Disrupted individual-level morphological brain network in spinal muscular atrophy types 2 and 3.

BACKGROUND AND OBJECTIVE: Spinal muscular atrophy (SMA) is one of the most common monogenic neuromuscular diseases, and the pathogenesis mechanisms, especially the brain network topological properties, remain unknown. This study aimed to use individual-level morphological brain network analysis to explore the brain neural network mechanisms in SMA. METHODS: Individual-level gray matter (GM) networks were constructed by estimating the interregional similarity of GM volume distribution using both Kullback-Leibler divergence-based similarity (KLDs) and Jesen-Shannon divergence-based similarity (JSDs) measurements based on Automated Anatomical Labeling 116 and Hammersmith 83 atlases for 38 individuals with SMA types 2 and 3 and 38 age- and sex-matched healthy controls (HCs). The topological properties were analyzed by the graph theory approach and compared between groups by a nonparametric permutation test. Additionally, correlation analysis was used to assess the associations between altered topological metrics and clinical characteristics. RESULTS: Compared with HCs, although global network topology remained preserved in individuals with SMA, brain regions with altered nodal properties mainly involved the right olfactory gyrus, right insula, bilateral parahippocampal gyrus, right amygdala, right thalamus, left superior temporal gyrus, left cerebellar lobule IV-V, bilateral cerebellar lobule VI, right cerebellar lobule VII, and vermis VII and IX. Further correlation analysis showed that the nodal degree of the right cerebellar lobule VII was positively correlated with the disease duration, and the right amygdala was negatively correlated with the Hammersmith Functional Motor Scale Expanded (HFMSE) scores. CONCLUSIONS: Our findings demonstrated that topological reorganization may prioritize global properties over nodal properties, and disrupted topological properties in the cortical-limbic-cerebellum circuit in SMA may help to further understand the network pathogenesis underlying SMA.

Cardiac function evaluation in children with spinal muscular atrophy: A case-control study.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by degeneration of lower motor neurons, resulting in progressive muscle weakness and atrophy. However, little is known regarding the cardiac function of children with SMA. METHODS: We recruited SMA patients younger than 18 years of age from January 1, 2022, to April 1, 2022, in the First Affiliated Hospital of Sun Yat-sen University. All patients underwent a comprehensive cardiac evaluation before treatment, including history taking, physical examination, blood tests of cardiac biomarkers, assessment of echocardiography and electrocardiogram. Age/gender-matched healthy volunteers were recruited as controls. RESULTS: A total of 36 SMA patients (26 with SMA type 2 and 10 with SMA type 3) and 40 controls were enrolled in the study. No patient was clinically diagnosed with heart failure. Blood tests showed elevated values of creatine kinase isoenzyme M and isoenzyme B (CK-MB) mass and high-sensitivity cardiac troponin T (hs-cTnT) in spinal muscular atrophy (SMA) patients. Regarding echocardiographic parameters, SMA children were detected with lower global left and right ventricular longitudinal strain, abnormal diastolic filling velocities of trans-mitral and trans-tricuspid flow. The results revealed no clinical heart dysfunction in SMA patients, but subclinical ventricular dysfunction was seen in SMA children including the diastolic function and myocardial performance. Some patients presented with elevated heart rate and abnormal echogenicity of aortic valve or wall. Among these SMA patients, seven patients (19.4%) had scoliosis. The Cobb's angles showed a significant negative correlation with LVEDd/BSA, but no correlation with other parameters, suggesting that mild scoliosis did not lead to significant cardiac dysfunction. CONCLUSIONS: Our findings warrant increased attention to the cardiac status and highlight the need to investigate cardiac interventions in SMA children.

Association between multiple-heavy-metal exposures and systemic immune inflammation in a middle-aged and elderly Chinese general population.

BACKGROUND: Exposure to heavy metals alone or in combination can promote systemic inflammation. The aim of this study was to investigate potential associations between multiple plasma heavy metals and markers of systemic immune inflammation. METHODS: Using a cross-sectional study, routine blood tests were performed on 3355 participants in Guangxi, China. Eight heavy metal elements in plasma were determined by inductively coupled plasma mass spectrometry. Immunoinflammatory markers were calculated based on peripheral blood WBC and its subtype counts. A generalised linear regression model was used to analyse the association of each metal with the immunoinflammatory markers, and the association of the metal mixtures with the immunoinflammatory markers was further assessed using weighted quantile sum (WQS) regression. RESULTS: In the single-metal model, plasma metal Fe (log10) was significantly negatively correlated with the levels of immune-inflammatory markers SII, NLR and PLR, and plasma metal Cu (log10) was significantly positively correlated with the levels of immune-inflammatory markers SII and PLR. In addition, plasma metal Mn (log10 conversion) was positively correlated with the levels of immune inflammatory markers NLR and PLR. The above associations remained after multiple corrections. In the mixed-metal model, after WQS regression analysis, plasma metal Cu was found to have the greatest weight in the positive effects of metal mixtures on SII and PLR, while plasma metals Mn and Fe had the greatest weight in the positive effects of metal mixtures on NLR and LMR, respectively. In addition, blood Fe had the greatest weight in the negative effects of the metal mixtures for SII, PLR and NLR. CONCLUSION: Plasma metals Cu and Mn were positively correlated with immunoinflammatory markers SII, NLR and PLR. While plasma metal Fe was negatively correlated with immunoinflammatory markers SII, NLR, and PLR.

Single walled carbon nanotubes band gap width measurement and the influence of nitrogen doping research.

The adjustment and measurement of the band gap width of single-walled carbon nanotubes are crucial for optimizing the design and enhancing the performance of carbon-based devices. This study utilizes the relationship between the band gap and temperature of semiconductor-based carbon nanotubes. The electrical conductivity of carbon nanotubes was obtained at various temperatures, and the corresponding band gap width (0.57 eV) was determined. The introduction of nitrogen results in a reduction of the band gap width and an increase in current flow between the device source and drain electrodes. Theoretical calculation demonstrated that nitrogen doping not only increases the conductivity of carbon nanotubes but also effectively inhibits the Schottky barrier between carbon nanotubes and metal electrodes. The Schottky barrier and the internal electric field can be effectively modulated via nitrogen doping in carbon nanotubes, which enhances the performance of carbon-based devices.

Gray and white matter abnormalities in children with type 2 and 3 SMA: A morphological assessment.

This study investigated the changes in brain gray and white matter structure in SMA patients and their correlation with the severity of the disease. A total of 43 SMA patients (including 22 type II and 21 type III SMA patients) and 37 healthy controls were evaluated by MRI. The gray matter volume, gray matter thickness, gray matter surface area, and white matter volume of designated brain regions automatically segmented by FreeSurfer, were compared. We evaluate clinical characteristics of SMA and study the correlation between clinical characteristics and structural changes. SMA showed significant bilateral cortical superficial area loss in the frontal, parietal, and temporal lobes and global white matter volume decreases. Moreover, these patients were also found with an increased mean thickness of entire brain and right gray matter. An increased right postcentral gyrus superficial area, right central sulcus volume, and white matter volume of the right postcentral were associated with higher HFMSE scores. CONCLUSION: Type 2 and 3 children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. The lack of SMN protein possibly interacted with cerebellar structural changes in somatosensory areas. WHAT IS KNOWN: • MRI has found brain changes in SMA patients, however, there is no unified conclusion and lack of correlation with clinical degree in children SMA with type 2-3. WHAT IS NEW: • Type II and II children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. Cerebellar structural changes in somatosensory areas may attribute to the lack of SMN protein.

Theoretical and experimental investigations of enhanced carbon nanotube-gold interface conductivity through nitrogen doping.

It is necessary to establish high-quality contact between carbon nanotubes and metals in carbon-based devices. However, how to control and reduce contact resistance still remains unsolved. In this study, the effect of N doping in single-walled carbon nanotubes on the contact resistance with gold was studied by combining theoretical calculation with experimental methods. The theoretical results indicate that nitrogen doping in carbon nanotubes can control the bottom of the carbon nanotube conduction band downward, the Fermi level enters the conduction band, the height of the Schottky barrier between the bottom of the carbon nanotube conduction band and the gold Fermi level decreases, and the increase in doping concentration leads to the decrease of Schottky barrier width. As a result, the conductivity between the gold and carbon nanotube interface is enhanced. During experiments, the carrier density and the current of the gold and carbon nanotube device increase gradually with the increase in N doping concentration and a good electron transport channel is established between the gold and carbon nanotubes. The high-quality contact is crucial to reducing the size, improving the performance, and reducing the power consumption of carbon-based devices.

Association Between Combined Polymetallic Exposure and Osteoporosis.

Combined polymetallic exposure may be an influential factor in osteoporosis. This study aimed to explore the association between polymetallic combined exposure and osteoporosis. A total of 2115 participants were included. Plasma concentrations of 22 metals were determined by inductively coupled plasma mass spectrometry. Osteoporosis was defined as a T ≤ - 2.5. The least absolute shrinkage and selection operator (LASSO) regression, binary logistics regression, and Bayesian kernel machine regression (BKMR) model were used to explore the association between plasma metals and osteoporosis. LASSO regression showed that 10 metals were associated with osteoporosis in the total population (magnesium, calcium, manganese, nickel, cobalt, arsenic, selenium, rubidium, cadmium, aluminum) and women (magnesium, calcium, molybdenum, nickel, cobalt, arsenic, selenium, rubidium, cadmium, aluminum), and four metals associated with men (magnesium, cobalt, aluminum, iron). Logistics regression showed that in total population, magnesium (ORQ3 = 0.653, 95% CI = 0.446-0.954) was negatively correlated with osteoporosis, while aluminum (ORQ2 = 1.569, 95% CI = 1.095-2.248, ORQ4 = 1.616, 95% CI = 1.109-2.354) and cadmium (ORQ4 = 1.989, 95% CI = 1.379-2.870) were positively correlated; in women, magnesium (ORQ3 = 0.579, 95% CI = 0.379-0.883) was negatively correlated with osteoporosis, while aluminum (ORQ2 = 1.563, 95% CI = 1.051-2.326, ORQ4 = 1.543, 95% CI = 1.024-2.326) and cadmium (ORQ3 = 1.482, 95% CI = 1.003-2.191, ORQ4 = 1.740, 95% CI = 1.167-2.596) were positively correlated. BKMR model showed that combined polymetallic exposure had an overall positive effect on osteoporosis, magnesium was negatively associated with osteoporosis, and cadmium, selenium, and aluminum were positively associated with osteoporosis. Metal mixtures in plasma were associated with osteoporosis risk. Magnesium may reduce the risk of osteoporosis, while cadmium, selenium, and aluminum may increase the risk of osteoporosis. Future studies needed to explore correlations and mechanisms.

An atlas of genetic scores to predict multi-omic traits.

The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics1. Here we examine a large cohort (the INTERVAL study2; n = 50,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n = 3,175; Olink, n = 4,822), plasma metabolomics (Metabolon HD4, n = 8,153), serum metabolomics (Nightingale, n = 37,359) and whole-blood Illumina RNA sequencing (n = 4,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank3 to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores.

Metagenomic next-generation sequencing for the diagnosis of Pneumocystis jirovecii Pneumonia in critically pediatric patients.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of metagenomic next-generation sequencing (mNGS) for the diagnosis of Pneumocystis jirovecii Pneumonia (PCP) in critically pediatric patients. METHODS: Seventeen critically pediatric patients with PCP and sixty patients diagnosed with non-PCP pneumonia who were admitted in pediatric intensive care unit between June 2018 and July 2021 were enrolled. Conventional methods and mNGS for detecting Pneumocystis jirovecii (P. jirovecii) were compared. The patients' demographics, comorbidities, laboratory test results, antibiotic treatment response and 30 day mortality were analyzed. RESULT: The mNGS showed a satisfying diagnostic performance with a sensitivity of 100% in detecting P. jirovecii compared with Gomori methenamine silver staining (5.9%), serum (1,3)-ß-D-glucan (86.7%) and and LDH (55.6%). The diagnostic specificity of mNGS for PCP was higher than that of serum BDG (56.7%) and LDH (71.4%). In PCP group, over one thirds' cases had mixed infections. Compared with survivors, non-survivors had higher stringently mapped read numbers (SMRNs) in bronchoalveolar lavage fluid (BALF) sample (P < 0.05), suggesting SMRNs were closely associated with the severity of response. The detection for P. jirovecii by mNGS both in BALF and blood samples reached a concordance rate of 100%, and the SMRNs in the BALF were remarkably higher than that in blood samples. Initial antimicrobial treatment was modified in 88.2% of PCP patients based on the mNGS results. CONCLUSION: The mNGS is a potential and efficient technology in diagnosing PCP and shows a satisfying performance in the detection of co-pathogens. Both blood and BALF samples for mNGS are suggested for the presumptive diagnosis of PCP.

Proteomic Predictors of Incident Diabetes: Results From the Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: The plasma proteome preceding diabetes can improve our understanding of diabetes pathogenesis. RESEARCH DESIGN AND METHODS: In 8,923 Atherosclerosis Risk in Communities (ARIC) Study participants (aged 47-70 years, 57% women, 19% Black), we conducted discovery and internal validation for associations of 4,955 plasma proteins with incident diabetes. We externally validated results in the Singapore Multi-Ethnic Cohort (MEC) nested case-control (624 case subjects, 1,214 control subjects). We used Cox regression to discover and validate protein associations and risk-prediction models (elastic net regression with cardiometabolic risk factors and proteins) for incident diabetes. We conducted a pathway analysis and examined causality using genetic instruments. RESULTS: There were 2,147 new diabetes cases over a median of 19 years. In the discovery sample (n = 6,010), 140 proteins were associated with incident diabetes after adjustment for 11 risk factors (P < 10-5). Internal validation (n = 2,913) showed 64 of the 140 proteins remained significant (P < 0.05/140). Of the 63 available proteins, 47 (75%) were validated in MEC. Novel associations with diabetes were found for 22 the 47 proteins. Prediction models (27 proteins selected by elastic net) developed in discovery had a C statistic of 0.731 in internal validation, with ΔC statistic of 0.011 (P = 0.04) beyond 13 risk factors, including fasting glucose and HbA1c. Inflammation and lipid metabolism pathways were overrepresented among the diabetes-associated proteins. Genetic instrument analyses suggested plasma SHBG, ATP1B2, and GSTA1 play causal roles in diabetes risk. CONCLUSIONS: We identified 47 plasma proteins predictive of incident diabetes, established causal effects for 3 proteins, and identified diabetes-associated inflammation and lipid pathways with potential implications for diagnosis and therapy.

Association of CYP19A1 Gene, Plasma Zinc, and Urinary Zinc with the Risk of Type 2 Diabetes Mellitus in a Chinese Population.

To explore the effects of CYP19A1 gene polymorphisms, plasma zinc, and urinary zinc levels and their interactions on type 2 diabetes mellitus (T2DM) in residents of Gongcheng County, Guangxi, China. The case-control study was used for the investing. The MassARRAY System was applied to genotype the CYP19A1 genes rs752760, rs10046, rs10459592, and rs700518 in 540 study subjects. Plasma and urinary zinc concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Conditional logistic regression showed that rs752760 and plasma zinc were associated with T2DM risks with ORs of 0.593 (95% CI: 0.371-0.948) and 0.563 (95% CI: 0.356-0.889), respectively. Unconditional logistic regression analysis showed an association between urinary zinc levels and the risk of T2DM as well, with an OR of 0.352 (95% CI: 0.212-0.585). The results of the multiplicative interaction model showed that the rs752760 T allele was associated with a significantly reduced risk of T2DM with moderate/low plasma zinc levels, with ORs of 0.340 (95% CI: 0.161-0.715) and 0.583 (95% CI: 0.346-0.981), respectively, and the rs752760 T allele was also associated with a significantly decreased risk of T2DM with moderate/low urinary zinc levels, with ORs of 0.358 (95% CI: 0.201-0.635) and 0.321 (95% CI: 0.183-0.562), respectively. CYP19A1 rs752760 T allele and moderate/low plasma/urinary zinc levels reduce the risk of T2DM.

Rapid and precise diagnosis of pneumonia coinfected by Pneumocystis jirovecii and Aspergillus fumigatus assisted by next-generation sequencing in a patient with systemic lupus erythematosus: a case report.

BACKGROUND: Pneumocystis jirovecii and Aspergillus fumigatus, are opportunistic pathogenic fungus that has a major impact on mortality in patients with systemic lupus erythematosus. With the potential to invade multiple organs, early and accurate diagnosis is essential to the survival of SLE patients, establishing an early diagnosis of the infection, especially coinfection by Pneumocystis jirovecii and Aspergillus fumigatus, still remains a great challenge. CASE PRESENTATION: In this case, we reported that the application of next -generation sequencing in diagnosing Pneumocystis jirovecii and Aspergillus fumigatus coinfection in a Chinese girl with systemic lupus erythematosus (SLE). Voriconazole was used to treat pulmonary aspergillosis, besides sulfamethoxazole and trimethoprim (SMZ-TMP), and caspofungin acetate to treat Pneumocystis jirovecii infection for 6 days. On Day 10 of admission, her chest radiograph displayed obvious absorption of bilateral lung inflammation though the circumstance of repeated fever had not improved. Unfortunately, the patient discharged from the hospital since the financial burden, and during the follow-up, it was documented the patient died within one week after discharge. CONCLUSIONS: This successful application of the next generation sequencing assisting the rapid diagnosis of Pneumocystis jirovecii and Aspergillus fumigatus coinfection provides a new perspective in the clinical approach against the systematic fungi infections and highlights the potential of this technique in rapid etiological diagnosis.

Therapeutic Drug Monitoring and Pharmacokinetic Analysis of Cyclosporine in a Pediatric Patient with Hemophagocytic Lymphohistiocytosis Complicated by Diabetes Insipidus: A Grand Round.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease. Initial therapy is based on etoposide, dexamethasone, and cyclosporine (CSA). The pharmacokinetics (PKs) of CSA and other drugs are sometimes altered in patients with HLH complicated by diabetes insipidus (DI) but the precise mechanisms remain unknown. METHODS: In this study, the authors present a case of a 4-year-old boy with HLH complicated by DI. CSA concentrations were determined by enzyme multiplied immunoassay technique; noncompartmental PK analysis of the plasma concentration-time data was performed using PKSolver; and linear regression analysis was performed to determine linearity of relationship between urine output and C0 levels of CSA. RESULTS: Although C0 values of CSA were lower than the target levels, the patient was successfully treated and a good clinical outcome was achieved. Linear regression analysis showed a strong negative correlation between urine output and the serum trough concentration (C0) of CSA, pharmacokinetic analysis showed the main PK parameters of CSA as follows: C0, 50.2 mcg/L; peak concentration (Cmax), 723.4 mcg/L; area under the curve0-24, 7478.2 mcg·h/L; clearance, 0.77 L/h/kg, elimination half-life, 5.3 hours, and volume of distribution, 6.0 L/kg. CONCLUSIONS: To the best of the authors' knowledge, this is the first report of the CSA PK profile in a patient with HLH complicated by DI. The authors suppose that a large fluid output and input leads to extensive CSA distribution. These results suggest that the monitoring of the Cmax and area under the curve of CSA might be more clinically and pharmacokinetically significant than that of C0 in patients with HLH complicated by DI. This case highlights the importance of therapeutic drug monitoring and demonstrates PK parameters of CSA in a pediatric patient with HLH complicated by DI.

Modified sequential sac ligation and staged closure technique for the management of giant omphalocele.

PURPOSE: This study aimed to describe sac ligation and sequential closure for the management of giant omphalocele (GO) and analyze its outcomes. METHODS: The medical records of 13 neonates with GO treated at a tertiary general hospital between July 2012 and April 2020 were reviewed. Sac ligation and progressive external compression were performed on most cases immediately after birth. Staged closure with or without a prosthetic patch was conducted after a period of sac suspension. RESULTS: Sac ligation-traction-compression was performed on 12 cases, of which 10 underwent staged closure, one with delayed closure. One patient with coexistent esophageal atresia was deemed ineligible for surgery. Among those who had undergone staged closure, 9 survived; however, one neonate who complicated with bilateral diaphragmatic eventration and severe ventilator-associated pneumonia died from multiple-organ failure. Pentalogy of Cantrell was excluded. One patient in whom primary closure was performed after birth died aged 29 h. Pneumonia was the most common infection among patients (5/13), with three having ventilator-associated pneumonia. The median durations of mechanical ventilation and hospital stay were 22.2 days (range, 1-151) and 44.2 days (range, 2-152), respectively, and 25.6 days and 46.4 days, respectively, among patients with staged closure. Among five infants who required oxygen support for more than 28 days, four had pulmonary hypoplasia. CONCLUSIONS: Aside from abdominal wall defects, other major comorbidities and pulmonary hypoplasia influence the prognosis of GO. Sac ligation and staged closure is a effective choice for GO. TYPE OF STUDY: Retrospective Study Level of Evidence: Level IV.

Intra-abdominal Pressure Has a Good Predictive Power for 28-Day Mortality: A Prospective Observational Study Conducted in Critically Ill Children.

Objective: Elevated intra-abdominal pressure (IAP) is associated with organ dysfunction in critically ill children. Thus far, the predictive value of IAP for mortality remains unknown. Moreover, only few studies determined normal IAP values in pediatric intensive care unit (PICU) children. This study aimed to determine the predictive value of IAP for mortality and calculate normal IAP values in PICU patients. Methods: This prospective observational study was conducted in two PICUs of two tertiary care university teaching hospitals. Patients admitted to the PICU between December 2013 and November 2015 were included. IAP was determined by bladder pressure measurements performed every 8 h until 48 h or until PICU discharge. All patients (except neonatal patients) aged ≤ 14 years who were admitted to the PICUs and had no history of chemical neuromuscular blockade use, neurogenic bladder, or bladder surgery were enrolled. Binary logistic regression was used to analyze the predictive value of IAP for 28-day mortality. Receiver operating characteristic curves were generated to evaluate the prediction effect of IAP. Results: Overall, 229 patients were enrolled. IAP (hazard ratio 1.09, 95% confidence interval [CI] 1.029-1.161, P = 0.004) and lactic acid (hazard ratio 3.04, 95% CI 1.769-5.21, P < 0.001) were independent predictors of 28-day mortality. Additionally, IAP had good predictive power for 28-day mortality, with an area under the curve of 0.74. The optimal cutoff point was 12.13 mmHg (sensitivity 0.58, specificity 0.80). The Youden index was 0.38.Furthermore, 111 (48.47%) patients without high-risk factors or clinical manifestations of IAH were analyzed to determine normal IAP values, which were 7.57 ± 2.85 mmHg (range, 1.98-13.16 mmHg). There were no significant differences in normal IAP values according to different diseases, sex, age, weight, or body mass index (BMI). Conclusions: IAP has good predictive power for 28-day mortality. The optimal IAP cutoff point is 12.13 mmHg. The IAP reference range is 2.0-13.2 mmHg, which was not associated with factors such as sex, age, weight, and BMI in PICU children. We recommend that IAP be included in critical illness scoring systems in the future. IAP >12.13 mmHg may be more suitable for IAH definition in PICU patients.

Airway obstruction as the primary manifestation of infantile thyroid hemangioma.

BACKGROUND: Thyroid hemangioma mostly occurs in adults and is extremely rare in infants. So far, only four pediatric cases of thyroid hemangioma have been reported, one of which has only been clinically diagnosed. Most of the reported cases are of cavernous hemangiomas; capillary hemangioma cases are very rare. To date, there are no reports on capillary thyroid hemangioma in an infant. Therefore, here we present the case of an infant with a primary capillary hemangioma of the thyroid gland, and discuss its treatment and follow-up. CASE PRESENTATION: A2-month-old infant with normal thyroid function presented with airway obstruction as the primary manifestation of thyroid hemangioma. The main symptoms were laryngeal wheezing and dyspnea. Ultrasonography revealed hypoechoic lesions at the lower pole of the bilateral thyroid. Computed tomography revealed enlargement of the thyroid gland, inhomogeneous parenchyma enhancement, and multiple thyroid nodules. However, these imaging modalities were unable to provide an exact diagnosis and the nature of the mass remained unknown prior to an operation. Therefore, a postoperative histopathological examination was undertaken, which revealed capillary thyroid hemangioma. The symptoms significantly improved by a combined treatment involving surgery and oral propranolol. CONCLUSION: When a well-defined capsulate mass is detected on the medical image, the possibility of primary thyroid hemangioma must be considered.

Evaluation of the safety and efficacy of low-dose rasburicase in critically ill children with haematological malignancies.

Background The recommended dose of rasburicase is quite expensive, thus limiting its use. Whether a lower dose of rasburicase would be equally effective for critically ill children, who often have more complicated situations and a higher risk of hospital death, is still unknown. Objective To explore the safety and efficacy of low-dose rasburicase in critically ill children with haematological malignancies who are at high risk of tumour lysis syndrome. Setting A single-centre retrospective cohort study. Method Children with haematological malignancies who had a history of rasburicase exposure during an intensive care unit stay were enrolled. Patients were divided into two groups according to the initial dosage of rasburicase: the standard-dose group (> 0.1 mg/kg/day) and the low-dose group (≤ 0.1 mg/kg/day). The adverse events and short-term prognosis of the two groups were compared. Results Thirty-seven children were selected, 22 in the standard-dose group and 15 in the low-dose group. The most common tumour type was Burkitt's lymphoma (81%), followed by acute lymphoblastic leukaemia (11%). All patients were at high risk of tumour lysis syndrome, and 73% of them had 3 or more tumour lysis syndrome risk factors. The uric acid levels of 90% of patients with hyperuricaemia returned to the normal range within 12 h (100% in the standard-dose group and 75% in the low-dose group, P = 0.083). Eighty-four percent of patients presented serious complications, including tumour lysis syndrome (73%), acute kidney injury (59%), renal replacement treatment (24%), respiratory failure (24%), disseminated intravascular coagulation (16%) and heart failure (11%). There was no significant difference in the incidence of serious complications between the two groups. The overall 7-day and 28-day survival rates after intensive care unit admission were 86% and 84%, respectively. The average length of stay in the intensive care unit was 9.92 ± 5.13 days. Neither the short-term mortality nor the length of stay in the intensive care unit were significantly different between the two groups. Conclusion Low-dose rasburicase is effective and may be an acceptable choice for critically ill children with haematological malignancies.

The Challenges of Apnea Tests in the Determination of Brain Death in Child Patient on Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a life-support modality used in patients with refractory cardiac and/or respiratory failure. ECMO is linked with high risk of neurological complications including brain death. Neurological monitoring during ECMO is important for identifying patients who are suspected of brain death and allows to discontinue ineffective medical treatments. Brain death (BD) is an irreversible cessation of functions of the entire brain, containing the brainstem. The apnea test (AT) is an essential part in the clinical determination of brain death. An apnea test is by neurologic criteria compulsory to confirm BD in China. Apnea test remains a problem for patients receiving ECMO. Currently, there are not any consensus guidelines for the safe performance of AT during ECMO. We report the case of a child on venous-arterial ECMO post-cardiac arrest in whom we performed an apnea test to determine death by neurologic criteria. Decreasing sweep gas flow rate 0.05 L/min every 5 min led to a PaCO2 increase of more than 20 mmHg of apnea. The results of the AT was positive. When he was determined brain dead, his parents decided to donate his organs. AT can be performed on potential donor children on ECMO by decreasing the sweep gas flow. It is a safe and effective method and is important for BD determination.

Massive Hydrothorax and Ascites as the Primary Manifestation of Infection With Clostridium difficile: A Case Report and Literature Review.

Introduction: Clostridium difficile infection (cdi) often occurs with long-term and irregular use of antibiotics. Patients with tumors receiving both antibiotics and chemotherapy are at a high risk of cdi. The symptoms of cdi vary but can include diarrhea, hypovolemia, electrolyte imbalance, hypoproteinemia, toxic megacolon, gastrointestinal tract perforation, disseminated intravascular coagulation, sepsis, and other lethal complications. Here, we report a rare clinical manifestation associated with cdi in a child with lymphoma presenting with massive hydrothorax and ascites. Case Presentation: A 6-year-old girl who was on chemotherapy for lymphoma presented with fever and was treated with intravenous broad-spectrum antibiotics 3 days before admission to our hospital. On the day before admission, she developed abdominal distension and diarrhea. After admission, broad-spectrum antibiotic therapy was initiated, and her hydrothorax and ascites were drained. An initial extensive microbiological evaluation revealed no pathogens, and laboratory tests and imaging studies of the pleural and peritoneal effusions revealed no evidence of cancer. The initial culture results for C. difficile were negative. The patient was diagnosed with CDI only after a positive test result for C. difficile toxin B gene and a repeated stool culture test revealed CDI. Intravenous antibiotics were suspended and replaced with oral vancomycin and Saccharomyces boulardii, which resulted in successful treatment and a good post-discharge outcome. Conclusions: Massive hydrothorax and ascites are rare manifestations associated with CDI. CDI can occur in individuals with risk factors such as those undergoing broad-spectrum antibiotic therapy.