Suspension microarray-based comparison of oropharyngeal swab and bronchoalveolar lavage fluid for pathogen identification in young children hospitalized with respiratory tract infection.

BACKGROUND: Respiratory tract infection (RTI) in young children is a leading cause of morbidity and hospitalization worldwide. There are few studies assessing the performance for bronchoalveolar lavage fluid (BALF) versus oropharyngeal swab (OPS) specimens in microbiological findings for children with RTI. The primary purpose of this study was to compare the detection rates of OPS and paired BALF in detecting key respiratory pathogens using suspension microarray. METHODS: We collected paired OPS and BALF specimens from 76 hospitalized children with respiratory illness. The samples were tested simultaneously for 8 respiratory viruses and 5 bacteria by suspension microarray. RESULTS: Of 76 paired specimens, 62 patients (81.6%) had at least one pathogen. BALF and OPS identified respiratory pathogen infections in 57 (75%) and 49 (64.5%) patients, respectively (P > 0.05). The etiology analysis revealed that viruses were responsible for 53.7% of the patients, whereas bacteria accounted for 32.9% and Mycoplasma pneumoniae for 13.4%. The leading 5 pathogens identified were respiratory syncytial virus, Streptococcus pneumoniaee, Haemophilus influenzae, Mycoplasma pneumoniae and adenovirus, and they accounted for 74.2% of etiological fraction. For detection of any pathogen, the overall detection rate of BALF (81%) was marginally higher than that (69%) of OPS (p = 0.046). The differences in the frequency distribution and sensitivity for most pathogens detected by two sampling methods were not statistically significant. CONCLUSIONS: In this study, BALF and OPS had similar microbiological yields. Our results indicated the clinical value of OPS testing in pediatric patients with respiratory illness.

Suspension array-based deafness genetic screening in 53,033 Chinese newborns identifies high prevalence of 109 G>A in GJB2.

OBJECTIVES: More than 50% of congenital hearing loss is attributed to genetic factors. Data of gene mutation associated with hearing loss from large population studies in Chinese population are scarce. In this study, we conducted a comprehensive newborn genetic screening in China to establish the carrier frequency and mutation spectrum of deafness-associated genes. METHODS: A total of 53,033 newborns were screened for hearing defects associated mutations. Twenty hot spot mutations in GJB2, GJB3, SLC26A4 and mitochondria12S rRNA were examined using suspension array analysis. RESULTS: 14,185 newborns (26.75%) were identified with at least one mutated allele. 872 (1.64%) neonates carried homozygous mutations including 112 (0.21%) mitochondrial DNA homoplasmy, 228 (0.43%) were compound heterozygotes, and 11,985 (22.59%) were heterozygotes including 11 (0.02%) mitochondrial DNA heteroplasmy. Top five mutations included 109 G > A, 235 delC, 299-300 delAT in GJB2, IVS7-2 A > G in SLC26A4 and 1555 A > G in mitochondria12S rRNA. Notably, a total of 10,995 neonates (20.73%) carried 109 G > A in GJB2. Moreover, the allele frequencies of 109 G > A were detected 11.61% in Guangdong, 10.44% in Sichuan and 2.88% in Shandong, respectively, a significant difference in prevalence among these geographic regions (p<0.01). In addition, the high frequency of 109 G > A in GJB2 was confirmed by a TaqMan probe-based qPCR assay. Very recently, the ClinGen Hearing Loss Expert Panel reached a consensus and confirmed its pathogenic role in hearing impairment. CONCLUSION: We delineated the mutation profile of common deafness-causing genes in the Chinese population and highlighted the high prevalence of 109 G > A pathogenic mutation. Our study may facilitate early diagnosis/intervention and genetic counseling for hearing impairment in clinical practice.

Lymphopenia in Esophageal Squamous Cell Carcinoma: Relationship to Malnutrition, Various Disease Parameters, and Response to Concurrent Chemoradiotherapy.

BACKGROUND: Lymphopenia occurs commonly in esophageal squamous cell carcinoma (ESCC) and may influence treatment outcomes. We aimed to examine its association with treatment response and tumor progression in patients with locally advanced ESCC treated with concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: A total of 286 patients with stage II-IVa ESCC treated with CCRT between 2015 and 2017 were analyzed. Total lymphocyte counts were assessed at baseline, weekly, and 4 weeks after CCRT. Pretreatment lymphopenia was defined as total lymphocyte count <1,000 cells per mm3 at diagnosis, and treatment-related lymphopenia was defined as total lymphocyte count <200 cells per mm3 with 6 weeks after starting CCRT. Univariate and multivariate logistic regression methods were used to analyze factors associated treatment-related lymphopenia and treatment response. RESULTS: Lymphopenia was observed in 44 patients (15.4%) at initial diagnosis. Pretreatment lymphopenia was significantly associated with greater tumor length, worse T status, body mass index ≤18.5 kg/m2, and weight loss ≥3 kg in the previous 3 months. Six weeks after starting CCRT, 89 patients (31%) developed treatment-related lymphopenia. Tumor progression and cancer-related death were more frequently observed in treatment-related lymphopenia group than those without (76.4% vs. 52.8% and 58.4% vs. 39.6%). A complete response (CR) was achieved in 62 patients (21.7%). In multivariate analysis, treatment-related lymphopenia was significantly associated with lack of clinical CR, and older age, lower tumor location, greater tumor length, and larger planning target volume were independent predictors of treatment-related lymphopenia. CONCLUSION: Treatment-related lymphopenia during CCRT is an independent predictor for poor treatment response in ESCC. IMPLICATIONS FOR PRACTICE: A total of 286 patients with locally advanced esophageal squamous cell carcinoma were treated with concurrent chemoradiotherapy (CCRT), and treatment-related lymphopenia occurred in 31% of patients within 6 weeks from the start of CCRT. Treatment-related lymphopenia was significantly associated with lack of treatment response, and older age, lower tumor location, greater tumor length, and larger planning target volume were independent predictors of treatment-related lymphopenia. Lymphocyte count is an inexpensive biomarker that may be easily used by clinicians to identify patients who are most likely to benefit from CCRT.

Combined application of pharamcokinetic DCE-MRI and IVIM-DWI could improve detection efficiency in early diagnosis of ductal carcinoma in situ.

PURPOSE: Ductal carcinoma in situ (DCIS) is a precursor of invasive ductal breast carcinoma (IDC). This study aimed to use pharamcokinetic dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for the early diagnosis of DCIS. METHODS: Forty-seven patients, including 25 with DCIS (age: 28-70 yr, mean age: 48.7 yr) and 22 with benign disease (age: 25-67 yr, mean age: 43.1 yr) confirmed by pathology, underwent pharamcokinetic DCE-MRI and IVIM-DWI in this study. The quantitative parameters Ktrans , Kep , Ve , Vp , and D, f, D* were obtained by processing of DCE-MRI and IVIM-DWI images with Omni-Kinetics and MITK-Diffusion softwares, respectively. Parameters were analyzed statistically using GraphPad Prism and MedCalc softwares. RESULTS: All low-grade DCIS lesions demonstrated mass enhancement with clear boundaries, while most middle-grade and high-grade DCIS lesions showed non-mass-like enhancement (NMLE). DCIS lesions were significantly different from benign lesions in terms of Ktrans , Kep , and D (t = 5.959, P < 0.0001; t = 5.679, P < 0.0001; and t = 5.629, P < 0.0001, respectively). The AUC of Ktrans , Kep , D and the combined indicator of Ktrans , Kep, and D were 0.936, 0.902, 0.860, and 0.976, respectively. There was a significant difference in diagnostic efficacy only between D and the combined indicator (Z = 2.408, P = 0.016). CONCLUSION: DCE-MRI and IVIM-DWI could make for the early diagnosis of DCIS, and reduce the misdiagnosis of DCIS and over-treatment of benign lesions.

Comparison of the clinical application value of mo-targeted X-ray, color doppler ultrasound and MRI in preoperative comprehensive evaluation of breast cancer.

OBJECTIVE: To investigate the clinical application value of the Mo-targeted X-ray examination, color Doppler ultrasound and magnetic resonance imaging (MRI) in the diagnosis and preoperative comprehensive evaluation of breast cancer. METHODS: Among 170 breast cancer patients, they underwent Mo-targeted X-ray examination, color Doppler ultrasound and MRI before surgery to evaluate the lesions in breast, axillary lymph nodes and the availability of breast-conserving surgery. RESULTS: The detection rates using color Doppler ultrasound examination and MRI were higher than that in the Mo-targeted X-ray examination, which were 90%, 94% and 82%, respectively (P < 0.01 or 0.05). With the result of pathological examination as the golden criteria, we found that specificities of Mo-targeted X-ray examination, color Doppler ultrasound examination and MRI in evaluating the metastasis in axillary lymph nodes were similar (85.11%, 77.66% and 79.79%; P > 0.05). Before surgery, the sensitivities and accuracies of the color Doppler ultrasound examination and MRI were higher than those using the Mo-targeted X-ray examination, which were 73.21%, 82.14%, and 28.57%, 76.00%, 80.67% and 64.00% (P < 0.01 or 0.05). Before surgery, the accuracy rate of MRI in evaluating the breast-conserving surgery was higher than those of Mo-targeted X-ray examination and color Doppler ultrasound (92.00%, 83.33% and 84.67%; P < 0.05). CONCLUSION: Combined application of Mo-targeted X-ray examination, color Doppler ultrasound and MRI shows a higher accuracy in diagnosis of breast cancer and evaluation of axillary lymph node metastasis, which is conducive to the selection of surgical methods.