[A multicenter prospective study on early identification of refractory Mycoplasma pneumoniae pneumonia in children].

Objective: To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods: The prospective multicenter study was conducted in Zhejiang, China from May 1st, 2019 to January 31st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results: A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95%CI 0.593-0.771, P<0.01). Conclusion: In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Multi-locus sequence typing and phylogenetics of Cryptococcus neoformans AD hybrids.

Hybrid AD strains of the human pathogenic Cryptococcus neoformans species complex have been reported from many parts of the world. However, their origin, diversity, and evolution are incompletely understood. In this study, we analyzed 102 AD hybrid strains representing 21 countries on five continents. For each strain, we obtained its mating type and its allelic sequences at each of the seven loci that have been used for genotyping haploid serotypes A and D strains of the species complex by the Cryptococcus research community. Our results showed that most AD hybrids exhibited loss of heterozygosity at one or more of the seven analyzed loci. Phylogenetic and population genetic analyses of the allelic sequences revealed multiple origins of the hybrids within each continent, dating back to one million years ago in Africa and up to the present in other continents. We found evidence for clonal reproduction and long-distance dispersal of these hybrids in nature. Comparisons with the global haploid serotypes A and D strains identified new alleles and new haploid multi-locus genotypes in AD hybrids, consistent with the presence of yet-to-be discovered genetic diversity in haploid populations of this species complex in nature. Together, our results indicate that AD hybrids can be effectively genotyped using the same multi-locus sequencing type approach as that established for serotypes A and D strains. Our comparisons of the AD hybrids among each other as well as with the global haploid serotypes A and D strains revealed novel genetic diversity as well as evidence for multiple origins and dynamic evolution of these hybrids in nature.

[Hereditary pulmonary hypertension family with BMPR2 gene variation: a case report and literature review].

Objective: To describe the clinical characteristics, diagnosis, genetic features and treatment of hereditary pulmonary hypertension complicated with suspected hereditary hemorrhagic telangiectasia (HHT). Methods: Firstly, we summarized and analyzed the clinical data of two cases of suspected HHT admitted to the Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University. Secondly, the genes of peripheral blood of patients and their families were completely sequenced and sanger sequencing was performed to verify the variation sites, and then the mRNA deletion caused by the variation was further verified. Thirdly, "HHT" "FPAH" and "BMPR2 gene variation" were used as keywords,and the related literatures of Wanfang database and PubMed database from January 2000 to November 2021 were searched and reviewed. Results: We found two patients in a family from Yiyang, Hunan province, who had symptoms of hemoptysis or pulmonary hypertension without epistaxis or other clinical features of HHT. However, both patients had pulmonary vascular abnormalities and pulmonary hypertension in their lungs. We found that BMPR2 gene variation (NM_001204.7:c.1128+1G>T) was positive and ENG, ACVRL1 and SMAD4 genes were negative. Family analysis and Sanger verification were carried out on 16 individuals in 4 generations of the family (7 of whom were found to carry the mutant gene), and then transcriptional level mRNA sequencing further confirmed that the variation resulted in the deletion of exon 8 and exon 9, and amino acid sequence estimation revealed that the amino acids of the protein from 323 to 425 were deleted. We thought that the incomplete translation of BMPR2 gene could lead to BMPRⅡ dysfunction. Therefore, it was diagnosed as hereditary pulmonary hypertension with suspected HHT. Both patients were suggested to reduce the pulmonary artery pressure, and at the same time, the whole-body imaging examination should be performed to screen other arteriovenous malformations, and the annual cardiac color Doppler ultrasound should be reviewed to evaluate the changes of pulmonary artery pressure. Conclusions: Hereditary pulmonary hypertension (HPAH) is a group of diseases with increasing pulmonary vascular resistance caused by genetic factors, including familial PAH and simple PAH. Variation in the BMPR2 gene is an important pathogenic factor of HPAH. Therefore, we should pay attention to the inquiry of family history when we clinically encounter young patients with pulmonary hypertension. If the cause is unknown, genetic testing is recommended. HHT is a rare autosomal dominant genetic disease. The possibility of this disease should be considered in clinical manifestations such as familial pulmonary vascular abnormality, pulmonary hypertension and recurrent epistaxis. There is no effective specific treatment for HPAH and HHT, which are treated symptomatically (including blood pressure reduction and hemostasis, etc.). It is suggested for these patients that pulmonary artery pressure should be dynamically monitored and have genetic counseling before giving birth.

Comparison study of three laparoscopic ligation procedures for pediatric inguinal hernia: a multicenter cohort of 5523 cases.

PURPOSE: Single-site laparoscopic percutaneous extraperitoneal ligation (SLPEL) for pediatric inguinal hernia has gained popularity worldwide. However, complications associated with extraperitoneal knotting are not rare. This study evaluated the effectiveness of a modified SLPEL (M-SLPEL) to decrease adverse events associated with ligation knotting by comparing it with two other methods: classical SLPEL (C-SLPEL) and intracorporeal purse-string suturing (IPS). METHODS: A multicenter retrospective comparative study was conducted among 5523 pediatric inguinal hernia patients. Cases were divided into three groups according to the surgical procedure: the M-SLPEL, C-SLPEL, and IPS groups. Data describing the clinical characteristics, operative time, and complications were collected. RESULTS: All procedures were performed uneventfully. There were no significant differences in the age at operation (mean 2.62 ± 1.38 years). The operative time was shorter in the M-SLPEL group both for unilateral hernias (12.5 ± 1.8 min in C-SLPEL, 11.7 ± 1.3 min in M-SLPEL, and 17.6 ± 2.9 min in IPS) and for bilateral hernias (15.1 ± 2.1 min, 14.6 ± 1.7 min, and 23.9 ± 2.3 min, respectively). The overall incidence of adverse events in the inguinal region was 0% for M-SLPEL, 2.2% for C-SLPEL, and 0.5% for IPS. All patients were followed up for 12-93 months (mean 54 months). Recurrence occurred in 8 cases in the C-SLPEL group, 1 case in the M-SLPEL group, and 8 cases in the IPS group, with no significance between groups. No scrotal hematoma, testicular atrophy, or iatrogenic cryptorchidism occurred in any group. CONCLUSION: The M-SLPEL procedure has time-consumption efficiency equivalent to that of C-SLPEL and even fewer adverse events in the inguinal region than IPS and C-SLPEL.

[Willis covered stent for paraclinoid aneurysms:efficacy and mid-long-term follow-up results].

The clinical data and follow-up results of 27 paraspinoid aneurysms treated by Willis covered stent (WCS) in Department of Neurosurgery, Army Medical University from May 2014 to January 2021 were retrospectively analyzed. Among them, 17 cases (63.0%) were treated with WCS alone, and 10 cases (37.0%) were assisted with coiling embolization. During the follow-up, postoperative internal leakage occurred in 2 patients(7%), of which 1(type Ⅰ) wasself-healing and the other 1 (type Ⅲ) was cured by WCS implantation again. The remaining patients had no aneurysm recurrence, unobstructed parent artery, stent displacement and internal stenosis. 92.6% (25/27) of the improved mRS scores were good. WCS is a safe and effective method for the treatment of parabedinal aneurysms.

Exogenous citric acid enhances drought tolerance in tobacco (Nicotiana tabacum).

Organic acids play a pivotal role in improving plant response to long-term drought stress. External application of organic acids has been reported to improve drought resistance in several species. However, whether organic acids have similar effects in tobacco remains unknown. A screening study of the protective function of organic acids in tobacco and understanding the underlying molecular mechanism would be useful in developing a strategy for drought tolerance. Several physiological and molecular adaptations to drought including abscisic acid, stomatal closure, reactive oxygen species homeostasis, amino acid accumulation, and drought-responsive gene expression were observed by exogenous citric acid in tobacco plants. Exogenous application of 50 mm citric acid to tobacco plants resulted in higher chlorophyll content, net photosynthesis, relative water content, abscisic acid content and lower stomatal conductance, transpiration and water loss under drought conditions. Moreover, reactive oxygen species homeostasis was better maintained through increasing activity of antioxidant enzymes and decreasing hydrogen peroxide content after citric acid pretreatment under drought. Amino acids involved in the TCA cycle accumulated after external application of citric acid under drought stress. Furthermore, several drought stress-responsive genes also dramatically changed after application of citric acid. These data support the idea that external application of citric acid enhances drought resistance by affecting physiological and molecular regulation in tobacco. This study provides clear insights into mechanistic details of regulation of amino acid and stress-responsive gene expression by citric acid in tobacco in response to drought, which is promising for minimizing growth inhibition in agricultural fields.

Belantamab mafodotin for the treatment of multiple myeloma.

Multiple myeloma is the second most common hematologic malignancy worldwide. Despite the growing number of available therapeutic options and advances in the treatment since the 2000s, relapse of multiple myeloma is inevitable. Currently, the main therapeutic agents for multiple myeloma treatment include proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies and others. Patients who relapse or are refractory to the above-mentioned treatments have poor prognosis. B-cell maturation antigen (BCMA) is a cell-surface receptor which is expressed on the membrane of multiple myeloma cells, but absent on naive and memory B cells, making it an ideal target for multiple myeloma treatment. Belantamab mafodotin (GSK-2857916) is a first-in-class BCMA antibody-drug conjugate with an overall response rate of 32% in the phase II clinical trial DREAMM-2, which is a phase II study designed to investigate the efficacy and safety of belantamab mafodotin in relapsed/refractory patients with multiple myeloma. In August 2020, based on the results of this pivotal DREAMM-2 study, the U.S. Food and Drug Administration (FDA) approved belantamab mafodotin as a monotherapy for relapsed/refractory multiple myeloma. Thereafter, the European Medicines Agency (EMA) also approved this indication. Although belantamab mafodotin has demonstrated single-agent activity in relapsed/refractory multiple myeloma, further studies to evaluate its efficacy and its combinational use with other drugs are necessary and ongoing.

Tafasitamab for refractory/relapsed diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a common lymphoproliferative and invasive disease. The current first-line regimen for the treatment of DLBCL is R-CHOP, which is the combination of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. R-CHOP has significantly improved the outcome of DLBCL in the last decades. However, 30-40% of patients fail the therapy with R-CHOP. Salvage chemotherapy for relapsed/refractory DLBCL (R/R DLBCL) is extremely challenging, especially in elderly patients. In July 2020, a new monoclonal antibody, tafasitamab, was approved by the Food and Drug Administration (FDA) of the United States for the treatment of DLBCL. Tafasitamab is an anti-CD19 monoclonal antibody which is Fc-enhanced and humanized. CD19 is typically expressed in the developing B cells in non-Hodgkin's lymphomas. Tafasitamab has been proven to be a safe and valid treatment and recommended to be used in combination with lenalidomide in adults with R/R DLBCL who are ineligible for autologous stem cell transplantation (ASCT). This article evaluates the pharmacodynamics, pharmacokinetics, mechanism of action and the clinical application of tafasitamab in the treatment of DLBCL, particularly in R/R DLBCL. The advantages and disadvantages of using tafasitamab and chimeric antigen receptor T cells (CAR-T cells) targeting CD19 are also discussed.

[Establishment and validation of prognosis predictive model using m6A RNA methylation regulators in children acute myeloid leukemia].

Objective: To figure out the association between the expression of m6A RNA methylation regulators and the prognosis of children AML, and provide genetic markers for monitoring the progression and recurrence of AML. Methods: Twenty two m6A RNA methylation regulators were firstly analyzed using the data from Therapeutically Applicable Research To Generate Effective Treatments(TARGET) database and The Genotype-Tissue Expression(GTEx) database, Wilcoxon rank test was performed to analyze the differentially expression of m6A RNA methylation regulators between the AML and normal tissue, 296 AML children were divided into training cohort and validation cohort by simple random sampling method, Lasso regression was used to screen out the risk factors and the multivariate Cox regression was applied for establishing prognosis predicting model in training cohort. Kaplan-Meier survival curve, time-dependent ROC curve and multivariate Cox regression were used to estimate the efficiency of risk score calculated by predictive model in validation cohort. Results: Twenty one m6A genes were up regulated in AML compared to Normal patients. Five m6A RNA methylation regulators(ZC3H13, YTHDC2, HNRNPA2B1, METTL3, METTL5) were included in final predicting model. Risk score could independently predict the survival of AML patients in training cohort(HR:2.72, 95%CI: 1.54-4.81, P=0.000 6) and validation cohort(HR:2.01, 95%CI:1.14-3.50, P=0.016). Low-risk patients had better prognoses than high-risk patients both in training cohort(P=0.001 9) and validation cohort(P=0.023). Conclusion: This prognosis predicting model constructed by m6A RNA methylation regulators could independently predict the survival prognosis in AML children, and should be helpful for clinical therapy.

[A multicenter retrospective study on the etiology of necrotizing pneumonia in children].

Objective: To investigate the etiology of necrotizing pneumonia (NP) in children and the clinical characteristics of NP caused by different pathogens in China. Methods: A retrospective, case-control study was performed in children with NP who were admitted to 13 hospitals in China from January 2008 to December 2019. The demographic and clinical information, laboratory data, etiological and radiological findings were analyzed. The data were divided into three groups based on the following years: 2008-2011, 2012-2015 and 2016-2019, and the distribution characteristics of the pathogens in different period were compared. Meanwhile, the pathogens of pediatric NP in the southern and northern China were compared. And the clinical characteristics of the Mycoplasma pneumoniae (MP) NP and the bacterial NP were also compared. T-test or Mann-Whitney nonparametric test was used for comparison of numerical variables, and χ2 test was used for categorical variables. Results: A total of 494 children with NP were enrolled, the median ages were 4.7 (0.1-15.3) years, including 272 boys and 222 girls. Among these patients, pathogens were identified in 347 cases and the pathogen was unclear in the remaining 147 cases. The main pathogens were MP (238 cases), Streptococcus pneumoniae (SP) (61 cases), Staphylococcus aureus (SA) (51 cases), Pseudomonas aeruginosa (13 cases), Haemophilus influenzae (10 cases), adenovirus (10 cases), and influenza virus A (7 cases), respectively. MP was the most common pathogen in all three periods and the proportion increased yearly. The proportion of MP in 2016-2019 was significantly higher than that in 2012-2015 (52.1% (197/378) vs. 36.8% (32/87), χ2=6.654, P=0.010), while there was no significant difference in the proportion of MP in 2012-2015 and that in 2008-2011 (36.8% (32/87) vs. 31.0% (9/29), χ²=0.314, P=0.575).Regarding the regional distribution, 342 cases were in the southern China and 152 in the northern China. Also, MP was the most common pathogen in both regions, but the proportion of MP was higher and the proportion of SP was lower in the north than those in the south (60.5% (92/152) vs. 42.7% (146/342), χ2=13.409, P<0.010; 7.9% (12/152) vs. 14.3% (49/342), χ2=4.023, P=0.045). Comparing the clinical characteristics of different pathogens, we found that fever and cough were the common symptoms in both single MP and single bacterial groups, but chest pain was more common (17.0% (34/200) vs. 6.1% (6/98), χ2=6.697, P=0.010) while shortness of breath and wheezing were less common in MP group (16.0% (32/200) vs. 60.2% (59/98), χ2=60.688, P<0.01; 4.5% (9/200) vs. 21.4% (21/98), χ2=20.819, P<0.01, respectively). The white blood cell count, C-reactive protein and procalcitonin in the bacterial group were significantly higher than those in the MP group (14.7 (1.0-67.1)×109/L vs. 10.5 (2.5-32.2)×109/L, 122.5 (0.5-277.3) mg/L vs. 51.4 (0.5-200.0) g/L, 2.13 (0.05-100.00) µg/L vs. 0.24 (0.01-18.85) µg/L, Z=-3.719, -5.901 and -7.765, all P<0.01). Conclusions: The prevalence of pediatric NP in China shows an increasing trend during the past years. MP, SP and SA are the main pathogens of NP, and the most common clinical symptoms are fever and cough. The WBC count, C-reactive protein and procalcitonin in bacterial NP are significantly higher than those caused by MP.

[The relationship between premature atrial complexes and recurrence of atrial fibrillation: a meta-analysis].

Objective: To explore the relationship between premature atrial complexes (PACs) and recurrence of atrial fibrillation (AF). Methods: Published literature was searched in PubMed, Embase, Web of Science, Cochrane, Weipu, China national knowledge infrastructure, Wanfang and China Biology Medicine disc up to 25 March 2020. RevMan5.3 software was used to analyzed the data and publication bias was performed by Stata 15.1. Results: A total of 8 studies were identified, including 1 252 AF patients with a mean age of 61.67 years, and male patients accounted for 70.6%. During follow-up, AF recurred in 425 cases. Meta-analysis showed that frequent PACs was an independent risk factor for recurrence of AF (HR=2.64, 95%CI:1.40-4.97). Subgroup analyses showed that PACs not only increasedthe risk of recurrence of AF after electrical cardioversion (HR=2.38, 95%CI:1.25-4.51), but also significantly increased the risk of recurrence of AF after catheter ablation cardioversion (HR=2.90, 95%CI:1.11-7.60). Conclusions: PACs is significantly associated with AF recurrence.

Combination treatment of copanlisib and gemcitabine in relapsed/refractory PTCL (COSMOS): an open-label phase I/II trial.

BACKGROUND: Current treatment options for peripheral T-cell lymphomas (PTCLs) in the relapsed/refractory setting are limited and demonstrate modest response rates with rare achievement of complete response (CR). PATIENTS AND METHODS: This phase I/II study (NCT03052933) investigated the safety and efficacy of copanlisib, a phosphatidylinositol 3-kinase-α/-δ inhibitor, in combination with gemcitabine in 28 patients with relapsed/refractory PTCL. Patients received escalating doses of intravenous copanlisib on days 1, 8, and 15, administered concomitantly with fixed-dose gemcitabine (1000 mg/m2 on days 1 and 8) in 28-day cycles. RESULTS: Dose-limiting toxicity was not observed in the dose-escalation phase and 60 mg copanlisib was selected for phase II evaluation. Twenty-five patients were enrolled in phase II of the study. Frequent grade ≥3 adverse events (AEs) included transient hyperglycemia (57%), neutropenia (45%), thrombocytopenia, (37%), and transient hypertension (19%). However, AEs were manageable, and none were fatal. The overall response rate was 72% with a CR rate of 32%. Median duration of response was 8.2 months, progression-free survival was 6.9 months, and median overall survival was not reached. Combination treatment produced a greater CR rate in patients with angioimmunoblastic T-cell lymphoma than those with PTCL-not otherwise specified (55.6% versus 15.4%, respectively, P = 0.074) and progression-free survival was significantly longer (13.0 versus 5.1 months, respectively, P = 0.024). In an exploratory gene mutation analysis of 24 tumor samples, TSC2 mutation was present in 25% of patients and occurred exclusively in responders. CONCLUSION: The combination of copanlisib and gemcitabine is a safe and effective treatment option in relapsed/refractory PTCLs and represents an important new option for therapy in this rare group of patients.

Long-term clinical outcomes of endoscopic submucosal dissection for colorectal neoplasia with or without the hybrid technique.

AIM: The main aim of this study was to compare the long-term outcome of a conventional colorectal endoscopic submucosal dissection (ESD) in which submucosal dissection was continued throughout until the completion of resection (ESD-T) to hybrid endoscopic submucosal dissection (ESD-H) in the colorectum. METHOD: Medical records of 836 colorectal neoplasia patients treated by ESD-T or ESD-H were reviewed. ESD-H was defined as colorectal ESD with additional snaring in the final stage of the procedure. Primary outcomes were the overall and metastatic recurrence rates. Secondary outcomes were short-term outcomes such as the en bloc resection rate, procedure time and adverse events. RESULTS: The overall recurrence rate was higher in the ESD-H than in the ESD-T group (5.7% vs 0.7%, P = 0.001). The metastatic recurrence rate showed no significant difference between these groups (1.4% vs 1.4%, P = 1.000). Multivariate analysis revealed that a failed en bloc resection (hazard ratio 24.097; 95% CI 5.446-106.237; P < 0.001) and larger tumour size (hazard ratio 1.042; 95% CI 1.014-1.070; P = 0.003) were independently associated with overall recurrence. The ESD-H group showed a lower en bloc resection rate (56.8% vs 96.5%, P < 0.001), shorter procedure time (45.6 vs 54.3 min, P < 0.001) and higher perforation rate (10.3% vs 6.0%, P = 0.029). CONCLUSION: Although long-term outcomes in terms of overall recurrence are inferior following ESD-H, a failed en bloc resection and large tumour size are the only independent risk factors for recurrence. Further investigations are warranted to improve the long-term outcomes of ESD-H.

Association of low skeletal muscle mass with the presence of advanced colorectal neoplasm: integrative analysis using three skeletal muscle mass indices.

AIM: This study aimed to evaluate an association between colorectal neoplasm (CRN) and skeletal muscle mass using three widely accepted skeletal muscle mass indices (SMIs) in a large population at average risk. METHOD: We performed a cross-sectional study using a screening colonoscopy database of 33 958 asymptomatic subjects aged 40-75 years. Appendicular skeletal muscle mass (ASM) was measured using a bioelectrical impedance analyser. ASM adjusted for height squared (ASM/ht2 ), weight (ASM/wt) and body mass index (ASM/BMI) were used as indices for muscle mass. Logistic regression models were used to evaluate the association between SMIs and CRN. RESULTS: In a multivariable-adjusted model, the risk of an advanced CRN increased linearly with decreasing quartiles for all three SMIs. The adjusted odds ratios (ORs) for advanced CRN in quartiles 1, 2 and 3 of ASM/wt compared with that in quartile 4 were 1.279, 1.196 and 1.179, respectively (Ptrend  = 0.017); for ASM/BMI, ORs were 1.307, 1.144 and 1.091, respectively (Ptrend  = 0.002); and for ASM/ht2 , ORs were 1.342, 1.169 and 1.062, respectively (Ptrend  = 0.002). The risk of distally located advanced CRN was higher in quartile 1 than in quartile 4 for all three SMIs (ASM/wt, OR = 1.356; ASM/BMI, OR = 1.383; ASM/ht2 , OR = 1.430). CONCLUSION: Our study demonstrated that low skeletal muscle mass was consistently associated with the presence of advanced CRN in a population at average risk regardless of the operational definition of the SMI, and it was particularly associated with distal advanced CRN.

[Comparison of nucleic acid detection methods in pharyngeal swabs of Mycoplasma pneumoniae infection in children].

Objective: To explore the value of nucleic acid detection methods in pharyngeal swabs in the etiological diagnosis of Mycoplasma pneumoniae (MP) infection in children. Methods: Four hundred and fifty-four (male 210, female 244) children with pneumonia in Department of Pulmonology, Children's Hospital of Zhejiang University School of Medicine were enrolled from July, 2018 to October, 2018. Pharyngeal swabs and venous blood were obtained on the first or the second day after hospitalization. Fluorescence detection quantitative amplification of DNA, thermostatic amplification of RNA, MP culture and MP-IgM were used to detect MP simultaneously. MP infection is diagnosed if MP culture is positive or the two of the other three methods are positive. Pharyngeal swabs were acquired and detected using fluorescence quantitative amplification of DNA, thermostatic amplification of RNA and MP culture again for children with confirmed MP infection before discharge. The detection rates and quantitative changes of the three methods were compared, and χ(2) test was used for comparison among groups. Results: A total of 454 hospitalized children with pneumonia were included in this study. The detection rates of fluorescence quantitative amplification of DNA, thermostatic amplification of RNA, MP culture and MP-IgM IgM were 43.6% (198/454), 43.2% (196/454), 40.0% (180/454) and 30.6% (139/454) respectively. The difference of detection rates of the four methods was statistically significant (χ(2)=20.8, P<0.05),but no significant difference between the detection rates of fluorescence quantitative amplification of DNA and thermostatic amplification of RNA was found (χ(2)=0.018, P=0.900). They both had higher detection rates than MP-IgM or MP culture. MP infection is diagnosed if MP culture is positive or the two of the other three methods are positive, and two hundred and nine children were diagnosed as MP infection. In the second test of MP infection in 209 children before discharge, the positive rate of MP culture was 67.5% (141/209), with 39.4% (13/33) changed from negative to positive, and 27.3% (48/176) changed from positive to negative. The positive rate of thermostatic amplification of RNA was 82.3% (172/209), with 16.2% (31/191) turned from positive to negative, and 66.7% (12/18) turned from negative to positive. The positive rate of fluorescence quantitative amplification of DNA was 67.0% (140/209), with 52.9% (18/34) cases changed from negative to positive, and 30.3% (53/175) cases changed from positive to negative. MP-DNA load decreased in 141 cases (67.5%) and increased in 68 cases (32.5%) in the second test among the positive samples tested by fluorescence quantitative amplification of DNA. The detection rates of the four methods in the non-severe group and the severe group were similar, and the differences among the groups were not statistically significant (all P>0.05). In the second test, the proportion of changing from negative to positive in the severe group was higher than that in the non-severe group, but only the difference in the thermostatic amplification of RNA was statistically significant (P=0.038) and the cases of changing from negative to positive of thermostatic amplification of RNA in the severe group and non-severe group are 7 and 5 respectively. Conclusions: The methods of pharyngeal swab nucleic acid detection have high sensitivity and application value in the etiological diagnosis of acute MP infection in children. The results of fluorescence quantitative amplification of DNA and thermostatic amplification of RNA are highly consistent, and they are both more advantageous than MP-IgM. Repeated testing in the acute phase is helpful to find MP infection children whose first test is negative. The load of MP-DNA did not decrease in some children in the acute stage after antibiotic treatment.

Prognostic model for identifying candidates for hepatectomy among patients with hepatocellular carcinoma and hepatic vein invasion.

BACKGROUND: Hepatic vein tumour thrombus (HVTT) is a major determinant of survival outcomes for patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT model was established to predict the prognosis of patients with HCC and HVTT after liver resection, in order to identify optimal candidates for liver resection. METHODS: Patients with HCC and HVTT from 15 hospitals in China were included. The EHBH-HVTT model with contour plot was developed using a non-linear model in the training cohort, and subsequently validated in internal and external cohorts. RESULTS: Of 850 patients who met the inclusion criteria, there were 292 patients who had liver resection and 198 who did not in the training cohort, and 124 and 236 in the internal and external validation cohorts respectively. Contour plots for the EHBH-HVTT model were established to predict overall survival (OS) rates of patients visually, based on tumour diameter, number of tumours and portal vein tumour thrombus. This differentiated patients into low- and high-risk groups with distinct long-term prognoses in the liver resection cohort (median OS 34·7 versus 12·0 months; P < 0·001), internal validation cohort (32·8 versus 10·4 months; P = 0·002) and external validation cohort (15·2 versus 6·5 months; P = 0·006). On subgroup analysis, the model showed the same efficacy in differentiating patients with HVTT in peripheral and major hepatic veins, the inferior vena cava, or in patients with coexisting portal vein tumour thrombus. CONCLUSION: The EHBH-HVTT model was accurate in predicting prognosis in patients with HCC and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including tumour thrombus in the inferior vena cava, or coexisting portal vein tumour thrombus.

ANTECEDENTES: La trombosis tumoral de la vena hepática (hepatic vein tumour thrombus, HVTT) es un determinante importante de los resultados de supervivencia en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC). Se desarrolló el modelo llamado Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT para predecir el pronóstico de los pacientes con HCC y HVTT después de la resección hepática (liver resection, LR), con el fin de identificar los candidatos óptimos para LR entre estos pacientes. MÉTODOS: Se incluyeron pacientes con HCC y HVTT de 15 hospitales en China. El modelo EHBH-HVTT con gráfico de contorno se desarrolló utilizando un modelo no lineal en la cohorte de entrenamiento, siendo posteriormente validado en cohortes internas y externas. RESULTADOS: De 850 pacientes que cumplieron con los criterios de inclusión, hubo 292 pacientes en el grupo LR y 198 pacientes en el grupo no LR en la cohorte de entrenamiento, y 124 y 236 en las cohortes de validación interna y externa. Los gráficos de contorno del modelo EHBH-HVTT se establecieron para predecir visualmente las tasas de supervivencia global (overall survival, OS) de los pacientes, en función del diámetro del tumor, número de tumores y del trombo tumoral de la vena porta (portal vein tumour thrombus, PVTT). Esto diferenciaba a los pacientes en los grupos de alto y bajo riesgo, con distinto pronóstico a largo plazo en las 3 cohortes (34,7 versus 12,0 meses, 32,8 versus 10,4 meses y 15,2 versus 6,5 meses, P < 0,001). En el análisis de subgrupos, el modelo mostró la misma eficacia en la diferenciación de pacientes con HVTT, con trombo tumoral en la vena cava inferior (inferior vena cava tumour thrombus, IVCTT) o en pacientes con PVTT coexistente. CONCLUSIÓN: El modelo EHBH-HVTT fue preciso para la predicción del pronóstico en pacientes con HCC y HVTT después de la LR. Identificó candidatos óptimos para LR en pacientes con HCC y HVTT, incluyendo IVCTT o PVTT coexistente.

[Comparative analysis of clinical characteristics and prognosis between bacterial necrotizing pneumonia and Mycoplasma pneumoniae necrotizing pneumonia in children].

Objective: To compare the characteristics of Mycoplasma pneumoniae necrotizing pneumonia (MPNP) and bacterial necrotizing pneumonia (BNP), and explore the biomarkers for differentiation of MPNP from BNP. Methods: A retrospective, observational study of 52 necrotizing pneumonia (NP) cases who were hospitalized in our hospital from January 2008 to December 2017 was conducted. According to the pathogen causing NP, patients were divided into two groups, BNP and MPNP, and the clinical manifestations, laboratory data, imaging findings, hospital course and prognosis between these groups were analyzed. Results: This study enrolled 19 boys and 33 girls, and the median ages of patients were 4.4 (0.1-13.8) years old. Of the totally of 52 NP patients, 19 were in the BNP group (9 boys and 10 girls), 33 were in the MPNP group (10 boys and 23 girls). The mean age of MPNP patients was much older than that of BNP patients (5.2 (2.3-13.2) years vs. 1.8 (0.1-13.8) years, Z=-0.128, P<0.01). The number of patients with tachypnea and pleural effusion septation were significantly higher in BNP patients than those in MPNP patients (15 cases vs. 4 cases, χ(2)=23.222, P<0.01; 14 cases vs. 1 case, χ(2)=29.326, P<0.01), which more needed to oxygentherapy (18 cases vs. 12 cases, χ(2)=16.833, P<0.01) and undergo chest drainage (9 cases vs. 4 cases, χ(2)=5.829, P=0.022); while the number of patients required bronchoalveolar lavage was higher in MPNP patients than that in BNP patients (5 cases vs. 32 cases, χ(2)=29.326, P<0.01). The values of white blood cell (WBC) (23.2 (5.2-67.1)×10(9)/L vs. 9.7 (6.3-18.7)×10(9)/L, Z=-4.855, P<0.01), procalcitonin (PCT) (3.69 (0.23-90.15) mg/L vs. 0.28 (0.02-1.44) mg/L, Z=-3.207, P=0.001), C reactive protein (CRP) (160 (94-220) mg/L vs. 90 (5-134) mg/L, Z=-4.337, P<0.01), interleukin (IL)-10 (11.7 (4.2-401.5) ng/L vs. 4.8 (2.0-23.4) ng/L, Z=-2.278, P=0.023), pleural fluid cell count (5 200 (120-50 000)×10(6)/L vs. 790 (68-6 920)×10(6)/L, Z=-3.125, P=0.002), pleural fluid lactic dehydrogenase (LDH) (3 990 (589-29 382) U/L vs. 2 211 (673-3 993) U/L, Z=-2.488, P=0.013) in BNP group were significantly higher than those in MPNP group; while the values of pleural fluid glucose(0.43 (0.03-18.00) mmol/L vs. 5.95 (4.27-7.87) mmol/L, Z=-2.795, P=0.005), serum tumor necrosis factor (TNF)-α (2.3 (1.0-2.8) ng/L vs. 2.6 (1.3-109.2) ng/L, Z=-2.113, P=0.035) and interferon (IFN)-γ (4.8 (2.6-7.7) ng/L vs. 11.9 (2.9-154.6) ng/L, Z=-2.455, P=0.014) were lower in BNP group than those in MPNP group. Meanwhile, the mean time from the onset of symptoms to the discovery of necrotic lesions was longer in MPNP group than that in BNP group ((20.6±6.4) days vs. (14.6±6.2) days, t=3.029, P=0.004). After treatments, all patients were discharged without death, WBC and PCT recovered more quickly in MPNP group than those in BNP group (12 (0-24) days vs. 0 (0-23) days, Z=-4.484, P<0.01; 10 (5-15) days vs. 0 (0-23) days, Z=-3.244, P=0.001). As to prognosis, 34 cases were followed up, and the results showed that patients recovered without surgical intervention, and chest lesions were resolved within 3.0 (1.0-8.0) months, and the time to necrosis disappearance was similar in the BNP group and MPNP greup (3.0 (1.0-8.0) months vs. 3.0 (1.0-8.0) months, Z=-0.128, P=0.001). In receiver operator characteristic curve analysis, the cut-off values for the age, WBC, CRP, PCT, pleural fluid cell count and pleural fluid glucose were set at 2.4 years of age, 17.2×10(9)/L, 157 mg/L, 1.505 mg/L, 2 630×10(6)/L and 3.73 mmol/L, respectively. Conclusions: NP is found to be severe and prolonged, yet, reversible through proper therapy, such as rational antibiotics application. The age, WBC, CRP, PCT, pleural fluid cell count and pleural fluid glucose could be used as biomarkers to differentiate MPNP from BNP in children.

Gender difference in clinical and genetic characteristics of Brugada syndrome: SADS-TW BrS registry.

BACKGROUND: Brugada syndrome (BrS) is a heritable sudden cardiac death (SCD) disease with male predominance. Information on gender difference of BrS remains scarce. AIM: To investigate the gender difference of BrS in Han Chinese. DESIGN: We consecutively enrolled 169 BrS patients (153 males and 16 females) from Han Chinese in Taiwan from 1998 to 2017. METHODS: Clinical characteristics, electrocardiographic parameters and SCN5A mutation status were compared between genders. RESULTS: The percentage of family history of SCD in females was slightly higher (31.3% vs. 15%, P = 0.15). Females exhibited longer QTc (457.8 ± 33.0 vs. 429.5 ± 42.1 ms, P < 0.01). Regarding cumulative event occurrence by age, Mantel-Cox test showed females had earlier age of onset of first cardiac events (SCD or syncope) than males (P = 0.049), which was mainly attributed to syncope (P < 0.01). Males with SCD exhibited longer QRS duration (114.2 ± 26.8 vs. 104.8 ± 15.3 ms, P = 0.02) and QTc (442.5 ± 57.4 vs. 422.9 ± 28.8 ms, P = 0.02). Males with syncope exhibited longer PR interval (181.2 ± 33.7 vs. 165.7 ± 27.1 ms, P = 0.01), whereas females with SCD or syncope had a trend towards slower heart rates (69.1 ± 9.6 vs. 82.2 ± 16.3 bpm, P = 0.10) than female with no or mild symptoms. There was no difference in the percentage of SCN5A mutation between genders. CONCLUSION: Gender difference is present in BrS. Females have longer QTc and suffer from syncope earlier than males. Risk of SCD in males is associated with boarder QRS complex and longer QTc, whereas risk of syncope is associated with longer PR interval in males and slower heart rate in females.

Predictive value of a fragmented QRS complex in diagnosing patients with myocardial ischemia.

BACKGROUND: A fragmented QRS complex (fQRS) is caused by conduction abnormalities of the ventricle secondary to myocardial ischemia and/or scar in patients with myocardial infarction. However, the implications of the fQRS in the development of coronary artery disease with myocardial ischemia in those without a scar remain unknown. METHODS: We studied electrocardiograms (ECGs) obtained from 150 patients (60.5 ± 8.5 years, 102 men) with myocardial ischemia, which was confirmed by performing both, a nuclear exercise stress test and coronary angiography. We also studied ECGs obtained from 601 patients (58.5 ± 10.0 years, 315 men) who showed a negative nuclear exercise stress test (control group). Patients in whom the nuclear exercise stress test showed a myocardial scar were excluded. RESULTS: An fQRS was more commonly observed in patients with myocardial ischemia (n = 48, 32.0%) than in the control group (n = 133, 22.1%) (P = 0.011). The sensitivity, specificity, positive, and negative predictive values of fQRS in diagnosing myocardial ischemia were 32.0, 77.9, 26.5, and 82.1%, respectively. The fQRS (odds ratio 1.580, 95% confidence interval 1.020-2.446, P = 0.040) was an independent predictor of myocardial ischemia after adjusting for age, sex, current smoking habits, ST-T changes on ECG, as well as histories of hypertension, diabetes, and dyslipidemia. Moreover, the fQRS showed an incremental prognostic value over conventional risk factors (χ2 = 5, P = 0.032) and over a combination of conventional factors and ST-T changes (χ2 = 9, P = 0.014). CONCLUSIONS: The fQRS is a moderately sensitive and independent predictor of myocardial ischemia.

[The value of MRI in early diagnosis of dysbaric osteonecrosis].

Objective: To investigate the value of MRI in the early diagnosis of diagnosis of dysbaric osteonecrosis. Methods: Labor hygiene investigation and occupation health were examined on 52 high pressure operating personnel, were selected for the examination of both shoulders, hips and knees with X-ray and CT scan. Results: The cystic sign in dysbaric osteonecrosis as an important imaging feature, which perform in the MRI examination for T1W I sequence showed low or slightly low signal and T2W I sequence showed high signal, and X-ray and CT have a lower detection rate than MRI. The Kappa consistency test showed a high consistency with the two methods. At the same time MRI examination also can discover the bone marrow cavity necrosis early pathological change. Conclusion: MRI is an effective method for the diagnosis of early dysbaric osteonecrosis, which can improve the early diagnosis rate of dysbaric osteonecrosis.