Prenatal diagnosis of a severe form of frontonasal dysplasia with severe limb anomalies, hydrocephaly, a hypoplastic corpus callosum, and a ventricular septal defect using 3D ultrasound: a case report and literature review.

BACKGROUND: Frontonasal dysplasia (FND) is a rare congenital anomaly resulting from the underdevelopment of the frontonasal process, and it can be syndromic or nonsyndromic. The typical features of FND include a deformed nose and ocular hypertelorism, which are sometimes associated with cleft lip and/or palate. Only approximately 10 cases of prenatally diagnosed nonsyndromic FND have been reported in the past 30 years. CASE PRESENTATION: A 33-year-old woman (G2P1) was referred to our center at 20 gestational weeks for bilateral hydrocephaly. We detected typical features of FND, including severe hypertelorism, median nasal bifidity, a minor cleft lip, and multiple limb anomalies using three-dimensional (3D) ultrasound. A hypoplastic corpus callosum, unilateral microtia, and a ventricular septal defect were also detected. Genetic testing, including karyotype analysis, copy number variation (CNV) analysis, trio-whole exome sequencing (trio-WES), and trio-whole-gene sequencing (trio-WGS), was performed; however, we did not find any de novo gene variants in the fetus as compared to the parents. Postmortem examination confirmed the prenatal diagnosis of FND. CONCLUSION: The present case expands the wide phenotypic spectrum of prenatal FND patients. 3D ultrasound is a useful tool for detecting facial and limb deformities.

Unfavourable treatment outcomes in tuberculosis patients with different vitamin D status and blood glucose levels in a programme setting in China.

OBJECTIVE: Tuberculosis (TB) treatment success rates are high in China, but there are still a considerable number of cases who have unfavourable treatment outcomes (UTO). We aimed to determine the proportion of TB patients with UTO and to assess whether baseline characteristics that included glycaemic status [normal fasting blood glucose (FBG), transient hyperglycaemia and diabetes mellitus (DM)] and vitamin D status were associated with UTO. METHOD: Prospective cohort study conducted between November 2015 and July 2016 at six clinics within routine TB services in Jilin province, where persons with TB were consecutively recruited. Data analysis was performed using the chi-squared test and multivariate logistic regression. RESULTS: Of the 306 recruited TB patients, 96 (31.4%) had smear-positive pulmonary TB, 187 (61.1%) had smear-negative pulmonary TB and 23 (7.5%) had extrapulmonary TB (EPTB). Of these, 95 (31.1%) had normal blood glucose, 83 (27.1%) had transient hyperglycaemia and 128 (41.8%) had DM. 227 (74.2%) patients had vitamin D deficiency/severe deficiency. There were 125 (40.8%) patients with UTO of whom the majority were lost to follow-up (57.6%) or not evaluated (28.8%). UTO was significantly associated with smear-negative pulmonary TB (P = 0.009), EPTB (P < 0.001) and DM (P = 0.007). CONCLUSION: The proportion of TB patients with UTO increased with smear-negative pulmonary TB, EPTB and DM. TB programmes need to pay more attention to these issues and ensure intensive patient support to those at risk and early detection of DM.

OBJECTIF: Les taux de succès du traitement de la tuberculose (TB) sont élevés en Chine, mais il existe encore un nombre considérable de cas avec des résultats de traitement défavorables (RTD). Nous avons cherché à déterminer la proportion de patients TB avec un RTD et d'évaluer si les caractéristiques de base comprenant le statut glycémique [glycémie normale à jeun (GJ), hyperglycémie transitoire et diabète sucré (DS)] et le statut en vitamine D étaient associés à un RTD. MÉTHODE: Etude de cohorte prospective réalisée entre novembre 2015 et juillet 2016 dans six cliniques des services anti-TB de routine de la province de Jilin, où des personnes atteintes de TB ont été recrutées consécutivement. L'analyse des données a été réalisée à l'aide du test du chi carré et de la régression logistique multivariée. RÉSULTATS: Sur 306 patients TB recrutés, 96 (31.4%) avaient une TB pulmonaire à frottis positif, 187 (61.1%) avaient une TB pulmonaire à frottis négatif et 23 (7.5%) avaient une TB extra pulmonaire (TBEP). Parmi ceux-ci, 95 (31.1%) avaient une glycémie normale, 83 (27.1%) avaient une hyperglycémie transitoire et 128 (41.8%) avaient un DS. 227 (74.2%) patients avaient une déficience/déficience sévère en vitamine D. Il y avait 125 (40.8%) patients avec un RTD dont la majorité (57.6%) ont été perdus de vue ou ont été non évalués (28.8%). Le RTD était significativement associé à la TB pulmonaire à frottis négatif (p = 0.009), la TBEP (P < 0.001) et le DS (P = 0.007). CONCLUSION: La proportion de patients TB avec un RTD augmentait avec la TB pulmonaire à frottis négatif, la TBEP et le DS. Les programmes anti-TB devraient accorder plus d'attention à ces problèmes et assurer un soutien intensif au patient pour les personnes à risque et une détection précoce du DS.

Evaluation of Hemodynamic Changes in Fetuses With Isolated Mild-to-Moderate Ventriculomegaly by Transabdominal Ultrasound.

OBJECTIVES: To investigate fetal hemodynamic alterations using transabdominal ultrasound in fetuses with isolated mild-to-moderate ventriculomegaly (VM). METHODS: Fetuses diagnosed with isolated mild-to-moderate VM by transabdominal ultrasound were evaluated for hemodynamic changes, including changes in fetal cardiac function, the umbilical artery, the ductus venosus, and the middle cerebral artery. The fetuses with isolated mild-to-moderate VM were divided into 2 groups, namely, before 32 weeks' gestation (20 weeks-31 weeks 6 days) and after 32 weeks' gestation (32-38 weeks), and matched to corresponding healthy control fetuses. RESULTS: The 53 fetuses with VM before 32 weeks had a longer mean isovolumetric relaxation time (IRT; mean ± SD, 42.9 ± 6.8 versus 40.4 ± 5.0 milliseconds; P < .05) and an apparently higher modified myocardial performance index 0.46 ± 0.06 versus 0.43 ± 0.05; P < .01) than the healthy control fetuses. The 43 fetuses with VM after 32 weeks had a significantly longer mean IRT (45.5 ± 6.7 versus 40.9 ± 7.2 milliseconds; P < .01) and a lower UA pulsatility index (0.81 ± 0.13 versus 0.89 ± 0.11; P < .01). The optimal cutoff levels for the IRT in the prediction of adverse perinatal outcomes were 40 and 43 milliseconds before and after 32 weeks, respectively (sensitivity, 100% versus 100%; specificity, 40.4% versus 50.0%; area under the curve, 0.601 versus 0.748; 95% confidence interval, 0.457-0.733 versus 0.590-0.869; P = .291 versus .005). CONCLUSIONS: Some fetuses with isolated mild-to-moderate VM may have impaired cardiac function, characterized by a higher modified myocardial performance index or longer IRT. This finding might be useful for improving fetal surveillance.

Quantitative diagnostic advantages of three-dimensional ultrasound volume imaging for fetal posterior fossa anomalies: Preliminary establishment of a prediction model.

OBJECTIVES: To quantitatively assess prenatal diagnostic performance of three-dimensional ultrasound (3D-US) for posterior fossa anomalies (PFA) and establish a preliminarily 3D-US prediction model. METHODS: Sixty singleton fetuses suspected of PFA by 2D-US presented their detailed 3D-US evaluation. The surface area of vermis (SAV), brainstem-vermis, and brainstem-tentorium angles were measured by 3D-US. The good prognosis was defined as normal neurodevelopmental outcome. MRI and autopsy were the diagnostic reference standard. RESULTS: There was a significant difference between 2D-US (60.0%, 36/60) and 3D-US (94.8%, 55/58) for the diagnostic accuracy (P < .01). Prenatal 3D-US prediction model was established with observed/expected SAV as the main predictor (area under the curve [AUC]: 0.901; 95% CI, 0.810-0.992, P < .001). When it was more than 107.5%, the prognosis seemed to be good (sensitivity: 96.4%, specificity: 26.7%), which led to consideration of mega cisterna magna, Blake pouch cyst, or small arachnoid cyst. The prognosis appeared to be poor when it was less than 73% (sensitivity: 71.4%, specificity: 100%), and the diagnosis tended to be a Dandy-Walker malformation, vermian hypoplasia, and cerebellar hypoplasia. Brainstem-vermis and brainstem-tentorium angles were the secondary indicators (AUC: 0.689 vs 0.761; 95% CI, 0.541-0.836 vs 0.624-0.897, P = .014 vs.001). CONCLUSIONS: It seems that the exact types of PFA can be effectively diagnosed by quantitative indicators of 3D-US.

Comparison of efficacy and safety of two fixed-dose combination regimens for tuberculosis in the Chinese population.

To date, there have been few studies on the dosage of fixed-dose combination (FDC) for the treatment of tuberculosis (TB) in the Chinese population. The aim of this study was to evaluate the efficacy and safety of two FDC regimens in two provinces with a high tuberculosis burden. A total of 2,353 newly diagnosed active pulmonary TB patients were recruited from Shandong Province (n=1,223) and Jilin Province (n=1,130). Participants received FDC treatment for six months (intensive phase and continuation phase). The difference in the two regimens was the dosage of FDC in the continuation phase. For Shandong Province, the cure rate was 96.4% (370/384). In all, 1,172 patients successfully completed the treatment, the success rate being 95.8% (1,172/1,223). For Jilin Province, the cure rate was 92.5% (345/373): 1,109 patients successfully completed the treatment and the treatment success rate was 98.1% (1,109/1,130). Significant differences were observed in the cure rate (X2=5.382, p=0.020) and the treatment success rate (X2=10.581, p=0.001) between the two provinces. The integral analysis showed that both regimens had similar efficacy, but the regimen of Jilin Province was inferior to that of Shandong Province in terms of safety.

Prenatal diagnosis of fetal skeletal dysplasia using targeted next-generation sequencing: an analysis of 30 cases.

BACKGROUND: This study aims to provide genetic diagnoses for 30 cases of fetal skeletal dysplasia, and a molecular basis for the future prenatal diagnosis of fetal skeletal dysplasia. METHODS: A total of 30 cases of fetal skeletal dysplasia detected with ultrasound between January 2014 and June 2017 were analyzed. Among these fetuses, 15 fetuses had local skeletal malformations, while 15 fetuses had short limb malformations. Samples of fetal umbilical cord blood, amniotic fluid, and/or aborted tissue were collected from all cases. Karyotyping, whole genome sequencing, and targeted next-generation sequencing of skeletal disease-related pathogenic genes were performed, as needed. Blood samples were taken from the parents for verification using Sanger sequencing. RESULTS: Among the 30 cases of fetal skeletal dysplasia, two cases were diagnosed with trisomy 18. However, none of these cases were identified with any microdeletions or microreplications associated with skeletal dysplasia. Among the 28 chromosomally normal cases with fetal skeletal dysplasia, 21 cases were detected with mutations in genes related to skeletal diseases. Furthermore, collagen gene mutations were detected in six fetuses with short limb malformations, while heterozygous disease-causing mutations in the fibroblast growth factor receptor 3 (FGFR3) gene were detected in seven fetuses. The remaining fetuses carried mutations in other various genes, including tumor protein p63 (TP63), cholestenol delta-isomerase (EBP), cholinergic receptor nicotinic gamma subunit (CHRNG), filamin B (FLNB), and SRY-box 9 (SOX9). Three compound heterozygous mutations in CHRNG, COL11A2 and SOX9 were carried by phenotypically healthy parents. CONCLUSION: Targeted next-generation sequencing can significantly improve the prenatal diagnoses of fetal skeletal dysplasia, providing parents with more precision medicine, and improved genetic counseling.

Multicenter evaluation of membrane-based smear microscopy for detecting acid-fast bacilli in China.

OBJECTIVE: To assess the feasibility and reliability of using membrane-based smear microscopy at peripheral laboratories in China. METHODS: The clinical case control study was conducted in five tuberculosis (TB) dispensaries from September 2014 to May 2016. The membrane-based microscopy and direct smear microscopy were performed to compare the sensitivity, specificity, and the examination time for both methods was also analyzed. RESULTS: A total of 5359 TB suspects were consecutively enrolled from 5 TB dispensaries, and 9915 specimens were finally analyzed. The sensitivity for membrane-based microscopy and direct smear microscopy was 76.9% (95% CI, 75.4-78.4) and 53.8% (95% CI, 52.1-55.6) respectively, and the specificity was 96.8% (95% CI, 96.4-97.2) and 99.2% (95% CI, 99.0-99.4) respectively. The sensitivity and specificity were both significantly different (P<0.001) between the two methods. The examination time for membrane-based smear microscopy (209.1±112.0 seconds) was significantly shorter than that for direct smear microscopy (253.1±79.4 seconds) (P<0.05). CONCLUSIONS: Membrane-based smear microscopy showed higher sensitivity and a shorter examination time in comparison with direct smear microscopy and it could be used at peripheral laboratories in China.

Vitamin D status of tuberculosis patients with diabetes mellitus in different economic areas and associated factors in China.

BACKGROUND: Vitamin D could be a mediator in the association between tuberculosis (TB) and diabetes mellitus (DM). A large scale multi-center study confirmed that TB patients with DM had significantly lower serum vitamin D level compared with those without DM and reported that DM was a strong independent risk factor for vitamin D deficiency. OBJECTIVES: This study was undertaken to determine amongst patients with both TB and DM living in different economically defined areas in China: i) their baseline characteristics, ii) their vitamin D status and iii) whether certain baseline characteristics were associated with vitamin D deficiency. METHODS: In DM-TB patients consecutively attending seven clinics or hospitals, we measured 25 hydroxycholecalciferol at the time of registration using electrochemiluminescence in a COBASE 601 Roche analyser by chemiluminescence immunoassay. Data analysis was performed using chi square test and multivariate logistic regression. RESULTS: There were 178 DM-TB patients that included 50 from economically well-developed areas, 103 from better-off areas and 25 from a poverty area. Median vitamin D levels in well-developed, better-off and poverty areas were 11.5ng/ml, 12.2ng/ml and 11.5ng/ml respectively. Amongst all patients, 149 (84%) had vitamin D deficiency-91 (51%) with vitamin D deficiency (10-19.9 ng/ml) and 58 (33%) with severe deficiency (< 10 ng/ml). There was a significantly higher proportion with vitamin D deficiency in the poverty area. The adjusted odds of vitamin D deficiency (25-(OH)D3 <20 ng/ml) were significantly higher in those with longer history of DM (P = 0.038) and with HbA1c≥10% (P = 0.003). CONCLUSION: Over 80% of TB patients with DM in China were vitamin D deficient, with risk factors being residence in a poverty area, a long duration of DM and uncontrolled DM. TB programme managers and clinicians need to pay more attention to the vitamin D status of their patients.

Vitamin D status in tuberculosis patients with diabetes, prediabetes and normal blood glucose in China: a cross-sectional study.

OBJECTIVE: The association between tuberculosis (TB), diabetes mellitus (DM) and vitamin D status is poorly characterised. We therefore: (1) determined vitamin D status in patients with TB in relation to whether they had normal fasting blood glucose (FBG), pre-DM or DM and (2) assessed whether baseline characteristics in patients with TB, including their DM status, were associated with vitamin D deficiency. METHODS: In patients with TB consecutively attending six clinics or hospitals in China, we measured 25-hydroxycholecalciferol (25-(OH)D3) at the time of registration using electrochemiluminescence in a COBASE 601 Roche analyser by chemiluminescence immunoassay. Data analysis was performed using the χ2 test, ORs and multivariate logistic regression. RESULTS: There were 306 eligible patients with TB, including 96 with smear positive pulmonary TB, 187 with smear negative pulmonary TB and 23 with extrapulmonary TB. Of these, 95 (31%) had normal blood glucose, 83 (27%) had pre-DM and 128 (42%) had DM. Median serum vitamin D levels were 16.1 ng/mL in patients with TB with normal FBG, 12.6 ng/mL in patients with TB with pre-DM and 12.1 ng/mL in patients with TB with DM (p<0.001). The study highlighted certain baseline characteristics associated with vitamin D deficiency (25-(OH)D3<20 ng/mL). After adjusting for confounders, serum vitamin D deficiency was significantly more common in patients being registered in the cold season (November to April) (p=0.006) and in those with DM (p=0.003). CONCLUSION: Vitamin D levels are lower in patients with TB with pre-DM and DM and are also affected by certain baseline characteristics that include being registered in the cold season and having DM. TB programmes need to pay more attention to vitamin D status in their patients, especially if there is coexisting pre-DM or DM.

Uniparental disomy and prenatal phenotype: Two case reports and review.

RATIONALE: Uniparental disomy (UPD) gives a description of the inheritance of both homologues of a chromosome pair from the same parent. The consequences of UPD depend on the specific chromosome/segment involved and its parental origin. PATIENT CONCERNS: We report prenatal phenotypes of 2 rare cases of UPD. DIAGNOSES: The prenatal phenotype of case 1 included sonographic markers such as enlarged nuchal translucency (NT), absent nasal bone, short femur and humerus length, and several structural malformations involving Dandy-Walker malformation and congenital heart defects. The prenatal phenotype of Case 2 are sonographic markers, including enlarged NT, thickened nuchal fold, ascites, and polyhydramnios without apparent structural malformations. INTERVENTIONS: Conventional G-band karyotype appears normal in case 1, while it shows normal chromosomes with a small supernumerary marker chromosome (sSMC) in case 2. Genetic etiology was left unknown until single-nucleotide polymorphism-based array (SNP-array) was performed, and segmental paternal UPD 22 was identified in case 1 and segmental paternal UPD 14 was found in case 2. OUTCOMES: The parents of case 1 chose termination of pregnancy. The neonate of case 2 was born prematurely with a bellshaped small thorax and died within a day. LESSONS: UPD cases are rare and the phenotypes are different, which depend on the origin and affected chromosomal part. If a fetus shows multiple anomalies that cannot be attributed to a common aneuploidy or a genetic syndrome, or manifests some features possibly related to an UPD syndrome, such as detection of sSMC, SNP-array should be considered.

[Genetic polymorphism of glutathione-S-transferase M1 and T1: a systematic review in Chinese population and a pilot study in smear-positive pulmonary tuberculosis cases of Jilin province].

OBJECTIVE: To investigate the distribution of glutathione-S-transferase M1 (GSTM1) and T1 (GSTT1) genes polymorphisms in Chinese population and smear-positive pulmonary tuberculosis cases of Jilin province. METHODS: Articles about GSTM1 and GSTT1 genes polymorphisms published before 2009 in China were searched. The study population was obtained from fourteen counties (or districts) of Jilin province, which included all cases from November, 2007 to May, 2008, totally 1120. The genotypes of GSTM1 and GSTT1 were detected by multiplex PCR technique. RESULTS: The frequencies of GSTM1 and GSTT1 'null' genotypes and combination M1-T1 'null' genotype acquired from systematic review were 54.2%, 46.8% and 26.2%, respectively, in Chinese Hans they were 53.4%, 44.9% and 25.5%, and in our research they are 57.2%, 20.4% and 13.7%, respectively. No significant differences between the frequencies of males and females as well as among that of different age groups were observed (P > 0.05). The frequency of GSTM1 'null' genotype in our research is slightly higher than that in systematic review (P = 0.016) , and the frequencies of GSTT1 'null' genotype and combination M1-T1 'null' genotype and are significantly lower than those in systematic review (both P < 0.001). CONCLUSION: The frequencies of GSTM1 and GSTT1 'null' genotypes were different among ethnic. The statistical difference between systematic review and our research may due to our large sample size and mostly Southern people in previous studies.