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Background: Although the human adenovirus infection is common, adenovirus infection with liver dysfunction is rare. Methods: To retrospectively analyze and compare the clinical characteristics and outcomes of pediatric patients diagnosed with severe adenovirus pneumonia with and without liver dysfunction, who were admitted to the pediatric intensive care unit of Hunan Children’s Hospital (South China University) between January 2018 and June 2022. Results: Of the 330 severe adenovirus pneumonia cases analyzed (mean age, 19.88 ± 18.26 months), 102 were girls and 228 were boys. They were divided into two groups: those with liver dysfunction (n = 54) and without liver dysfunction (n = 276). Comparison analysis showed no significant between-group differences in body mass index and levels of white blood cells, neutrophils, platelets, albumin, total bilirubin, direct bilirubin, indirect bilirubin, creatine kinase, procalcitonin, creatinine, and urea nitrogen. However, the levels of alanine aminotransferase (175.99 U/L vs 30.55 U/L) and aspartate transaminase (215.96 U/L vs 74.30 U/L) were significantly higher in patients with liver dysfunction compared to those without liver dysfunction. Further analysis showed that pediatric patients with liver dysfunction had a significantly lower percentage of natural killer (NK) cells (6.93% vs 8.71%) and higher mortality rate (22% vs 9%) than those without liver dysfunction. Conclusion: A decrease in serum NK cell levels in pediatric patients with severe adenovirus pneumonia could serve as a marker for monitoring the onset or progression of hepatic damage.

Background. Sepsis can lead to multiple organ damage, of which the heart is one of the most vulnerable organs. Vagal nerve stimulation can reduce myocardial injury in sepsis and improve survival rates. However, the potential impact of low-level tragus stimulation and disparate cell populations on sepsis-induced myocardial dysfunction remains undetermined. Methods. A cardiac single-cell transcriptomic approach was used for characterizing cardiac cell populations that form the heart. Single-cell mRNA sequencing data were used for selecting all cardiac macrophages from CD45+ cells. Then, echocardiography, western blot, flow cytometry, immunofluorescence, and immunohistochemistry were performed to verify the single-cell mRNA sequencing results. Results. Using single-cell mRNA sequencing data, we uncovered the multiple cell populations contributing to myocardial injury in sepsis under low-level tragus stimulation, thereby illustrating a comprehensive map of the cardiac cellular landscape. Pseudotiming analysis in single-cell sequencing showed that low-level vagal nerve stimulation played an anti-inflammatory role by promoting cardiac monocytes into M2 macrophages, which significantly increased α7nAChR expression in heart tissues. Echocardiography assessment indicated that low-level vagal nerve stimulation could also improve cardiac functions in mice with sepsis-induced myocardial dysfunction. In addition, the heart tissues of mice from the sepsis group with low-level tragus stimulation had significantly lower interleukin-1β expression levels than those from the sepsis group. Flow cytometry analysis showed that different acetylcholine concentrations promoted cardiac monocytes into M2 macrophages in in vitro experiments. Conclusion. Low-level tragus stimulation could improve sepsis-induced myocardial dysfunction by promoting cardiac monocytes to M2 macrophages.

Objective: To identify the platelet-related biomarkers in Proliferative diabetic retinopathy (PDR). Methods: Two mRNA expression profiles of PDR (GSE102485 and GSE60436) were downloaded from the Gene Expression Omnibus (GEO) database with the platelet-related genes from gene set enrichment analysis (GSEA) database. A protein-protein interaction (PPI) network was established to screen out hub genes based on the interaction between differentially expressed platelet-related genes (DEPRGs), followed by the prediction of the associated microRNAs (miRNAs), transcription factors (TFs) and drugs, which were taken to establish the regulatory networks of miRNA-hub gene, TF-hub gene and drug-hub gene. To verify the expression of Hub genes, both retinal samples from experimental diabetes mouse models and human retina microvascular endothelial cells (HRMECs) treated with high glucose (HG) were subjected to quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Results: A total of 168 DEPRGs were determined, with 146 genes for upregulation and 22 for downregulation. 9 hub genes (CDC42, GNAI2, LCK, LCP2, LYN, PLCG2, PTPN6, RAC1 and SYK) were eventually screened. 446 miRNAs, 46 TFs and 138 hub gene targeted by drugs were presented after prediction. RAC1 and GNAI2 respectively targeted by 156 miRNAs and 19 TFs lied the most connected hub genes in the miRNA-hub gene and TF-hub gene regulatory networks. Based on the drug-hub gene regulatory network, LCK was targeted by 52 drugs. qRT-PCR results indicated that the expression of LPC2 and PTPN6 was upregulated in both diabetes mouse models and HRMECs treated with HG. Conclusions: Nine hub genes were screened with the prediction of miRNAs, which were targeted by TFs and drugs, and may play an essential role in the progression of PDR, utilized as potential biomarkers and therapeutic targets.

BackgroundKawasaki disease (KD) is a vascular inflammatory disease with unknown pathogenesis. There are few studies on KD combined with sepsis worldwide.PurposeTo provide valuable data regarding clinical characteristics and outcomes related to pediatric patients with KD combined with sepsis in pediatric intensive care unit (PICU).MethodsWe retrospectively analyzed the clinical data of 44 pediatric patients admitted in PICU at Hunan Children’s Hospital with KD combined with sepsis between January 2018 and July 2021.ResultsOf the 44 pediatric patients (mean age, 28.18 ± 24.28 months), 29 were males and 15 were female. We further divided the 44 patients into two groups: KD combined with severe sepsis (n=19) and KD combined with non-severe sepsis (n=25). There were no significant between-group differences in leukocyte, C-reactive protein, and erythrocyte sedimentation rate. Interleukin-6, interleukin-2, interleukin-4 and procalcitonin in KD with severe sepsis group were significantly higher than those in KD with non-severe sepsis group. And the percentage of suppressor T lymphocyte and natural killer cell in severe sepsis group were significantly higher than those in non-severe group, while the CD4+/CD8+ T lymphocyte ratio was significantly lower in KD with severe sepsis group than in KD with non-severe sepsis group. All 44 children survived and were successfully treated after intravenous immune globulin (IVIG) combined with antibiotics.ConclusionChildren who develop with KD combined with sepsis have different degrees of inflammatory response and cellular immunosuppression, and the degree of inflammatory response and cellular immunosuppression is significantly correlated with the severity of the disease.

PURPOSE Chemoresistance remains the primary obstacle threatening the prognosis of retinoblastoma (RB). microRNAs (miRNAs) are acknowledged as critical regulators of drug resistance. This study explored the molecular mechanism of miR-130a-3p affecting the chemosensitivity of RB to vincristine (VCR). METHODS miR-130a-3p expression of human retinal astrocytes and RB cell lines (Y79, WERI-Rb-1, SO-Rb50, and SO-Rb70) was detected using RT-qPCR. VCR-resistant RB cell line Y79/VCR was induced. miR-130a-3p expression of Y79/VCR cell line and its corresponding parental cell line was detected. Y79/VCR cells were subjected to miR-130a-3p overexpression treatment. The cell proliferation was measured using MTT assay, and the IC50 value and drug resistance index were examined using CCK-8 assay. The targeting relationship between miR-130a-3p and PAX6 was predicted through bioinformatics analysis and verified using dual-luciferase assay. Functional rescue experiments were conducted to confirm the role of PAX6 in chemosensitivity of RB cells. The effect of miR-130a-3p on tumorigenesis and VCR sensitivity was observed in vivo. RESULTS miR-130a-3p was downregulated in VCR-resistant RB cells. Overexpression of miR-130a-3p repressed the proliferation of Y79/VCR cells and enhanced chemosensitivity. miR-130a-3p targeted PAX6 expression. Overexpression of PAX6 reversed the effect of miR-130a-3p on chemosensitivity of Y79/VCR cells. Overexpression of miR-130a-3p suppressed tumor growth and reduced VCR resistance in vivo. CONCLUSIONS miR-130a-3p enhanced the chemosensitivity of Y79 RB cells to VCR by targeting PAX6 expression.

Mutations in CSNK2B lead to Poirier-Bienvenu neurodevelopmental syndrome (POBINDS), a rare neurodevelopmental disorder. Only 14 cases of POBINDS have been reported worldwide. The main manifestations are seizures, often tonic–clonic, with or without intellectual disability, growth retardation, and developmental language retardation. We conducted a comprehensive phenotypic mining and trio-whole exome sequencing on six children with POBINDS for gene diagnosis and analyzed the different variants using bioinformatics analysis software and related experiments. This paper reviews previous literature and discusses two common missense variants that lead to structural changes. Among the six patients, four, one, and one had tonic–clonic, myoclonic, and febrile seizures, respectively. Language development disorder, motor development disorder, and developmental delay/intellectual disability (DD/ID) are the main clinical features. All children had de novo mutations in CSNK2B, including three missense variants (c.410G > T/p.(Cys137Phe), c.494A > G/p.(His165Arg), and c.3G > A/p.(Met1Ile)), two splice variants (c.292-2A > T, c.558-3 T > G), and one frameshift variant (c.499delC/p.(Leu167Serfs*60)). Three missense variants were predicted to be harmful by various software programs, and two splicing variants were found to produce new exonic splicing enhancers by the minigene assay. Western blot analysis showed that the frameshift variant resulted in decreased protein expression. According to a literature review, c.3G > A/p.(Met1Ile), c.292-2A > T, c.558-3 T > G, and c.499delC/p.(Leu167Serfs*60) are novel variants of CSNK2B. The decrease or loss of protein function caused by CSNK2B mutations may be a pathogenic factor in this cohort. The severity of the POBINDS phenotype differs, and refractory epilepsy may be accompanied by a more serious DD/ID, language disorder, and motor retardation. At present, there is no specific treatment, and antiepileptic therapy usually requires the combination of two or more anti-epileptic drugs.

Background and aimsDeciding when to suspect hemophagocytic lymphohistiocytosis (HLH) and perform diagnostic tests in patients with acute infection of Epstein-Barr virus (EBV) is challenging, given the high prevalence of EBV infection, the life-threatening risk of EBV-HLH, the relatively low incidence of EBV-HLH, and the wide spectrum of disease presentations. The aim of this study was to develop an EBV-HLH screening model for pediatric patients diagnosed with acute infection of EBV.MethodsAn inpatient cohort with 3183 pediatric patients who were diagnosed with active infection of EBV was used to construct and validate the EBV-HLH screening score model. The model parameters were selected from common laboratory parameters using the method of Akaike Information Criterion-optimal selection through cross-validation under logistic regression. Performance of the score was evaluated and compared with the performance of screening methods using the number of cytopenias lineages.ResultsThe EBV-HLH screening score has five parameters, including hemoglobin, platelet, neutrophil, albumin, and lactate dehydrogenase. Using a cut-of value of 29, the scoring model had a sensitivity of 89.2% and a specificity of 89.5% in the validation set. The false negative rate, false positive rate, positive predictive value, and negative predictive value in the validation set was 10.8%, 10.5%, 26.8%, and 99.5%, respectively, similar to that of the training set.ConclusionsWith five common laboratory parameters, the EBV-HLH score provides a simple tool to assist the identification of EBV patients who require further evaluation of HLH. Further studies are needed to evaluate the generalizability of the score and optimize the diagnose process for EBV-HLH.

Background The coronavirus disease 2019 (COVID-19) pandemic brought remarkable disruption to the ways in which healthcare was delivered. This study aimed to examine changes in pediatric healthcare utilization in Hunan Province, China, during the COVID-19 pandemic. Methods An electronic survey was conducted among 142 hospitals in Hunan Province, China. Using data from January 1 to April 30, 2019 as a reference, the changes in the number of visits for different types of pediatric healthcare between January 1 and April 30, 2020 were calculated. Changes in the number of admissions for infections and injuries were also evaluated. Results The total number of pediatric healthcare presentations decreased by 53.3% in the first four months of 2020. The most remarkable reductions were observed in the utilization of emergency room (ranging from -45.7% to -94.9% among three hospital levels) and observation room (-55.8% to -77.7%); neonatal inpatient care experienced the smallest decreases (-21.2% to -25.5%). Approximately 85% of the total reduction in the number of pediatric inpatient admissions was attributable to the reduction in admissions for infections. A 13.3% increase in the number of admissions for injuries was observed among third-level hospitals. Conclusions The utilization of all types of pediatric healthcare services in Hunan Province declined markedly after the outbreak of COVID-19. The reasons, consequences, and responses to these changes should be addressed in future studies and actions.

ObjectiveTo investigate the epidemiology and the effectiveness of resuscitation from cardiopulmonary arrest (CPA) among critically ill children and adolescents during pediatric intensive care unit (PICU) stay across China.MethodsA prospective multicenter study was conducted in 11 PICUs in tertiary hospitals. Consecutively hospitalized critically ill children, from 29-day old to 18-year old, who had suffered from CPA and required cardiopulmonary resuscitation (CPR) in the PICU were enrolled (December 2017–October 2018). Data were collected and analyzed using the “in-hospital Utstein style.” Neurological outcome was assessed with the Pediatric Cerebral Performance Category (PCPC) scale among children who had survived. Factors associated with the return of spontaneous circulation (ROSC) and survival at discharge were evaluated using multivariate logistic regression.ResultsAmong 11,599 admissions to PICU, 372 children (3.2%) had CPA during their stay; 281 (75.5%) received CPR, and 91 (24.5%) did not (due to an order of “Do Not Resuscitate” requested by their guardians). Cardiopulmonary disease was the most common reason for CPA (28.1% respiratory and 19.6% circulatory). The most frequent initial dysrhythmia was bradycardia (79%). In total, 170 (60.3%) of the total children had an ROSC, 91 had (37.4%) survived till hospital discharge, 28 (11.5%) had survived 6 months, and 19 (7.8%) had survived for 1 year after discharge. Among the 91 children who were viable at discharge, 47.2% (43/91) received a good PCPC score (1–3). The regression analysis results revealed that the duration of CPR and the dose of epinephrine were significantly associated with ROSC, while the duration of CPR, number of CPR attempts, ventricular tachycardia/ventricular fibrillation (VT/VF), and the dose of epinephrine were significantly associated with survival at discharge.ConclusionThe prevalence of CPA in critically ill children and adolescents is relatively high in China. The duration of CPR and the dose of epinephrine are associated with ROSC. The long-term prognosis of children who had survived after CPR needs further improvement.

Recent research suggests that gut microbiota plays an important role in the occurrence and development of excessive weight and obesity, and the early-life gut microbiota may be correlated with weight gain and later growth. However, the association between neonatal gut microbiota, particularly in preterm infants, and excessive weight and obesity remains unclear. To evaluate the relationship between gut microbiota and body mass index (BMI) growth trajectories in preterm infants, we examined microbial composition by performing 16S rDNA gene sequencing on the fecal samples from 75 preterm infants within 3 months after birth who were hospitalized in the neonatal intensive care unit of Hunan Children’s Hospital from August 1, 2018 to October 31, 2019. Then, we collected their physical growth information during 0–10 months. Latent growth mixture models were used to estimate growth trajectories of infantile BMI, and the relationship between the gut microbiota and the BMI growth trajectories was analyzed. The results demonstrated that there were 63,305 and 61 operational taxonomic units in the higher BMI group (n = 18), the lower BMI group (n = 51), and the BMI catch-up group (n = 6), respectively. There were significant differences in the abundance of the gut microbiota, but no significant differences in the diversity of it between the lower and the higher BMI group. The BMI growth trajectories could not be clearly distinguished because principal component analysis showed that gut microbiota composition among these three groups was similar. The three groups were dominated by Firmicutes and Proteobacteria in gut microbiota composition, and the abundance of Lactobacillus in the higher BMI group was significantly different from the lower BMI group. Further intervention experiments and dynamic monitoring are needed to determine the causal relationship between gut microbiota differences and the BMI change.

OBJECTIVES Pancreatic injury is multifactorial and potentially devastating for critically ill children. We aimed to evaluate whether serum amylase and lipase among critically ill children could serve as an independent biomarker to predict pancreatic injury. DESIGN Retrospective cohort. SETTING PICU of a tertiary, pediatric medical center. PATIENTS Seventy-nine autopsies. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS A group of 79 children who died of different causes were investigated by autopsy. They were divided into pancreatic injury group and pancreatic noninjury group according to autopsy findings. Data based on patients' demographics, vital signs, laboratory findings, and clinical features at admission were collected and compared. Logistic regression was used to identify predictive factors for pancreatic injury. Receiver operating characteristic curve was constructed for assessing serum amylase and serum lipase to predicting pancreatic injury. Forty-one patients (51.9%) exhibited the pathologic changes of pancreatic injury. The levels of lactate, erythrocyte sedimentation rate, alanine transaminase, aspartate transaminase, and troponin-I in the injury group were significantly higher than that in the noninjury group, whereas the level of calcium was significantly lower than that in the noninjury group (p < 0.05). Multivariable logistic regression analysis showed that serum amylase, serum lipase, and septic shock were significantly associated with the occurrence rate of pancreatic injury. The statistically significant area under the curve results were as follows: serum amylase: area under the curve = 0.731, at a cutoff value of 97.5, sensitivity = 53.7, and specificity = 81.6; and serum lipase: area under the curve = 0.727, at a cutoff value of 61.1, sensitivity = 36.6, and specificity = 92.1. CONCLUSIONS Serum amylase and lipase could serve as independent biomarkers to predict pancreatic injury in critically ill children.

Patients with hemophagocytic lymphohistiocytosis (HLH) have high risk of early mortality. The purpose of this study was to test the hypothesis that the elevated level of serum myoglobin among patients with HLH is associated with disease severity and increased risk of mortality. We retrospectively investigated the serum myoglobin levels from 155 pediatric patients diagnosed with HLH in the Hunan Children's Hospital, China. The levels of myoglobin and creatine kinase at hospital admission among non-survivors and survivors were compared. The myoglobin level was dichotomized for the estimation of hazard ratio (HR) for mortality. Patients who died within 7 and 30 days of hospitalization had significantly higher myoglobin levels than did survivors (p 0.05). The myoglobin level was negatively associated with the days of survival among non-survivors (Spearman correlation coefficient = - 0.29, p = 0.04). An elevated myoglobin level ( 90 ng/mL) was significantly associated with increased mortality (unadjusted HR = 2.66, 95%CI: 1.41, 5.00, p = 0.0024) and persisted after adjusting for age, Epstein-Barr virus infection, admission department, acute kidney injury, myocardial damage, and shock. In conclusion, an elevated serum myoglobin level was associated with increased risk of early death among pediatric patients with HLH, suggesting the potential of myoglobin to be used as a reference indicator for monitoring and managing of HLH.

BackgroundThe benefits of extracorporeal membrane oxygenation in patients with refractory septic shock remain controversial. Current guidelines on the management of refractory septic shock recommend the consideration of extracorporeal membrane oxygenation as a salvage therapy. The difference between adults and children with septic refractory shock treated with extracorporeal membrane oxygenation has not been previously analyzed. We aimed to review peer-reviewed publications on the role of extracorporeal membrane oxygenation in adults and children with refractory septic shock.MethodsStudies reporting on mortality in both adults and children with refractory septic shock supported with extracorporeal membrane oxygenation published in PubMed, Cochrane Library, and Embase databases were included in the meta-analysis. Study eligibility was independently assessed by two authors, and disagreements were resolved by a third author. The outcome measure was survival at discharge. Subgroup analysis included the adult and pediatric groups.ResultsOf the 293 articles screened, 14 original articles were identified for systematic review and meta-analysis. The cumulative estimate of survival (14 studies, 535 patients) in the cohort was 39% (95% confidence interval [CI]: 27–51%). During the subgroup analysis, the cumulative estimate of survival at discharge in the adult group (6 studies, 276 patients) in the cohort was 18% (95% CI: 10–27%), and that in the pediatric group (8 studies, 259 patients) was 53% (95% CI: 47–59%).ConclusionsThe survival rate of adults with refractory septic shock requiring extracorporeal membrane oxygenation was 18%, and children with refractory septic shock requiring extracorporeal membrane oxygenation had a higher survival rate (53%) than adults.

Purpose Our aim was to investigate the age-associated plasma protein profiles in pneumonia-derived sepsis between infants and toddlers and identify potential age-adapted prognostic markers for poor outcome of pneumonia-derived pediatric sepsis. Experimental design A nested case-control study strategy was applied. The plasma proteomes of pneumonia-derived pediatric septic patients with different outcomes between infants and toddlers were respectivly analysed compared to their age-matched controls. Results Compared to toddlers, pneumonia-derived sepsis in infants was characterized by increased upregulation of protein processing in the ER, proteasome and antigen processing and presentation; and reduced downregulation in complement and coagulation cascades and cholesterol metabolism. Among them, the pentose phosphate pathway as well as the complement and coagulation cascades were possibly associated with poor outcome of pneumonia-derived sepsis. Furthermore, we confirmed that HP, THBS1, and SAA1/2 were potential prognostic markers for poor outcome of pneumonia-derived sepsis in infant patient groups. Conclusions and clinical relevance Age-associated plasma protein profiles of pneumonia-derived pediatric septic patients provided potential age-adapted biomarkers for a more precise prognosis of poor outcome in pneumonia-derived pediatric sepsis and helped to improve the survival of septic children. This article is protected by copyright. All rights reserved.

Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder. How to stratify high risk patients is one of the current challenges for the treatment of HLH. HLH patients usually fulfill multiple but not all eight diagnostic criteria. Different combinations of the fulfilled criteria may naturally cluster into previously undescribed subsets or phenotypes that may have different pathophysiology and demonstrate different risks for a poor outcome. The objectives of this study were to identify HLH subgroups according to the fulfillment of diagnostic criteria and evaluate the risk of multiple organ dysfunction syndrome (MODS) and 30-day mortality for subgroups. We retrospectively collect medical records of patients with discharge diagnosis of HLH between June 2015 and October 2018 from a tertiary children’s hospital in China. Latent class analysis was used to identify class defining variables from HLH diagnostic items, and subgroups were defined according to different combinations of the class defining variables. Results Triglyceride and fibrinogen were identified as the class defining variables. When evaluated in combinations, patients with hypertriglyceridemia and normal fibrinogen levels during hospitalization had the lowest risks for MODS (27.8%, OR = 1) and 30-day mortality (18.8%, OR = 1), and patients with normal triglyceride and hypofibrinogenemia had the highest risks for MODS (86.2%, OR = 16.24, P = 0.0002) and 30-day mortality (57.1%, OR = 5.78, P = 0.0187). The fulfillment status of hypertriglyceridemia and hypofibrinogenemia within 72 h of hospital admission was also associated with the risk of adverse outcomes. Conclusions The fulfillment status of hypertriglyceridemia and hypofibrinogenemia were associated with the risks of MODS and 30-day mortality among pediatric HLH patients. Further studies are needed to validate this association and investigate its clinical utility in the severity evaluation for HLH.

Purpose Chemoresistance remains the primary obstacle threatening the prognosis of retinoblastoma (RB). microRNAs (miRNAs) are acknowledged as critical regulator of drug resistance. This study explored the molecular mechanism of miR-130a-3p affecting the chemosensitivity of RB to vincristine (VCR). Methods miR-130a-3p expression of VCR-sensitive and VCR-resistant RB tissues was detected using RT-qPCR. VCR-resistant RB cell line Y79/VCR was induced. miR-130a-3p expression of Y79/VCR cell line and its corresponding parental cell line was detected. Y79/VCR cells were subjected to miR-130a-3p overexpression treatment. The cell proliferation was measured using MTT assay, and the IC50 value and drug resistance index were examined using CCK-8 assay. The targeting relationship between miR-130a-3p and PAX6 was predicted through bioinformatics analysis and verified using dual-luciferase assay. Functional rescue experiments were conducted to confirm the role of PAX6 in chemosensitivity of RB cells. The effect of miR-130a-3p on tumorigenesis and VCR sensitivity was observed in vivo. Results miR-130a-3p was downregulated in VCR-resistant RB tissues and cells. Overexpression of miR-130a-3p repressed the proliferation of VCR-resistant RB cells and enhanced chemosensitivity. miR-130a-3p targeted PAX6 expression. Overexpression of PAX6 reversed the effect of miR-130a-3p on chemosensitivity of RB. Overexpression of miR-130a-3p suppressed tumor growth and reduced VCR resistance in vivo. Conclusion miR-130a-3p enhanced the chemosensitivity of RB cells to VCR by targeting PAX6 expression.

Objective This prospective study was performed to explore the change in sacrococcygeal pressure during an operation under general anesthesia in the supine position and identify the correlation between pressure injury and body mass index. Methods This study involved 99 patients who underwent general anesthesia. Sacrococcygeal pressure was measured and recorded at seven time points: before general anesthesia, 5 minutes after general anesthesia, and 1, 2, 3, 4, and 5 hours after the beginning of the operation. The pressure change at each time point was compared, and the factors affecting the pressure were analyzed. Results The correlation analysis showed that the operation time was significantly and positively associated with the occurrence of pressure injury. Conclusion Perioperative management should be strengthened to speed up the surgical process and shorten the operation time, which will help to reduce the occurrence of intraoperative pressure injury.

Phenotypes of some rare genetic diseases are atypical and it is a challenge for pediatric intensive care units (PICUs) to diagnose and manage such patients in an emergency. In this study, we investigated 58 PICU patients (39 deceased and 19 surviving) in critical ill status or died shortly without a clear etiology. Whole exome sequencing was performed of 103 DNA samples from their families. Disease-causing single-nucleotide variants (SNVs) and copy number variants (CNVs) were identified to do genotype-phenotypes analysis. In total, 27 (46.6%) patients received a genetic diagnosis. We identified 34 pathogenic or likely pathogenic SNVs from 26 genes, which are related to at least 19 rare diseases. Each rare disease involved an isolated patient except two patients caused by the same gene ACAT1. The genotypic spectrum was expanded by 23 novel SNVs from gene MARS1, PRRT2, TBCK, TOR1A, ECE1, ARX, ZEB2, ACAT1, CPS1, VWF, NBAS, COG4, and INVS. We also identified two novel pathogenic CNVs. Phenotypes associated with respiratory, multiple congenital anomalies, neuromuscular, or metabolic disorders were the most common. Twenty patients (74.1%) accompanied severe infection, 19 patients (70.1%) died. In summary, our findings expanded the genotypes and phenotypes of 19 rare diseases from PICU with complex characteristics.

The difficulties and challenges of applying the HLH-2004 diagnostic criteria to early identification and diagnosis of haemophagocytic lymphohistiocytosis have been fully addressed in previous studies. However, the distribution of the diagnostic time lag of haemophagocytic lymphohistiocytosis and related patient characteristics remain unclear. This study investigated the time lags between symptom onset and diagnosis and between hospital admission and diagnosis among pediatric patients with haemophagocytic lymphohistiocytosis, and identified factors that associated with a shorter or longer diagnostic time lag. The cohort of patients with haemophagocytic lymphohistiocytosis was drawn from a tertiary children's hospital and consisted of 122 pediatric patients. The distributions of symptom-to-diagnosis and admission-to-diagnosis time lags were assessed. Clinical characteristics within 48 h of admission and the fulfillment of HLH-2004 diagnostic criteria were compared among admission-to-diagnosis time lag categories. Logistic regression analyses were conducted to identify factors associated with an admission-to-diagnosis time lag >3 days. The median interval from first symptom onset to HLH diagnosis was 12 days (range 4–71 days) and the median interval from hospital admission to HLH diagnosis was 2 days (range 0–23 days). The following factors were negatively associated with admission-to-diagnosis > 3 days: Epstein–Barr virus infection; admission through pediatric intensive care unit; diagnosis established without NK-cell activity and soluble CD25 tests; the performance of all readily available diagnostic tests for HLH (within 48 and 72 h); concurrent fever, splenomegaly, and cytopenias within 48 h; hemophagocytosis, hypertriglyceridemia and/or hypofibrinogenemia within 48 h; and elevated ferritin, total bilirubin, alanine aminotransferase, and prothrombin time within 48 h. Our findings suggest that performance of adequate diagnostic tests for HLH is essential for early diagnosis of HLH. Once suspected, immediate and adequate diagnostic tests for HLH should be arranged for PICU patients. Improvements in diagnostic procedures and monitoring plans are needed to promote early diagnosis of HLH.

Background: Extracorporeal membrane oxygen (ECMO) has used for rescuing severe pediatric acute respiratory distress syndrome (PARDS) for half a century. Prone position ventilation (PPV) has been suggested according to the surviving sepsis campaign (SSC) guideline in children in 2020. We aimed to compare the outcomes and effect of PARDS patients with ECMO+PPV and ECMO only.Design: Retrospective Multicenter pair-matched StudySetting: In the present study, propensity score matching was conducted and the outcomes of severe PARDS patients were analyzed. The effect of PPV was compared as well. The efficiency of PPV included PaO2, Oxygen Index (OI), PaO2/FiO2, compliance of respiratory system and resistance of airway. The primary outcome was hospital mortality. Secondary outcomes included ECMO running time, PICU time, hospital days and mechanical ventilation time of survivors. Patients: 137 PARDS patients with criteria of ECMO from 11 hospitals in 5 years.Interventions: No interventions.Measurements and Main Results: Among 137 patients, 93 patients received ECMO+PPV at the same time and 44 patients didn’t. After matching, we got 34 pairs. For the survivors receiving ECMO+PPV, the PaO2, OI and PaO2/FiO2 increased significantly during the PPV period (PConclusions: By far, there has been no ECMO+PPV efficiency study in PARDS patients. This study found that PPV was associated with improved oxygen state during ECMO. However, PPV was not associated with survival rate with PARDS patients on ECMO. Clinical Trial Registration: This study was registered at http://www.chictr.org.cn/index.aspx (chiCTR.gov; Identifier: ChiCTR1800019555). Registered 18 November 2018. Name of the registry: Extracorporeal membrane oxygenation in critical ill children with severe acute respiratory distress syndrome - A multicenter study.Take Home Message:1. Our study investigated prone position ventilation (PPV) could improve the oxygen state during ECMO for patients with severe PARDS.2. The results indicated PPV had no influence on the mortality of PARDS with ECMO.

Background Hemophagocytic lymphohistiocytosis (HLH) is a relatively rare and life-threatening disorder. Early mortality remains significantly high among patients with HLH. Our aim was to investigate clinical features and risk factors associated with 7-day and 30-day mortality among pediatric HLH patients. We retrospectively collected medical records of patients with discharge diagnosis of HLH between August 2014 and October 2018 from a tertiary children’s hospital in China. The main outcome measures were the 7-day and 30-day outcome after hospital admission. The associations between symptoms, concomitant diagnoses, laboratory test results, and the risk of 7-day and 30-day mortality were examined. Results Among 160 pediatric HLH patients, 18 (11.3%) patients were deceased within 7 days after admission, and 46 (28.8%) patients were deceased within 30 days. The identified strong risk factors (OR > 10 and p Conclusions The identified risk factors could help to stratify patients with high risk of early death, and need to be considered in the development of treatment protocols. As early mortality of HLH remains high, studies are needed to investigate how to initiate adequate HLH-directed treatment strategies for patients at higher risk of early death.

Recent studies have reported that the imbalance of T helper 1 cell (Th1), Th17 and regulatory T cell (Treg) have been confirmed to play a vital role in the development of sepsis and other inflammatory diseases. Baicalin (BA) has anti-inflammatory properties and improves survival in sepsis. We investigated whether baicalin could regulate Th1, Th17 and Treg responses to ameliorate sepsis-associated pancreatic injury through the ras homolog family member A (RhoA)-Rho kinase (ROCK) pathway. The sepsis model was established by using the cecal ligation and puncture (CLP) method. Fifty mice were randomly divided into five groups (n = 10): sham group, model group, low-dose group (BA-L, 100 mg/kg of baicalin), medium-dose group (BA-M, 200 mg/kg of baicalin) and highdose group (BA-H, 300 mg/kg of baicalin). The effects of baicalin on the pancreatic injury, on changes of Th1, Th17 and Treg cells in vivo and in vitro, on RhoA, ROCK1 and signal transducer and activator of transcription (STAT) signaling pathways, and on levels of interferon-γ (IFN-γ), interleukin-17 (IL-17) and IL-10 were examined. Treatment of the CLP mice with baicalin significantly reduced the extent, scope and severity of the pathological changes of sepsis-associated pancreatic injury. Baicalin evidently reduced Th1 and Th17 cells and increased Treg cells in peripheral blood, spleen, pancreatic tissue and significantly inhibited T-box protein expressed in T cells (T-bet), retinoic acid receptor-related orphan receptor γt (RORγt) and increased forkhead/winged helix transcription factor (Foxp3) expressions in the pancreatic tissue. Baicalin reduced the expressions of RhoA, ROCK1, phosphorylated STAT4 (p-STAT4), p-STAT3 and increased the expression of p-STAT5 in peripheral blood, spleen and pancreatic tissue. Baicalin reduced the expressions of IFN-γ and IL-17 and increased the IL-10 in serum and pancreatic tissue. Baicalin is capable of ameliorating sepsis-associated pancreatic injury and regulating Th1, Th17 and Treg responses in sepsis. The present study provided a potential adjunctive therapy for treating pancreatic injury in sepsis, and further study is needed to reveal its deeper mechanisms.

Objective: The aim of this study was to determine whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) can predict impending brainstem encephalitis, pulmonary edema, pulmonary hemorrhage, cardiopulmonary failure, and death in children with severe enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD). Methods: Plasma NT-proBNP levels of 282 children with severe EV71-associated HFMD were measured. Results: NT-proBNP levels were significantly higher in patients with elevated blood glucose (>7.8 mmol/l) and increased white blood cell counts (>14 × 109/l). HFMD patients who had no complications had significantly lower NT-proBNP values than patients who died or had complications (p

Hand, foot, and mouth disease (HFMD) is endemic in the Pacific region, especially in mainland China. The case-fatality ratio of HFMD is increasing steadily. Knowledge of the changing epidemiology of HFMD in different regions is necessary for implementing appropriate intervention strategies. In this study, we describe the clinical and epidemiological characteristics of HFMD in Hunan Children’s Hospital between 2013 and 2017. A total of 7203 patients with HFMD were admitted, with complication and mortality rates of 35.62% and 0.78%, respectively. The total number of children with HFMD, proportion of severely ill children, and HFMD mortality rate were the highest in 2014. The number of cases caused by EV-A71 and CV-A16 decreased continuously, while the number of cases caused by ‘other enteroviruses’ increased yearly since 2014, suggesting that other enteric viruses will gradually replace EV-A71 and CV-A16 as the main pathogenic HFMD agents. Furthermore, EV-A71 and mixed infections accounted for the high case fatality rates in children with severe HFMD, among whom EV-A71 infection resulted in the highest complication and mortality rates; the mild form of the disease was dominated by ‘other enteroviruses’. In conclusion, the changing etiological pattern highlights the need to improve pathogen surveillance and vaccine strategies for HFMD control.

Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder characterized by a defect in the liver-specific peroxisomal enzyme alanine-glyoxylate and serine-pyruvate aminotransferase (AGT). This disorder results in hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis. Three forms of PH1 have been reported. Data on the infantile form of PH1 are currently limited in literature. Despite the fact that China is the most populated country in the world, only a few AGXT mutations have been reported in several Chinese PH1 patients. In the present study, we investigated a Chinese family in which two siblings are affected by the infantile form of PH1. Sanger sequencing was carried out on the proband, but the results were misleading. Two novel missense mutations (c.517T > C/p.Cys173Arg and c.667A > C/p.Ser223Arg) of the AGXT gene were successfully detected through whole-exome sequencing. These two mutations occurred in the highly conserved residues of the AGT. Four software programs predicted both mutations as the cause of the disease. A postmortem examination was performed and revealed the occurrence of global nephrocalcinosis on both kidneys. The crystals were collected and analyzed as calcium oxalate monohydrate. This study extends the knowledge on the clinical phenotype–genotype correlation of the AGXT mutation. That is, (i) two novel missense mutations were identified for the infantile form of PH1 and (ii) the same AGXT genotype caused the same infantile form of PH1 within the family.

Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder characterized by a defect in the liver-specific peroxisomal enzyme alanine-glyoxylate and serine-pyruvate aminotransferase (AGT). This disorder results in hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis. Three forms of PH1 have been reported. Data on the infantile form of PH1 are currently limited in literature. Despite the fact that China is the most populated country in the world, only a few AGXT mutations have been reported in several Chinese PH1 patients. In the present study, we investigated a Chinese family in which two siblings are affected by the infantile form of PH1. Sanger sequencing was carried out on the proband, but the results were misleading. Two novel missense mutations (c.517T > C/p.Cys173Arg and c.667A > C/p.Ser223Arg) of the AGXT gene were successfully detected through whole-exome sequencing. These two mutations occurred in the highly conserved residues of the AGT. Four software programs predicted both mutations as the cause of the disease. A postmortem examination was performed and revealed the occurrence of global nephrocalcinosis on both kidneys. The crystals were collected and analyzed as calcium oxalate monohydrate. This study extends the knowledge on the clinical phenotype–genotype correlation of the AGXT mutation. That is, (i) two novel missense mutations were identified for the infantile form of PH1 and (ii) the same AGXT genotype caused the same infantile form of PH1 within the family.

Outbreaks of hand, foot and mouth disease (HFMD) have increased recently, as has the case fatality rate in severe cases. No scoring system currently exists to predict mortality risk for severe HFMD in previous study. We retrospectively collected laboratory parameters for 546 patients with severe HFMD (a derivation and a validation cohort) at Hunan Children’s Hospitals between January 2012 and December 2014. We developed a mortality risk score comprising four laboratory parameters: blood glucose (GLU), white blood cells (WBC), lactate (LAC), and N-terminal-probrain natriuretic peptide (NT-proBNP). Using an “optimal” cutoff score of 4, the sensitivity, specificity, positive predictive value and negative predictive value was 88.00%, 96.14%, 62.86% and 99.08%, respectively, in the derivation cohort. Among severe HFMD patients with low- and high-risk scores in the validation cohort, case fatality rates were 1.49% and 74.07%, respectively. According to the “optimal” cut-off in the derivation cohort, the sensitivity, specificity, positive predictive value, and negative predictive value were 80.95%, 93.83%, 62.96% and 97.44%, respectively, in the derivation cohort. The mortality risk score demonstrated good discrimination (AUC > 0.9) and calibration (P > 0.05) in both cohorts. The mortality risk score, comprising WBC, GLU, LAC and NT-proBNP, has been demonstrated good discrimination and calibration in the both cohorts.

Pediatric sepsis is a burdensome public health problem. Assessing the mortality risk of pediatric sepsis patients, offering effective treatment guidance, and improving prognosis to reduce mortality rates, are crucial. We extracted data derived from electronic medical records of pediatric sepsis patients that were collected during the first 24 hours after admission to the pediatric intensive care unit (PICU) of the Hunan Children's hospital from January 2012 to June 2014. A total of 788 children were randomly divided into a training (592, 75%) and validation group (196, 25%). The risk factors for mortality among these patients were identified by conducting multivariate logistic regression in the training group. Based on the established logistic regression equation, the logit probabilities for all patients (in both groups) were calculated to verify the model's internal and external validities. According to the training group, 6 variables (brain natriuretic peptide, albumin, total bilirubin, D-dimer, lactate levels, and mechanical ventilation in 24 hours) were included in the final logistic regression model. The areas under the curves of the model were 0.854 (0.826, 0.881) and 0.844 (0.816, 0.873) in the training and validation groups, respectively. The Mortality Risk Model for Pediatric Sepsis we established in this study showed acceptable accuracy to predict the mortality risk in pediatric sepsis patients.

Background: Multiple severity scoring systems have been devised and evaluated in adult sepsis, but a simplified scoring model for pediatric sepsis has not yet been developed. This study aimed to develop and validate a new scoring model to stratify the severity of pediatric sepsis, thus assisting the treatment of sepsis in children. Methods: Data from 634 consecutive patients who presented with sepsis at Children’s hospital of Hunan province in China in 2011–2013 were analyzed, with 476 patients placed in training group and 158 patients in validation group. Stepwise discriminant analysis was used to develop the accurate discriminate model. A simplified scoring model was generated using weightings defined by the discriminate coefficients. The discriminant ability of the model was tested by receiver operating characteristic curves (ROC). Results: The discriminant analysis showed that prothrombin time, D-dimer, total bilirubin, serum total protein, uric acid, PaO2/FiO2 ratio, myoglobin were associated with severity of sepsis. These seven variables were assigned with values of 4, 3, 3, 4, 3, 3, 3 respectively based on the standardized discriminant coefficients. Patients with higher scores had higher risk of severe sepsis. The areas under ROC (AROC) were 0.836 for accurate discriminate model, and 0.825 for simplified scoring model in validation group. Conclusions: The proposed disease severity scoring model for pediatric sepsis showed adequate discriminatory capacity and sufficient accuracy, which has important clinical significance in evaluating the severity of pediatric sepsis and predicting its progress.

Background: Multiple severity scoring systems have been devised and evaluated in adult sepsis, but a simplified scoring model for pediatric sepsis has not yet been developed. This study aimed to develop and validate a new scoring model to stratify the severity of pediatric sepsis, thus assisting the treatment of sepsis in children. Methods: Data from 634 consecutive patients who presented with sepsis at Children’s hospital of Hunan province in China in 2011-2013 were analyzed, with 476 patients placed in training group and 158 patients in validation group. Stepwise discriminant analysis was used to develop the accurate discriminate model. A simplified scoring model was generated using weightings defined by the discriminate coefficients. The discriminant ability of the model was tested by receiver operating characteristic curves (ROC). Results: The discriminant analysis showed that prothrombin time, D-dimer, total bilirubin, serum total protein, uric acid, PaO2/FiO2 ratio, myoglobin were associated with severity of sepsis. These seven variables were assigned with values of 4, 3, 3, 4, 3, 3, 3 respectively based on the standardized discriminant coefficients. Patients with higher scores had higher risk of severe sepsis. The areas under ROC (AROC) were 0.836 for accurate discriminate model, and 0.825 for simplified scoring model in validation group. Conclusions: The proposed disease severity scoring model for pediatric sepsis showed adequate discriminatory capacity and sufficient accuracy, which has important clinical significance in evaluating the severity of pediatric sepsis and predicting its progress.

To assess the performance of pediatric risk of mortality (PRISM), pediatric index of mortality 2 (PIM2) in predicting mortality in critically ill pediatric patients via a prospective study.The outcome and the variables required to calculate PRISM and PIM2 were collected. The efficiency of PRISM and PIM2 in differentiation between death and survival by calculating the area under the receiver operating characteristic curve (ROC). Calibration across deciles of risk was evaluated using the Hosmer-Lemeshow goodness-of-fit χ(2) test.A total of 412 critically ill pediatric patients transferred to Hunan Children's Hospital during August 1, 2012 and May 31, 2013 were enrolled in the study, and more than two-thirds of the children were suffering from respiratory and miscellaneous diseases; 45 (10.9%) inter-hospital transport of critically ill pediatric patients died at the time of hospitalization. The expected number of deaths were 45.01 by PRISM, and the expected number of deaths were 44.99 by PIM2. The expected mortality rate was 10.9% for PRISM or PIM2. The standardized mortality rate was 1.000 (0.710-1.290) for PRISM and 1.000 (0.710-1.290) for PIM2. The Hosmer-Lemeshow test gave a chi-square of 8.75 (P=0.364) for PRISM and 22.75 (P0.05) for PIM2, PRISM had better fitting with the actual mortality than PIM2. The area under the receiver-operating characteristics (ROC) curve (95% confidence intervals, CI) were 0.829 (0.768-0.890) for PRISM and 0.758 (0.667-0.849) for PIM2.Although the PIM2 test is less well calibrated overall, both PRISM and PIM2 can offer a good capacity for discriminating between survivors and moribund patients. The good performance of PRISM and PIM2 are demonstrated in predicting mortality probability in critically ill pediatric patients.

Objectives The aim of this study is to describe blood lead levels (BLLs) and the prevalence of elevated blood lead levels (EBLLs) in children aged 0–6 years old and to analyze the BLL trend in children from 2009 to 2013 in China. Methods A total of 124,376 children aged 0–6 years old were recruited for this study from January 1st 2009 to December 31st 2013. Their blood lead levels were analyzed using atomic absorption spectrometry. Results The median BLL was 64.3 μg/L (IQR: 49.6–81.0), and the range was 4.3–799.0 μg/L. Blood lead levels were significantly higher in boys (66.0 μg/L) than in girls (61.9 μg/L) (P

This study was designed with the aim of comparing the performances of the pediatric risk of mortality (PRISM), pediatric index of mortality (PIM), and revised version pediatric index of mortality 2 (PIM2) models in a pediatric intensive care unit (PICU) in China.A total of 852 critically ill

Although beta cell dysfunction has been proved to predict prognosis among humans and animals, its prediction on severity of disease remains unclear among children. The present study was aimed to examine the relationship between beta cell dysfunction and severity of disease among critically ill children. This prospective study included 1146 critically ill children, who were admitted to Pediatric Intensive Care Unit (PICU) of Hunan Children's Hospital from November 2011 to August 2013. Information on characteristics, laboratory tests, and prognostic outcomes was collected. Homeostasis model assessment (HOMA)-β, evaluating beta cell function, was used to divide all participants into 4 groups: HOMA-β = 100% (group I, n = 339), 80% ≤ HOMA-β < 100% (group II, n = 71), 40% ≤ HOMA-β < 80% (group III, n = 293), and HOMA-β < 40% (group IV, n = 443). Severity of disease was assessed using the worst Sequential Organ Failure Assessment (SOFA) score, Pediatric Risk of Mortality (PRISM) III score, incidence of organ damage, septic shock, multiple organ dysfunction syndrome (MODS), mechanical ventilation (MV) and mortality. Logistic regression analysis was used to evaluate the risk of developing poor outcomes among patients in different HOMA-β groups, with group I as the reference group. Among 1146 children, incidence of HOMA-β < 100% was 70.41%. C-peptide and insulin declined with the decrement of HOMA-β (P

To obtain the gene encoding retinal specific Rho promoter therefore to prepare for exogenous gene transcription and expression in retina.Extract the genomic DNA of a BLAB/c mice . The Rho promoter DNA were then amplified by PCR, the product of which was subcloned into PcDNA3.1 +vector. After identification by restriction enzymes, the recombinant PcDNA3.1+vectors were subjected to sequence analysis.The fragments of the promoter as amplified by PCR were of predicted length. Digestion with HindIII and NheI proved correct insertion of the target fragments with expected length into the recombinant PcDNA3.1+vectors. As indicated by homology analysis the Rho promoter was highly conservative, and the Rho promoter we got had hole homology as reported by Boulanger A etc.Retinal specific Rho promoter has been successfully cloned, thus making possible the subsequent research as the mechanism and gene therapy of retina.

To evaluate the nibble technology in the therapy of diabetic retinopathy.Eighty-three patients (ninety-two eyes) with proliferative diabetic retinopathy were treated in our department. All the patients received a standard pars plana vitrectomy. Fifty-two of them (fifty-eight eyes) were treated with nibble technology, while the other thirty-one (thirty-four eyes), who were treated with common procedure to tear the proliferative membrane, were served as a control group.The operative complication of iatrogenic retinal tears was observed in 2 eyes of the test group and 7 eyes of the control group (P0.05). Another operative complication of hemorrhage was observed in 4 eyes of the test group and 15 eyes of the control group (P0.01). There were 6 eyes of the test group and 5 eyes of the control group presented with grade-III postoperative responds (P0.01).The nibble technology is safe in the therapy of proliferative diabetic retinopathy and could reduce the complications during or after the operation.

To document the anatomic and functional improvement of six patients with branch retinal vein occlusion (BRVO) following successful arteriovenous adventitial sheathotomy (AAS).Retrospective study of 6 patients (6 eyes) with BRVO treated with AAS. All patients were not eligible for laser photocoagulation and had both macular edema and intraretinal hemorrhage. The visual acuity was in the range of 0.4 to 0.02. All patients underwent pars plana vitrectomy and AAS. The clinical improvement was determined by fundus photograph, fluorescein angiography (FAG), optical coherence tomography (OCT) and multifocal electroretinography (ERG). All patients were followed postoperatively for an average of 20 months ranging from 12 to 24 months.Sheathotomy and decompression of the arteriole/venule (A/V) crossing were achieved in all 6 patients. 5 patients have improved their best-corrected visual acuity 4 lines or more. The best one could reach to 1.0. One month after the operation, fundus photograph and FAG demonstrated the resolution of intraretinal hemorrhage, reduction of non-perfusion area and apparent resolution of retinal venous dilation and tortuosity. OCT confirmed remarkable reduction of retinal thickness. The microcysts at the fovea diminished. Multifocal ERG showed the recovery of the central peak at the macular and the peripheral response density. However, capillary nonperfusion area and microaneurysm were found out by FAG in four patients at the points distal to the sheathotomy three months after the operation.Anatomic and functional improvement of retina can be achieved in patients with BRVO through AAS. However, the capillary nonperfusion and microaneurysm may follow this surgical procedure in some cases that need further treatment with laser photocoagulation. The better visual improvement may be expected in the patients with earlier surgical intervention.