Polysomnography outcomes of sleep endoscopy-directed intervention in surgically naïve children at risk for persistent obstructive sleep apnea.

PURPOSE: Drug-induced sleep endoscopy (DISE) is useful in children with obstructive sleep apnea (OSA) that persists after adenotonsillectomy (AT), but its utility in surgically naïve children is unclear. We report polysomnography outcomes of surgically naïve children who underwent DISE-directed intervention because they were considered high risk for persistent OSA after adenotonsillectomy. METHODS: This study is a case series of 62 surgically naïve children with OSA who were considered high risk for persistence after AT and underwent DISE-directed intervention with pre- and postoperative polysomnography between 2012 and 2016. Analysis was performed with the paired t test. RESULTS: Children were on average 5.9 (± 5.5, 0.2-18.6) years old at the time of surgery, 68% male, 18% obese, and 60% white. Thirty-eight percent had a syndromic diagnosis: 19% trisomy 21, 11% hypotonic neuromuscular disorder, and 8% craniofacial condition. The remaining 62% were non-syndromic but underwent DISE because they had at least one risk factor for OSA persistence after AT (age > 7 years, black race, 1+ tonsils, obesity, and/or severe OSA). Forty-two percent underwent AT, while 58% underwent treatment other than AT, including 18% who had multilevel surgery. Children improved significantly in 4 out of 5 polysomnography parameters tested, including obstructive apnea-hypopnea index (oAHI; 22.2 to 7.2, p < 0.01) and oxygen nadir (82 to 87, p < 0.01). Thirty-eight (61%) had a postoperative oAHI < 5; 16 (21%) had a postoperative oAHI < 2. CONCLUSION: DISE resulted in intervention other than AT in 58% of surgically naïve children at high risk for persistent OSA after AT. DISE-directed intervention resulted in significant mean improvement in postoperative OSA.

Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: A multicentre cohort study.

BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. METHODS: A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP). RESULTS: Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001). CONCLUSIONS: HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.

Blunt dopamine transmission due to decreased GDNF in the PFC evokes cognitive impairment in Parkinson's disease.

Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson's disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson's disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson's disease. We then established a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson's disease.

A Mammography-Based Nomogram for Prediction of Malignancy in Breast Suspicious Calcification.

AIM: To establish a predictive nomogram for malignancy risk stratification of micro-calcifications (MCCs) detected on mammography. MATERIALS AND METHODS: Consecutive mammograms from January 2017 to March 2021 were retrospectively reviewed. Traditional clinical features were recorded and mammographic features were estimated according to the 5th BI-RADS. A nomogram was developed to graphically predict the malignancy risk based on multivariate logistic regression analysis. The discrimination and calibration performance of the prediction model was assessed. RESULTS: There were 123 cases of suspicious MCCs with final pathological results identified with a malignancy rate of 55.2%. The malignancy rates of subgroups divided according to the morphology and distribution of MCCs, age, menopausal status and the maximum diameter of MCCs were significantly different. Multivariate logistic analysis showed that a menopause status of postmenopausal, maximum diameters of MCCs ≥2 cm, the morphology of MCCs as fine pleomorphic or fine linear or branching, and the distribution of MCCs as linear or segmental were predictive of a higher probability of malignancy. A prediction nomogram was developed based on four risk factors, including menopausal status as well as the maximum diameters, distribution and morphology of the MCCs. The AUC of that nomogram was 0.839 (95%CI:0.771-0.903). CONCLUSION: In mammography, the morphology, distribution and maximum diameter of MCCs, and the menopausal status are independent predictors of malignant suspicious MCCs and are readily available in the clinical setting. The nomogram developed in this study for individualized malignancy risk stratification of suspicious MCCs shows a reliable discrimination performance.

[A Prognostic Nomogram Based on Response to Bortezomib and BTK Expression for Treatment-Experienced Multiple Myeloma Patients].

OBJECTIVE: To establish a prognostic nomogram based on response to bortezomib and BTK expression for treatment-experienced multiple myeloma patients. METHODS: The Oncomine database was utilized to determine BTK expression, sex, age, albumin, Mayo index, response to bortezomib treatment, follow-up time and survival status in multiple myeloma(MM) patients. Cut-off point for BTK expression was calculated using R software. Univariate and multivariate analyses by Cox proportional hazards regression were then performed. Significant prognostic factors were combined to build a nomogram. The discrimination ability and predictive accuracy of the nomogram were evaluated using the index of concordance (C-index) and calibration curves. RESULTS: Multivariate analysis showed that response to bortezomib, BTK expression and sex were independent risk factors for prognosis. The C-index value of the nomogram made according to the independent risk factors was 0.729 (95%CI, 0.642-0.8164). The calibration curves showed good consistency between predicted and actual survivals for 1-year and 2-year overall survival. CONCLUSION: The proposed nomogram is accurate in predicting the prognosis of patients with MM.

[Clinical Significance of sFLC/MP Level and Light Chain Escape in Patients with Multiple Myeloma Relapse].

OBJECTIVE: To explore the effects of serum free light chain (sFLC) and monoclonal protein (MP) on the efficacy and prognosis of patients with multiple myeloma relapse, and investigate the clinical value of light chain escape (LCE). METHODS: The relationship between sFLC/MP levels and clinical features and outcomes in 71 patients with multiple myeloma after relapse were retrospective analyzed. The patients were divided into MO group, MLC group and LCE group according to different levels of sFLC/MP after relapse. Then the clinical indicators, efficacy, survival after relapse (SAR) and overall survival (OS) of the patients in each group were compared. Meanwhile a paired sample t test was used to analyze the relevant indicators of the patients before and after relapse in LCE group. RESULTS: There were significant differences in ISS stage, the levels of Hb, PLT, ALB, SFLC/MP and the proportion of myeloplasma cells afte relapse (P<0.05). The initial treatment effect of the patients in MO group was better than those in the other groups, and the LCE group was the worst (P<0.05). Comparison of relevant indicators between the patients before and after relapse in LCE group showed that the levels of MP, Hb and PLT decreased significantly, while sFLC, LDH and Cr increased significantly (P<0.05). Multivariate analysis showed that MO was the independent risk factor affecting SAR, while MO and LCE were the independent risk factors affecting OS (P<0.05) of the patients.The average SAR of the patients in MO, MLC and LCE group was 41, 28.6 and 23.5 months (P=0.002), and the average OS was 79.6, 57.9 and 41 months (P<0.001), respectively. The patients in MO group showed longer SAR and OS, while the LCE group was the shortest. CONCLUSION: After relapse, patients only with elevated MP levels have a better curative effect and prognosis, while only with elevated sFLC levels have poor curative effects and prognosis, which suggesting that sFLC/MP levels can be used as a good indicator for predicting the prognosis of multiple myeloma patients.The appearance of LCE indicates disease progression, poor prognosis and early relapse.

Drug-induced sleep endoscopy directed surgery improves polysomnography measures in overweight and obese children with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea affects approximately 1-4% of all children, with increased prevalence amongst overweight and obese children. OBJECTIVE: To assess the effects of drug-induced sleep endoscopy (DISE)-directed surgery on polysomnography parameters in obese and overweight children. MATERIAL/METHODS: A retrospective case-series was performed on obese and overweight pediatric patients who underwent clinically indicated DISE-directed surgery. Forty children met the inclusion criteria, including: body mass index ≥85%, DISE-study, and pre- and post-DISE polysomnography. Patients were divided into surgically naïve (n = 23) and prior adenotonsillectomy (n = 17) groups. Demographic and clinical characteristics were examined with chi-square and Wilcoxon rank-sum test. Polysomnography parameters were compared with Wilcoxon signed rank test. RESULTS: Of 40 children with mean BMI 94% and mean age 8 ± 6 years old, 17 (43%) underwent a previous adenotonsillectomy. Overall, significant improvements were observed in the apnea-hypopnea index (AHI; 25.0 to 9.9 events/hour, p < .01) and oxygen nadir (82.7% to 88.5%, p < .01). A similar pattern was observed among the surgically naïve (AHI: 35.9 to 12.7 events/hour, p = .04; oxygen nadir: 79.7% to 86.4%, p = .2) and post-adenotonsillectomy groups (AHI: 10.4 to 6.2 events/hour, p = .02; oxygen nadir: 86.7% to 91.2%, p < .01). CONCLUSIONS/SIGNIFICANCE: Polysomnography parameters significantly improved following DISE-directed interventions in obese and overweight children with obstructive sleep apnea.

Osteoblastoma of the breast:An uncommon and easily overlooked location.

Osteoblastoma is a rare benign osseous neoplasm that accounts for 1%-3% of all primary bone tumors. Osteoblastomas can involve any part of the skeleton, but mainly occurs in the spine and other long bones, rarely in extra-skeletal areas. Extra-skeletal osteoblastomas arise from tissues outside of the bone, and only a few cases have been reported previously. To our knowledge, only one case of osteoblastoma in the breast has been described in the English literature. Here, we report another case of a breast osteoblastoma in a middle-aged woman, which was initially detected by ultrasound examination and digital mammography, and then was confirmed by histopathology. In this report, the imaging features and differential diagnosis of breast osteoblastoma are discussed.

Possible role of glial cell line-derived neurotrophic factor for predicting cognitive impairment in Parkinson's disease: a case-control study.

Glial cell line-derived neurotrophic factor (GDNF) plays an important role in the protection of dopaminergic neurons, but there are few reports of the relationship between GDNF and its precursors (α-pro-GDNF and ß-pro-GDNF) and cognitive impairment in Parkinson's disease. This study aimed to investigate the relationship between the serum levels of GDNF and its precursors and cognitive impairment in Parkinson's disease, and to assess their potential as a diagnostic marker. Fifty-three primary outpatients and hospitalized patients with Parkinson's disease (23 men and 30 women) with an average age of 66.58 years were enrolled from the Affiliated Hospital of Xuzhou Medical University of China in this case-control study. The patients were divided into the Parkinson's disease with cognitive impairment group (n = 27) and the Parkinson's disease with normal cognitive function group (n = 26) based on their Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating scores. In addition, 26 age- and sex-matched healthy subjects were included as the healthy control group. Results demonstrated that serum GDNF levels were significantly higher in the Parkinson's disease with normal cognitive function group than in the other two groups. There were no significant differences in GDNF precursor levels among the three groups. Correlation analysis revealed that serum GDNF levels, GDNF/α-pro-GDNF ratios, and GDNF/ß-pro-GDNF ratios were moderately or highly correlated with the Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating scores. To explore the risk factors for cognitive impairment in patients with Parkinson's disease, logistic regression analysis and stepwise linear regression analysis were performed. Both GDNF levels and Hoehn-Yahr stage were risk factors for cognitive impairment in Parkinson's disease, and were the common influencing factors for cognitive scale scores. Neither α-pro-GDNF nor ß-pro-GDNF was risk factors for cognitive impairment in Parkinson's disease. A receiver operating characteristic curve of GDNF was generated to predict cognitive function in Parkinson's disease (area under the curve = 0.859). This result indicates that the possibility that serum GDNF can correctly distinguish whether patients with Parkinson's disease have cognitive impairment is 0.859. Together, these results suggest that serum GDNF may be an effective diagnostic marker for cognitive impairment in Parkinson's disease. However, α-pro-GDNF and ß-pro-GDNF are not useful for predicting cognitive impairment in this disease. This study was approved by Ethics Committee of the Affiliated Hospital of Xuzhou Medical University, China (approval No. XYFY2017-KL047-01) on November 30, 2017.

Association of circulating cystatin C levels with type 2 diabetes mellitus: a systematic review and meta-analysis.

INTRODUCTION: This study aimed to systemically summarize the present literature about circulating cystatin C (Cys C) levels in type 2 diabetes mellitus (T2DM) and provide a more precise evaluation of Cys C levels in T2DM. MATERIAL AND METHODS: Relevant studies about Cys C concentrations in T2DM were searched in PubMed, EMBASE and the Cochrane Library database (up to Oct 31 2018). We computed the pooled standard mean difference (SMD) with its 95% confidence interval (CI) of Cys C levels through a random-effect model. The Q test and the I2 statistic were used to assess and quantify between-study heterogeneity; publication bias was evaluated through a funnel plot and Egger's linear regression test. RESULTS: After the literature search and screening process, 14 studies with 723 T2DM patients and 473 healthy controls were finally included in the meta-analysis. The results showed that T2DM patients had significantly higher Cys C levels compared to healthy controls (SMD = 1.39, 95% CI: 0.92-1.86, p < 0.001). Publication bias was not detected based on the symmetrical shape of the funnel plot and the results of Egger's test (p = 0.452). Subgroup analyses suggested that variables of human race, age, gender, study sample size and disease duration have a relationship with Cys C level in T2DM patients. CONCLUSIONS: Overall, our study suggests that patients with T2DM have an elevated circulating Cys C level compared to healthy controls, and it is associated with race, age, gender, study sample size and disease duration. Further investigations are still needed to explore the causal relationship of aberrant Cys C concentrations in T2DM.

Clonal evolution of AML1-ETO coexisting with BCR-ABL and additional chromosome abnormalities in a blastic transformation of chronic myeloid leukemia.

Blast crisis develops in a minority of patients with chronic myeloid leukemia even in the era of tyrosine kinase inhibitor (TKI) therapy. Reports suggest that we know little about the mechanism of BCR-ABL and AML1-ETO co-expression in blast crisis of chronic myeloid leukemia, and that other chromosomal abnormalities also coexist. Here, we document an unusual and interesting case of a 51-year-old female diagnosed in the chronic phase of chronic myeloid leukemia. After undergoing TKI treatment for 3 months, her bone marrow aspirates in the chronic phase had transformed to blast crisis. Molecular genetic testing indicated she was positive for p210 form of BCR-ABL (copy number decreased from 108.91% to 56.96%) and AML1-ETO fusion (copy number, 5.65%) genes and had additional chromosomal abnormalities of t(8; 21)(q22; q22)/t(9; 22)(q34; q11), t(2; 5)(p24; q13) and an additional +8 chromosome.

[Value of Red Blood Cell Distribution Width and Fibrinogen Level for Evaluation of the Therapeutic Efficacy and Prognosis in Patients with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the value of red blood cell distribution width (RDW) and fibrinogen (Fib) level for the evaluation of therapeutic efficacy and prognosis in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The relationship between RDW/Fib at initial diagnosis and efficacy and the clinical outcome was retro-spectively analyzed based on the study of 105 patients with DLBCL. The patients were divided into two groups: low RDW group (≤15%) and high RDW group (>15%), low Fib group (Fib≤4 g/L) and high Fib group (Fib>4 g/L) according to the normal values of RDW and Fib. Therapeutic efficacy, overall survival (OS) time and progression free survival (PFS) time were compared between two groups. The correlation between each factors and efficacy, prognosis was analyzed by univariate and multivariate regression. RESULTS: The therapeutic efficacy (P<0.001), OS time(P=0.004), and PFS time(P=0.007) were poorer in the high RDW group as compared with the low RDW group. The efficacy (P=0.015) and PFS time(P=0.04) were poorer in the high Fib group as compared with the low Fib group. Multivariate analysis showed that high RDW was the independent risk factor for efficacy of DLBCL patients (OR=3.394, 95% CI 1.093-10.539, P=0.035). CONCLUSION: High RDW and high Fib associate with poor efficacy in DLBCL patients.

[Prognostic Value of Immune Status Changes after Chemotherapy in Patients with Newly Diagnosed Multiple Myeloma].

OBJECTIVE: To investigate the prognostic significance of immune changes in patients with newly diagnosed multiple myeloma(MM) after chemothrapy. METHODS: The clinical data of 99 patients with multiple myeloma received treatment in Department of Hematology, Lanzhou University Second Hospital from April 2011 to December 2017 were collected and retrospectively analyzed. The change of immune status was defined by changes of lymphocyte/monocyte ratio(LMR) level. The prognosis value of age, sex, typing, hemoglobin (Hb), ß2-microglobulin (ß2-MG), lactate dehydrogenase (LDH), albumin (albumin, ALB) and LMR changes were investigated in patients with newly diagnosed MM, and the relationship between above inentioned factors and changes of LMR was also explored. Overall survival rate between different subgroups was compared by using Kaplan-Meier curves and detected by Log-rank tests. Univariate and multivariate analysis of prognosis was performed by using the COX proportional hazards regression model. Paired samples Wilcoxon test were used to compare changes in ALC, AMC and LMR before and after chemotherapy, and logistic regression was used to investigate the clinical factors that affect the changes of LMR. RESULTS: The median value of ALC increased from 1.25 (0.84-1.81)×109/L to 1.39 (1.02-1.9)×109/L (P=0.029) after treated for 1 month; the median value of AMC decreased from 0.37 (0.23-0.47) ×109/L to 0.29 (0.2-0.44)×109/L (P=0.026), and the median value of LMR increased from 3.552 (2.405-5.208) to 5.138 (3.22-6.471) (P=0.002). Multivariate survival analysis showed that increasing of LMR (HR 0.459, 95% CI 0.241-0.875, P=0.018) and LDH (HR 2.368, 95% CI 1.123-4.995, P=0.024) were considered to be the independent factors affecting the prognosis of MM patients. CONCLUSION: The increasing of LMR level after treatment indicates a longer survival time of newly prognostic MM patients. Combination with LMR can not only reflect the effect of treatment on the immune status, but also predict the prognosis of MM patients much better.

Polysomnography outcomes in children with small tonsils undergoing drug-induced sleep endoscopy-directed surgery.

OBJECTIVES/HYPOTHESIS: The optimal surgical treatment to improve sleep apnea in children with small tonsils is not known. Drug-induced sleep endoscopy (DISE) may be useful in selecting effective surgical procedures for this patient population. This study compared polysomnography (PSG) measures before and after DISE-directed surgery in children with small tonsils. We hypothesize that DISE-directed surgery improves PSG measures in children with small tonsils. We also aimed to identify the most common surgery performed in this population. STUDY DESIGN: Retrospective chart review. METHODS: A retrospective review was performed of subjects who underwent DISE at a single pediatric tertiary care center over a 6-year period. Inclusion criteria were 1+ tonsils and PSG performed before and after DISE-directed surgery. Exclusion criteria were previous tonsillectomy and tonsils score 2+ or greater. Pre- and postoperative PSG parameters were compared using paired t tests. RESULTS: Average age was 7 ± 4 years old at the time of surgery. The most common DISE-directed intervention was supraglottoplasty (n = 23). DISE-directed surgery significantly improved mean apnea-hypopnea index (AHI) from 14.4 to 8.0 (P = .02). Although improvements were seen in mean obstructive AHI (12.5 to 5.5), O2 nadir (87.0 to 88.3), and ODI (10.6 to 5.8), these measures did not reach statistical significance. CONCLUSIONS: DISE-directed surgery significantly improves AHI in children with small tonsils. The most common intervention performed on these children was supraglottoplasty. Interestingly, adenotonsillectomy was rarely performed in this cohort. Additionally, supraglottic collapse, prompting supraglottoplasty, is difficult to accurately assess in an awake child, supporting use of a DISE-directed approach in this patient population. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:2771-2774, 2019.

[Clinical study on acupuncture combined with rehabilitation therapy for treatment of poststroke shoulder-hand syndrome].

OBJECTIVE: To observe therapeutic effect of acupuncture combined with rehabilitation therapy on poststroke shoulder-hand syndrome. METHODS: One hundred and twenty cases of poststroke shoulder-hand syndrome were randomly divided into an acupuncture-rehabilitation group, an acupuncture group and a rehabilitation group, 40 cases in each group. The acupuncture-rehabilitation group were treated with acupuncture at Jianyu (LI 15), Jianqian, Jianliao (TE 14), etc. in combination with motor therapy (rehabilitation training), the acupuncture group with simple acupuncture therapy, and the rehabilitation group with simple motor therapy. Upper extremity motor function, pain, joint activity were used for assessment of therapeutic effects. RESULTS: The total effective rate of 87.5% in the acupuncture-rehabilitation group was significantly better than 67.5% in the acupuncture group and 65.0% in the rehabilitation group (P<0.01); acupuncture combined with rehabilitation therapy could significantly improve upper limb motor function, pain and joint activity with very significant differences as compared with the acupuncture group and the rehabilitation group (P<0.01). CONCLUSION: Acupuncture combined with rehabilitation therapy has a high cured rate and an obvious therapeutic effect on poststroke shoulder-hand syndrome.