as the inflammation expanded. The ionocytes were "tadpole-shaped" in the epithelium and gathered in the area of high CFTR expression, the intracellular CFTR was expanded in clusters. Ionocytes that did not express CFTR was more common in the nasal polyps. CONCLUSIONS: The number of ionocytes and the function of CFTR in nasal mucosa of CRS patients decreased. With the expansion of inflammation, CFTR and ionocytes showed more obvious dense distribution. Some ionocytes lost the expression of CFTR and did not show the "tadpole" shape, which may be related to the occurrence of polyps.

Clinicians' practices and attitudes regarding advance care planning in mainland China: A multicenter cross-sectional survey.

OBJECTIVES: This study aims to explore clinicians' practices and attitudes regarding advance care planning (ACP) in mainland China. METHODS: This study was a multicenter cross-sectional survey. Clinicians from tertiary hospitals in Beijing, Guangxi, and Inner Mongolia were invited to participate in the study. A questionnaire was formulated based on related literature to obtain information including demographic characteristics, and practices and attitudes toward ACP. RESULTS: The total number of participants included 285 clinicians. The data response rate was 84.57%. Most of the clinicians had an inadequate understanding of ACP. Only a few clinicians had experience in participating or witnessing an ACP or related end-of-life discussions. Among 285 clinicians, 69.82% of clinicians were willing to introduce ACP to patients. Two hundred and thirty-eight (83.51%) clinicians wanted more education on ACP. Almost all clinicians believed that patients had the right to know about their diagnosis, prognosis, and available care options. Most clinicians (82.11%) regarded that ACP was partially feasible in mainland China. If clinicians had a serious illness, almost everyone was willing to find out their true health status and decide for themselves, and 81.40% wanted to institute an ACP for themselves. The biggest barriers to the use of ACP in mainland China were cultural factors. Statistical analysis revealed that some or good understanding level (P = 0.0052) and practical experience (P = 0.0127) of ACP were associated with the positive willingness. SIGNIFICANCE OF RESULTS: ACP is still in its infancy in mainland China. Clinicians had inadequate understanding and minimal exposure to ACP. Most clinicians recognized the value and significance of ACP and had a positive attitude toward ACP. Clinicians need to be provided with education and training to promote their ACP practices. Culturally appropriate ACP processes and documents need to be developed based on Chinese culture and Chinese needs.

Accuracy of equations for predicting 24-h urinary potassium excretion from spot urine samples in Chinese children.

Accurate assessments of potassium intake in children are important for the early prevention of CVD. Currently, there is no simple approach for accurate estimation of potassium intake in children. We aim to evaluate the accuracy of 24-h urinary potassium excretion (24UKV) estimation in children using three common equations: the Kawasaki, Tanaka and Mage formulas, in a hospital-based setting. A total of 151 participants aged 5-18 years were initially enrolled, and spot urine samples were collected in the whole 24-h duration to measure the concentrations of potassium and creatinine. We calculated the mean difference, absolute and relative difference and misclassification rate between measured 24UKV and the predicted ones using Kawasaki, Tanaka and Mage formulas in 129 participants. The mean measured 24UKV was 1193·3 mg/d in our study. Mean differences between estimated and measured 24UKV were 1215·6, -14·9 and 230·3 mg/d by the Kawasaki, Tanaka and Mage formulas, respectively. All estimated 24UKV were significantly different from the measured values in all the time point (all P < 0·05), except for the predicted values from Tanaka formula using morning, afternoon and evening spot urine. The proportions with relative differences over 40 % were 87·2%, 32·5% and 47·3 % for Kawasaki, Tanaka and Mage formulas, respectively. Misclassification rates were 91·5 % for Kawasaki, 44·4 % for Tanaka and 58·9 % for Mage formula at the individual level. Our findings showed that misclassification could occur on the individual level when using Kawasaki, Tanaka and Mage formulas to estimate 24UKV from spot urine in the child population.

Assessment of evidence on reported non-genetic risk factors of congenital heart defects: the updated umbrella review.

BACKGROUND: Congenital heart defect (CHD) is the leading cause of birth defects globally, which results in a great disease burden. It is still imperative to detect the risk factors of CHD. This umbrella review aimed to comprehensively summarize the evidence and grade the evidence of the associations between non-genetic risk factors and CHD. METHODS: Databases including Medline, Embase, Web of Science, Cochrane Library, and four Chinese databases were searched from inception to 18 Jan 2022. The reference lists of systematic reviews (SR) and meta-analyses (MA) were screened, which aimed to explore the non-genetic risk factors of CHD. Subsequently, titles and abstracts of identified records and full texts of selected SR/MA were screened by two independent reviewers based on predefined eligibility criteria. A priori developed extraction form was used to abstract relative data following the PRISMA 2020 and MOOSE guidelines. The risk of bias was assessed with the AMSTAR2 instrument. Data were synthesized using fixed-effects and random-effects meta-analyses, respectively. Finally, the evidence on the association of non-genetic risk factors and CHD was graded using Ioannidis's five-class evidence grade. RESULTS: A total of 56 SRs, encompassing 369 MAs, were identified. The risk factors included relative factors on air pollution, reproductive-related factors, parental age and BMI, parental life habits, working and dwelling environment, maternal drug exposure, and maternal disease. Based on AMSTAR2 criteria, only 16% (9/56) of SRs were classified as "Moderate". One hundred and two traceable positive association MAs involving 949 component individual studies were included in further analysis and grading of evidence. Family genetic history, number of abortions, maternal obesity, especially moderate or severe obesity, decoration materials, harmful chemicals, noise during pregnancy, folic acid supplementation, SSRIs, SNRIs, any antidepressants in the first trimester, maternal DM (including both PGDM and GDM), and gestational hypertension were convincing and highly suggestive factors for CHD. After sensitivity analyses based on cohort studies, some grades of evidence changed. CONCLUSION: The present umbrella review will provide evidence-based information for women of childbearing age before or during pregnancy to prevent CHD. In addition, sensitivity analysis based on cohort studies showed the changed evidence levels. Therefore, future SR/MA should concern the sensitivity analysis based on prospective birth cohort studies and case-control studies.

The development and initial evaluation of referral flowchart for suspected neuroblastoma for pediatricians in nononcology clinics in China.

BACKGROUND: The delayed diagnosis of neuroblastoma (NB) is common in China, which results in the prognosis of NB in China lagging behind that in developed countries. METHODS: A referral flowchart for suspected NB was implemented in nononcology clinics at Beijing Children's Hospital (BCH). Patients with symptoms of suspected NB were referred from nononcology clinics in BCH to oncology clinics and confirmed NB cases were regarded as referral group. The control group comprised patients initially diagnosed with NB who came directly to oncology clinics in BCH from other regions nationwide. The age at NB diagnosis was compared as primary outcome, and the 5-year overall survival (OS) and event-free survival (EFS) were compared via the Kaplan-Meier method and log-rank tests. RESULTS: In total, 3337 children with suspected NB were screened consecutively from 687 070 pediatric patients. Through examination of urine vanillylmandelic acid and homovanillic acid, or B-ultrasound, 102 of 3337 patients were referred to oncologists for comprehensive evaluations. Eventually, 29 referred patients were diagnosed as NB and the hospital-based diagnosis rate of NB was 4.2 per 100 000 visits. The median age at diagnosis in the referral group was 21.0 months, which was 9 months earlier than that of the control group (30.0 months, P = .026). The 5-year OS rate was 72.4% in the referral group, which was higher than that of the control group (66.7%) but without statistical significance (P = .664). CONCLUSION: Delayed NB detection could be avoided by training pediatricians in nononcology clinics to detect suspected NB and refer these patients to oncologists.

Anastomotic stricture indexes for endoscopic balloon dilation after esophageal atresia repair: a single-center study.

We investigated changes in anastomotic stricture indexes (SIs) and stricture diameter (SD) between before and 6 months after the first dilatation in children with anastomotic stricture after esophageal atresia (EA) repair and identified predictors of medium-term dilatation success (success for at least 3 months). We retrospectively reviewed the records and measurement indexes of patients who underwent post-EA repair endoscopic balloon dilatation between November 2017 and August 2019 in our hospital. We identified diagnostic and performance indicators that predicted medium-term dilatation success by univariate and multivariate analyses and receiver operator characteristic (ROC) curve analysis. Sixty patients (34 boys and 26 girls) showed post-EA repair anastomotic stricture. Paired sample t-tests showed that SD (P < 0.001), upper pouch SI (U-SI, P < 0.001), lower pouch SI (L-SI, P < 0.001), upper pouch esophageal anastomotic SI (U-EASI, P < 0.001) and lower pouch EASI (L-EASI, P < 0.001) were significantly better at 6 months after than before the first dilatation. Logistic regression analysis showed that dilatation number (P = 0.002) and U-SI at 6 months after the first dilatation (P = 0.019) significantly predicted medium-term dilatation success. ROC curve analysis revealed that combining U-SI (cut-off value = 55.6%) and dilatation number (cut-off value = 10) had good accuracy in predicting medium-term dilatation success 6 months after the first dilatation (area under the curve-ROC: 0.95). In conclusion, endoscopic balloon dilatation significantly improved SD and SIs in children with post-EA repair anastomotic stricture. Dilatation number and U-SI at 6 months after the first dilatation were useful in predicting medium-term dilatation success and could represent a supplementary method to improve judgment regarding whether further dilatation is needed 6 months after the first dilatation.

Clinical characteristics and risk factors of 47 cases with ruptured neuroblastoma in children.

BACKGROUND: Neuroblastoma (NB) tumor rupture is a rare oncology emergency with a poor prognosis. We aimed to evaluate patient clinical characteristics and risk factors for ruptured NB. METHODS: A retrospective study of 47 patients with confirmed NB rupture between January 2009 and January 2019 at Beijing Children's Hospital was conducted. To identify tumor rupture risk factors in high-risk NB patients, we included 93 consecutive non-ruptured high-risk NB patients from January 2017 to January 2019. RESULTS: The median age at presentation was 29 months (adrenal and retroperitoneum origin) for 47 ruptured NB patients. Spontaneous tumor rupture occurred in 22 cases; 18 cases occurred during or after the first chemotherapy cycle, and 7 occurred after core needle biopsy. Five patients died of tumor rupture, and 17 patients' parents refused further antitumor therapy. Among the 25 remaining patients, 6 survived without disease, 5 received ongoing treatment and achieved stable disease, and 14 died. According to multivariate logistic regression analysis, a maximum primary tumor diameter > 13.20 cm and MYCN gene amplification were independent risk factors for tumor rupture within high-risk NB. CONCLUSIONS: Tumor rupture is an uncommon, life-threatening event for NB patients; these patients are most likely to have poor outcomes due to tumor recurrence or rapid progression. Several treatment modalities, including symptomatic support therapy and chemotherapy, are important for saving lives and for developing NB risk-based treatment in the future.

Spiritual needs and communicating about death in nonreligious theistic families in pediatric palliative care: A qualitative study.

BACKGROUND: Spiritual support should be offered to all patients and their families regardless of their affiliated status with an organized religion. AIM: To understand nonreligious theistic parents' spirituality and to explore how parents discuss death with their terminally ill children in mainland China. DESIGN: Qualitative study. SETTING/PARTICIPANTS: This study was conducted in the hematology oncology center at Beijing Children's Hospital. Participants in this study included 16 bereaved parents. RESULTS: Participants described themselves as nonreligious but showed a tendency toward a particular religion. Parents sought religious support in the face of the life-threatening conditions that affected their child and regarded the religious belief as an important way to get psychological and spiritual comfort after experiencing the death of their child. Religious support could partially address parents' spiritual needs. Parents' spiritual needs still require other supports such as bereavement services, death education, and family support groups. Some parents stated that it was difficult to find a way to discuss death with their children. For patients who come from nonreligious theistic families, their understanding of death was more complex and may be related to atheism. CONCLUSION: Religious support could be an element of spiritual support for nonreligious theistic parents of terminally ill children. Multiple strategies including religious supports and nonreligious supports should be rationally integrated into spiritual support of nonreligious theistic family. Patient's personal belief in death should be assessed before discussing death with them.

Combination of gamma-glutamyl transferase and liver stiffness measurement for biliary atresia screening at different ages: a retrospective analysis of 282 infants.

BACKGROUND: This study aims to explore the diagnostic accuracy of the combination of gamma-glutamyl transferase (GGT) and liver stiffness measurement (LSM) for biliary atresia (BA) screening at different ages. METHODS: Our retrospective study involved 282 infants under the age of 120 days with jaundice who were admitted into Beijing Children's Hospital between January 2016 to December 2018. The GGT and LSM levels of infants were obtained. A parallel test was used, and ROC curve was created to obtain cutoff values of GGT and LSM for BA infants at different ages. RESULTS: Of the 282 infants, 135 were diagnosed with BA and 147 were non-BA infants. In all age groups (A: ≤60 days; B: 61-90 days; C: 91-120 days), the LSM and GGT levels of the BA group were significantly higher than that of the non-BA group, P < 0.05. The cutoff value of GGT and LSM to diagnosis BA was 191.2 U/L, 213.2 U/L, 281.5 U/L and 7.5 kPa, 10.0 kPa, 11.0 kPa in groups A, B and C, respectively. The parallel test was used to determine a sensitivity of 97.3, 98.1 and 100% in group A, B and C when either GGT or LSM levels were met in BA infants. The sensitivities of parallel testing for group A and B were higher than LSM or GGT used alone. CONCLUSIONS: Cutoff values of GGT and LSM to screen BA increased with age. Parallel testing of GGT and LSM in infants who are younger than 90 days old can decrease the rate of BA misdiagnosis.

Clinical and Prognostic Characteristics of 53 Cases of Extracranial Malignant Rhabdoid Tumor in Children. A Single-Institute Experience from 2007 to 2017.

BACKGROUND: The aim of this study is to add to the current knowledge regarding extracranial malignant rhabdoid tumor (MRT), a rare and highly aggressive tumor that occurs most commonly in infants and young children. PATIENTS AND METHODS: A retrospective medical record review was conducted on 53 patients with pathologically confirmed MRT in Beijing Children's Hospital between January 2007 and October 2017. RESULTS: Fifty-three patients were diagnosed with MRT at a median age of 16 months, including 32 cases of malignant rhabdoid tumor of the kidney (MRTK) and 21 cases of extrarenal extracranial rhabdoid tumor (EERT). Fourteen (14/32, 43.75%) patients with MRTK and five (5/21, 23.81%) patients with EERT had metastases at diagnosis, and quite a few number of cases occurred tumor rupture (26.42%). Among the 53 patients, 40 (75.47%) patients died, 10 (18.87%) patients survived, and 3 patients (5.66%) were lost to follow-up. Among the 40 dead patients, 38 patients died from rapid progression of the disease or tumor recurrence, and 2 patients died of severe postoperative complications. Most of the recurrent or relapsed cases (94.11%) occurred within 8 months, with a median time of 76 days after diagnosis. The overall survival rates of 3 years and 5 years for the entire cohort were 23.71% and 18.44%, respectively. After survival analysis, it was clear that a younger age at diagnosis and distant stage patients had relatively poor outcomes. The effect of treatment was the most difficult to analyze because patients were not treated uniformly. Statistically significant differences in survival were noted among patients treated with standard chemotherapy, total resection, and radiotherapy. CONCLUSION: Extracranial MRT is still a highly aggressive tumor in children. Younger patients and those suffering from metastatic disease were most likely to have a poor outcome because of rapid progression or recurrence of the tumor. IMPLICATIONS FOR PRACTICE: This is the largest single-institutional report that investigates the clinical characteristics and outcomes of extracranial malignant rhabdoid tumor (MRT) in China. Our study showed that gross hematuria and tumor rupture were typical characteristics of malignant rhabdoid tumor of the kidney. After survival analysis, it was found that the advanced stage of the tumor and an age ≤12 months at diagnosis were significantly associated with poorer survival. Although extracranial MRT is still a highly aggressive tumor in children, multimodal treatment approach, including chemotherapy, surgery, and radiotherapy, should be employed for this disease.

Can statistic adjustment of OR minimize the potential confounding bias for meta-analysis of case-control study? A secondary data analysis.

BACKGROUND: Different confounder adjustment strategies were used to estimate odds ratios (ORs) in case-control study, i.e. how many confounders original studies adjusted and what the variables are. This secondary data analysis is aimed to detect whether there are potential biases caused by difference of confounding factor adjustment strategies in case-control study, and whether such bias would impact the summary effect size of meta-analysis. METHODS: We included all meta-analyses that focused on the association between breast cancer and passive smoking among non-smoking women, as well as each original case-control studies included in these meta-analyses. The relative deviations (RDs) of each original study were calculated to detect how magnitude the adjustment would impact the estimation of ORs, compared with crude ORs. At the same time, a scatter diagram was sketched to describe the distribution of adjusted ORs with different number of adjusted confounders. RESULTS: Substantial inconsistency existed in meta-analysis of case-control studies, which would influence the precision of the summary effect size. First, mixed unadjusted and adjusted ORs were used to combine individual OR in majority of meta-analysis. Second, original studies with different adjustment strategies of confounders were combined, i.e. the number of adjusted confounders and different factors being adjusted in each original study. Third, adjustment did not make the effect size of original studies trend to constringency, which suggested that model fitting might have failed to correct the systematic error caused by confounding. CONCLUSIONS: The heterogeneity of confounder adjustment strategies in case-control studies may lead to further bias for summary effect size in meta-analyses, especially for weak or medium associations so that the direction of causal inference would be even reversed. Therefore, further methodological researches are needed, referring to the assessment of confounder adjustment strategies, as well as how to take this kind of bias into consideration when drawing conclusion based on summary estimation of meta-analyses.

A pair of DICER1-positive monozygotic twins: One with pleuropulmonary blastoma, another with acute transient hepatitis.

Pleuropulmonary blastoma (PPB) is the most common primary malignant neoplasm of the lung in children that is associated with a germline mutation in DICER1. In this report, we share an interesting case of a pair of monozygotic twins: one of them developed PPB when she was 4-year old, while the other developed acute transient hepatitis when she was 5-year old. Next-Gen sequencing for DICER1 mutations of their family revealed that both twins and their mother had c.C3675A mutation. The mother also had a history of multinodular goiter. Identification of DICER1 mutation carriers and close surveillance of individuals at risk for DICER1 syndrome may allow early detection and hence better outcome.

Multimorbidity and Genetic Characteristics of DICER1 Syndrome Based on Systematic Review.

It has been reported that germline DICER1 mutations correlate with a distinctive human disease syndrome. Many published studies within this field have been conducted based on rare cases. We systematically searched bibliographic databases, including PubMed, Embase, and COSMIC for articles which are related to diseases covered by DICER1 syndrome. The weighted summary of mutation frequencies among patients with pleuropulmonary blastoma (PPB), cystic nephroma (CN), and Sertoli-Leydig cell tumor (SLCT) were calculated. Forty-nine eligible articles were included. In total, 72 cases with multimorbidity of DICER1 syndrome were identified. More females (n=46, 64%) presented with multimorbidity than males (n=18, 25%) and the remaining 8 patients' sex were unknown. Nineteen of 72 patients with multimorbidity suffered from another disease that was not yet included in DICER1 syndrome, which would provide potential phenotypes of DICER1 syndrome. The germline DICER1 mutation frequencies in PPB, CN, and SLCT were 66.9%, 73.2%, and 57.1%, respectively. The somatic DICER1 mutation frequencies of PPB, CN, and SLCT were 92.4%, 87.9%, and 43.3%, respectively. Majority of patients with multimorbidity of DICER1 syndrome were mutation positive individuals so that multimorbidity may suggest the possible germline mutation of these patients and their relatives.