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1.
BMC Med Imaging ; 20(1): 50, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32408867

RESUMO

BACKGROUND: To investigate the ability of amide proton transfer (APT) weighted magnetic resonance imaging (MRI), arterial spin labeling (ASL), diffusion weighted imaging (DWI) and the combination for differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs). METHODS: Twenty-seven patients including nine LGGs and eighteen HGGs underwent conventional, APT, ASL and DWI MRI with a 3.0-T MR scanner. Histogram analyses was performed and quantitative parameters including mean apparent diffusion coefficient (ADC mean), 20th-percentile ADC (ADC 20th), mean APT (APT mean), 90th-percentile APT (APT 90th), relative mean cerebral blood flow (rCBF mean) and relative 90th-percentile CBF (rCBF 90th) were compared between HGGs and LGGs. The diagnostic performance was evaluated with receiver operating characteristic (ROC) analysis of each parameter and their combination. Correlations were analyzed among the MRI parameters and Ki-67. RESULTS: The APT values were significantly higher in the HGGs compared to the LGGs (p <  0.005), whereas ADC values were significantly lower in HGGs than LGGs (P <  0.0001). The ADC 20th and APT mean had higher discrimination abilities compared with other single parameters, with the area under the ROC curve (AUC) of 0.877 and 0.840. Adding ADC parameter, the discrimination ability of APT and rCBF significantly improved. The ADC was negatively correlated with the APT and rCBF value, respectively, while APT value was positively correlated with rCBF value. Significant correlations between ADC values and Ki-67 were also observed. CONCLUSIONS: APT and DWI are valuable in differentiating HGGs from LGGs. The combination of APT, DWI and ASL imaging could improve the ability for discriminating HGGs from LGGs.

2.
Med Ultrason ; 22(2): 183-188, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32399526

RESUMO

AIM: To test the ability of carotid stiffness evaluated by using ultrafast ultrasound imaging to indicate coronary atherosclerosis and its association with the severity of coronary artery disease (CAD). MATERIAL AND METHODS: This cross-sectional study included 131 patients with CAD and 60 normal controls. Carotid intima-media thickness (cIMT) was measured by two-dimensional ultrasound. Carotid stiffness was determined by ultrafast ultrasound imaging, with which the carotid pulse wave velocity at the beginning (PWVBS) and end (PWVES) of systole were calculated. Gensini scores based on coronary angiography were used to estimate the severity of CAD. RESULTS: Compared with normal controls, the CAD patients had higher carotid diameters, cIMT, PWVBS and PWVES (p < 0.05). In the CAD group, Gensini scores correlated significantly with cIMT, PWVBS and PWVES (r = 0.279, p = 0.001; r = 0.661, p < 0.001; r = 0.620, p < 0.001; respectively). The multivariate analysis further indicated that PWVBS, PWVES and body mass index were independently associated with the Gensini score (ß = 0.466, p < 0.001; ß = 0.308, p < 0.001; and ß = 0.209, p = 0.001; respectively). In addition, the sensitivity and specificity were 54% and 83%, respectively, for PWVBS (cutoff value, 6.9 m/s; area under the receiver operating characteristic curve, 0.70) and 64% and 83%, respectively, for PWVES (cutoff value, 8.0 m/s; area under the curve, 0.73). CONCLUSIONS: Increased carotid PWVBS and PWVES detected by ultrafast ultrasound imaging as indices of carotid stiffness might serve as promising indicators for CAD and its severity.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32417490

RESUMO

Delayed reconstitution of the immune system is a long-recognized complication after allogeneic hematopoietic cell transplantation (HCT). Specifically, loss of T-cell diversity has been thought to contribute to infectious complications, graft versus host disease (GVHD) and disease relapse. We performed serial high-resolution next generation sequencing of TCR-ß in 99 related or unrelated donor (51 unrelated, 39 related) HCT (55 reduced intensity conditioning, 44 myeloablative conditioning) recipients during the first 3 months after HCT using the immunoSEQ ® Assay. We measured T-cell fraction, clonality (1- Peilou's eveness) and Daley-Smith richness from recipient samples at multiple time points. In agreement with prior studies, we found that although absolute T-cell numbers recover relatively quickly after transplant, T-cell repertoire diversity remains diminished. Restricted diversity was associated with conditioning intensity, use of ATG, and donor type. Increased number of expanded clones compared to donor T-cell clones at Day +30 was associated with the incidence of acute GVHD (HR=1.11, p=5 × 10-5). Even after exclusion of the twelve patients who developed acute GVHD before Day +30, the association between acute GVHD and an increased clonal expansion at Day +30 remained (HR=1.098, p=0.041), indicating that increased clonal T-cell expansion preceded the development of acute GVHD. Our results highlight T-cell clonal expansion as a potential novel biomarker for acute GVHD that warrants further study.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32329689

RESUMO

BACKGROUND: Increasing evidence has shown that p62 plays an important role in tumorigenesis. However, relatively little is known about the association between p62 and tumor invasion and metastasis; in addition, its role in NPC (nasopharyngeal carcinoma, NPC) has been rarely investigated. OBJECTIVE: To investigate the effect of p62 on tumorigenesis and metastasis in nasopharyngeal carcinoma. METHODS: Western blotting, immunofluorescent staining and immunohistochemistry were used to evaluate p62 protein expression. Subsequently, cell viability, colony formation, migration, invasion and autophagy assays were performed. anti-p62 autoantibodies in sera were detected by ELISA. These data were correlated with clinicopathological parameters. RESULTS: We confirmed that p62 was significantly up-regulated in NPC tissues. Furthermore, high expression of p62 was observed in NPC cell lines, and especially in the highly metastatic 5-8F cells. In vitro, down-regulation of p62 inhibited proliferation, clone forming ability, autophagy, migration, and invasion in 5-8F cells, whereas p62 overexpression resulted in the opposite effects in 6-10B cells. Moreover, we confirmed that p62 promotes NPC cell proliferation, migration, and invasion by activating ERK (extracellular signal­regulated kinase, ERK). Clinical analysis indicated that high p62 expression correlates with lymph node and distant metastasis (P<0.05). Serum anti-p62 autoantibodies were increased in NPC patients and levels were associated with metastasis. CONCLUSION: Our data establish p62 targeting ERK as potential determinant in the NPC, which supplies a new pathway to treat NPC. Furthermore, p62 is a potential biomarker which might be closely related to the tumorigenesis and metastasis in NPC.

5.
Mol Genet Genomics ; 2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32306107

RESUMO

Leaf color is an important characteristic of normal chloroplast development. Variegated plants have green- and white-sectored leaves, which can be used to identify important pathways and molecular mechanisms of chloroplast development. We studied two Brassica napus variegation mutants from same one variegated ancestor, designated ZY-4 and ZY-8, which have different degrees of variegation. When grown in identical conditions, the ratio of white sectors in ZY-4 leaves is higher than in ZY-8. In both mutants, the cells in green sectors contain normal chloroplasts; while, the cells in white sectors contain abnormal plastids. Seedling chloroplasts ultrastructure of both mutants showed that the biogenesis of chloroplasts was blocked in early stages; delayed development and structual damage in ZY-4 were more serious than in ZY-8. Employing bulked segregant analysis(BSA), two bulks (BY142 and BY137) from BC2F1 lines derived from ZY-4 and ZS11, and one bulk (BY56) from BC2F1 lines derived from ZY-8 and ZS11, and screening by Brassica 60K SNP BeadChip Array, showed the candidate regions localized in chromosome A08 (BY142), C04 (BY137), and A08 (BY56), respectively. Transcriptome analysis of five seedling development stages of ZY-4, ZY-8, and ZS11 showed that photosynthesis, energy metabolism-related pathways and translation-related pathways were important for chloroplast biogenesis. The number of down- or up-regulated genes related to immune system process in ZY-4 was more than in ZY-8. The retrograde signaling pathway was mis-regulated in both mutants. DEG analysis indicated that both mutants showed photooxidative damages. By coupling transcriptome and BSA CHIP analyses, some candidate genes were identified. The gene expression pattern of carotene biosynthesis pathway was disrupted in both mutants. However, histochemical analysis of ROS revealed that there was no excessive accumulation of ROS in ZY-4 and ZY-8. Taken together, our data indicate that the disruption of carotene biosynthetic pathways leads to the variegation phenotypes of ZY-4 and ZY-8 and there are some functions that can compensate for the disruption of carotene biosynthesis in ZY-4 and ZY-8 to reduce ROS and prevent seedling mortality.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32306192

RESUMO

PURPOSE: To evaluate the diagnostic value of shear wave elastography (SWE) combined with contrast-enhanced ultrasonography (CEUS) in diagnosing thyroid imaging reporting and data system (TI-RADS) category 4a and 4b nodules. METHODS: TI-RADS, SWE, and CEUS features of 71 thyroid nodules (23 benign, 48 malignant) confirmed by postoperative pathological results were retrospectively analyzed. The diagnostic efficiency of each single method and that of a combination of three methods were compared. RESULTS: The sensitivity and specificity in diagnosing thyroid nodules were 70.83% and 65.22% for TI-RADS, 68.75% and 91.30% for SWE, 77.08% and 78.26% for CEUS, and 91.67% and 95.65% for TI-RADS + SWE + CEUS, respectively. The area under the curve for TI-RADS, SWE, CEUS, and TI-RADS + SWE + CEUS in diagnosing thyroid nodules were 0.680, 0.839, 0.799, and 0.937, respectively. A significant difference was observed between a combination of the three methods and any of them alone (p < 0.05). CONCLUSION: Combining SWE and CEUS improves the differential diagnosis of TI-RADS category 4a and 4b nodules.

7.
Blood Adv ; 4(8): 1656-1669, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32324888

RESUMO

Acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic cell transplantation (HCT) is a primary cause of nonrelapse mortality and a major barrier to successful transplant outcomes. Itacitinib is a Janus kinase (JAK)1-selective inhibitor that has demonstrated efficacy in preclinical models of aGVHD. We report results from the first registered study of a JAK inhibitor in patients with aGVHD. This was an open-label phase 1 study enrolling patients aged ≥18 years with first HCT from any source who developed grade IIB to IVD aGVHD. Patients with steroid-naive or steroid-refractory aGVHD were randomized 1:1 to itacitinib 200 mg or 300 mg once daily plus corticosteroids. The primary endpoint was safety and tolerability; day 28 overall response rate (ORR) was the main secondary endpoint. Twenty-nine patients (200 mg, n = 14; 300 mg, n = 15) received ≥1 dose of itacitinib and were included in safety and efficacy assessments. One dose-limiting toxicity was reported (grade 3 thrombocytopenia attributed to GVHD progression in a patient receiving 300 mg itacitinib with preexisting thrombocytopenia). The most common nonhematologic treatment-emergent adverse event was diarrhea (48.3%, n = 14); anemia occurred in 11 patients (38%). ORR on day 28 for all patients in the 200-mg and 300-mg groups was 78.6% and 66.7%, respectively. Day 28 ORR was 75.0% for patients with treatment-naive aGVHD and 70.6% in those with steroid-refractory aGVHD. All patients receiving itacitinib decreased corticosteroid use over time. In summary, itacitinib was well tolerated and demonstrated encouraging efficacy in patients with steroid-naive or steroid-refractory aGVHD, warranting continued clinical investigations. This trial was registered at www.clinicaltrials.gov as #NCT02614612.

8.
Acta Biochim Biophys Sin (Shanghai) ; 52(4): 446-456, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32268372

RESUMO

Self-incompatibility (SI) promotes outbreeding and prevents self-fertilization to promote genetic diversity in angiosperms. Several studies have been carried to investigate SI signaling in plants; however, protein phosphorylation and dephosphorylation in the fine-tuning of the SI response remain insufficiently understood. Here, we performed a phosphoproteomic analysis to identify the phosphoproteins in the stigma of self-compatible 'Westar' and self-incompatible 'W-3' Brassica napus lines. A total of 4109 phosphopeptides representing 1978 unique protein groups were identified. Moreover, 405 and 248 phosphoproteins were significantly changed in response to SI and self-compatibility, respectively. Casein kinase II (CK II) phosphorylation motifs were enriched in self-incompatible response and identified 127 times in 827 dominant SI phosphorylation residues. Functional annotation of the identified phosphoproteins revealed the major roles of these phosphoproteins in plant-pathogen interactions, cell wall modification, mRNA surveillance, RNA degradation, and plant hormone signal transduction. In particular, levels of homolog proteins ABF3, BKI1, BZR2/BSE1, and EIN2 were significantly increased in pistils pollinated with incompatible pollens. Abscisic acid and ethephon treatment partially inhibited seed set, while brassinolide promoted pollen germination and tube growth in SI response. Collectively, our results provided an overview of protein phosphorylation during compatible/incompatible pollination, which may be a potential component of B. napus SI responses.

9.
Biochem Biophys Res Commun ; 526(4): 857-864, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32278547

RESUMO

Ovarian cancer is diagnosed as the most deadly gynecological tumor. Ovarian cancer metastasis affects chemoresistance and confers poor patient prognosis. In present work, we intended to elucidate whether long non-coding RNAs (lncRNAs) TLR8-AS1 regulated cell metastasis and chemoresistance of ovarian cancer, and uncover the molecular mechanism of TLR8-AS1 in the modulation of ovarian cancer progression. Firstly, bioinformatics analyses identified TLR8-AS1 as a cancer-associated fibroblasts regulated lncRNA in ovarian cancer. Further experiments revealed that TLR8-AS1 augmented cell metastasis and chemoresistance of ovarian cancer in vitro and in vivo. Moreover, TLR8-AS1 upregulates TLR8 by stabilizing TLR8 mRNA, thus activating NF-κB signaling and promoting ovarian cancer metastasis and chemoresistance. Besides, TCGA data analysis suggested that TLR8-AS1 is elevated in ovarian cancer in comparison to adjacent non-cancerous tissues. High TLR8-AS1 expression levels were measured in metastatic ovarian cancer and correlated with poor patient prognosis. The clinical data supported the mechanism and biological significance of TLR8-AS1 dysregulation in ovarian cancer development. Our work demonstrates that TLR8-AS1 can be applied as a diagnostic and prognostic indicator for ovarian cancer, and maybe an alternative target for the treatment of ovarian cancer.

10.
BMC Public Health ; 20(1): 435, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245435

RESUMO

BACKGROUND: We examined the physiological, household, and spatial agglomeration characteristics of the health poverty population in China. We identified weak links that affect the implementation of the medical insurance and further improve its effectiveness for health poverty alleviation. METHODS: A national representative sample from the China Health and Retirement Longitudinal Study (CHARLS) was analyzed. The WHO recommended method was adopted to calculate catastrophic health expenditure (CHE) and impoverishment by medical expenses (IME). We created a binary indicator for IME as the outcome variable and applied the treatment-effect model to analyze the determinants of IME. RESULTS: The incidence of IME was 7.2% of the overall population, compared to 20.3% of the sample households trapped in CHE. The incidence of IME enrolled in insurance schemes was 7.4% higher than that of uninsured families (4.8%). Economic level, living area, family size, age of household head, having hospitalized members, and participating in insurance were statistically significant for the occurrence of IME. CONCLUSIONS: The original poverty-promoting policies has not reached the maximum point of convergence with China's current demand for health. The overlapped health vulnerabilities exacerbated the risk of poverty among the elderly and households with high health needs and utilization. In addition, the medical insurance schemes have proven to be insufficient for protection against economic burden of poor households. So, special health needs, age, and household capacity to pay should be comprehensively considered while strengthening the connection between the disease insurance scheme with supplementary insurance.

11.
Angiology ; : 3319720919327, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295385

RESUMO

The clinical outcomes of nicorandil in percutaneous coronary intervention (PCI) are conflicting. We sought to evaluate the effects of nicorandil on periprocedural myocardial injury (PMI) in elective PCI. Eligible studies that reported the effect of nicorandil on PMI in elective PCI were obtained from PubMed, Web of Science, and Cochrane Library (up to October 28, 2019). The outcomes were PMI and major adverse cardiovascular and cerebrovascular events (MACCEs). Ten randomized controlled trials with 1304 patients undergoing elective PCI were evaluated. Nicorandil significantly reduced the incidence of PMI (odds ratio [OR] = 0.48; P = .0003); however, there was no significant difference in MACCEs (OR = 0.80; P = .45) between the 2 groups. Subgroup analyses showed that nicorandil significantly lowered the PMI risk when only patients with stable coronary artery disease (OR = 0.41; P = .0008) were considered and when nicorandil was administered intravenously (OR = 0.41; P = .0007) or orally (OR = 0.33; P = .0001). This meta-analysis suggests that nicorandil could reduce the incidence of PMI without increasing the occurrence of MACCEs in elective PCI. The effect of nicorandil in lowering the PMI risk is associated with the diagnosis of the patients and the route of nicorandil administration.

12.
Neuroradiology ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32242265

RESUMO

PURPOSE: Data on posterior circulation tandem occlusions in acute ischemic stroke are scarce: recognition may be challenging and little is known about optimal treatment strategy. We report our endovascular treatment strategy for posterior circulation tandem occlusion. METHODS: Consecutive patients with posterior circulation tandem occlusions in our centre were enrolled retrospectively. The preferred strategy was "distal-to-proximal" strategy, which means opening the distal occlusion first followed by treatment of the proximal pathology. The imaging characteristics, treatment strategy, clinical outcomes, and complications of patients with posterior circulation tandem occlusions were analyzed. RESULTS: In total, 21 patients with posterior circulation tandem occlusions were enrolled in the study, which accounted for 23.6% of patients with posterior circulation stroke in our centre. The mean age was 60 years (range 32 to 80), and median pre-procedure NIHSS score was 28 (interquartile range: 13-31). Eighteen patients (85.7%) had vertebrobasilar artery tandem occlusions and 3 (14.3%) had basilar artery to basilar artery tandem occlusions. All distal occlusions were successfully recanalized (modified TICI 2b/3). Two (9.5%) of the proximal lesions were not treated. A total of 57.1% of the patients had stents implanted on the proximal occlusions. The rate of mRS 0-3 at 3 months was 57.1% and the mortality rate was 19.0%. CONCLUSION: In patients with acute ischaemic stroke caused by posterior circulation tandem occlusions, we favor "distal-to-proximal" strategy based on the positive results in this small series. Nevertheless, a more extensive study is required to explore the optimal treatment strategy further.

13.
Oncol Rep ; 43(4): 1089-1102, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32323774

RESUMO

Targeted therapy based on specific genetic alterations has been proven to be an effective treatment for various types of cancer. In the present study, we aimed to explore the efficacy of personalized targeted therapy guided by targeted deep sequencing for patients with advanced biliary tract cancer (BTC) after non­radical resection. Targeted deep sequencing was performed on 49 patients with BTC, to whom biologic agents were recommended. Among 32 patients with stage IV and R2 resection (a non­radical resection), 21 patients underwent conventional chemotherapy (mGEMOX), while the remaining 11 patients received a personalized targeted agent. The genomic landscape of the 49 patients with BTC was determined and the results showed that genetic alterations were enriched in the ERBB family and cell cycle pathway. After a median follow­up of 12 months, the 11 BTC patients with personalized targeted therapy showed a median progression­free survival (PFS) of 4.5 months (2.5­20.5 months), a median overall survival (OS) of 12.9 months (4.7­24.8 months) and a disease control rate (DCR) of 63.6%. In the other 21 BTC patients, who were undergoing conventional chemotherapy, the BTC patients had a median PFS of 1.5 months (0.5­11.6 months), a median OS of 4.1 months (1.3­18.4 months), and a DCR of 33.3%. In addition, 36.4% of the patients in the personalized targeted therapy group experienced grade >2 treatment­related toxicity vs. 19.0% of patients in the conventional chemotherapy group. This real­world study suggests that targeted deep sequencing contributes to the guidance of personalized targeted therapy based on individual actionable mutations, which may benefit advanced BTC patients undergoing non­radical resection.

14.
Hepatobiliary Pancreat Dis Int ; 19(2): 138-146, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32139295

RESUMO

BACKGROUND: Transarterial chemoembolization (TACE) and percutaneous microwave coagulation therapy (PMCT) are commonly used to treat intrahepatic recurrent liver cancers. However, there is no information regarding their effectiveness in patients with recurrent intrahepatic cholangiocarcinoma (ICC) after resection. METHODS: A total of 275 patients with localized recurrent ICC who received either TACE (n = 183) or PMCT (n = 92) were studied. A propensity score matching analysis was performed to compare prognostic impact of TACE and PMCT. Prognostic factors for TACE and PMCT were identified respectively. Predictive nomograms for each TACE and PMCT were developed using the Cox independent prognostic factors and were validated in independent patient groups by receiver operating characteristic curves and area under curve values. RESULTS: Both TACE and PMCT provided curativeness in partial patients (5-year overall survival: 21.4% and 6.1%, respectively), but TACE provided better survival benefit in both overall patients (hazard ratio [HR] = 0.71; 95% confidence interval [CI]: 0.50-0.97; P = 0.034) and propensity score matching analysis (HR = 0.69; 95% CI: 0.47-0.98; P = 0.041). Independent prognostic factors for TACE were tumor size >5 cm, poor differentiation, and major resection, whereas poor differentiation, hepatitis B virus infection, cholelithiasis, and lymph node metastasis were identified for PMCT. Both predictive nomograms for TACE and PMCT were validated to be effective with area under curve values of 0.77 and 0.70, respectively. CONCLUSIONS: TACE provided better survival benefits compared to PMCT. However, there was a disparity in prognostic factors, suggesting evaluation of the two nomograms may be supportive in modality selection. Further prospective validation studies are required for the results to be applied in clinical medicine.

15.
J Dig Dis ; 21(4): 237-245, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32166900

RESUMO

OBJECTIVE: To explore the prevalence of and risk factors for gallstone disease in Shanghai, China. METHODS: A population-based cross-sectional study was conducted in Shanghai between 2016 and 2017. Using a three-stage stratified sampling strategy, 4009 participants (1753 men and 2256 women) from 10 districts were enrolled. RESULTS: The overall prevalence of gallstones was 6.83% (6.22% for men vs 7.31% for women, P = 0.173). According to the multivariate analysis, individuals aged ≥40 years (odds ratio [OR] 3.058, 95% confidence interval [CI] 2.110-4.433, P < 0.001), hypertension (OR 1.479, 95% CI 1.076-2.034, P = 0.016), thyroid disease (OR 1.409, 95% CI 1.029-1.928, P = 0.032), a family history of gallstones (OR 2.234, 95% CI 1.362-3.662, P = 0.001) and a waist-to-height ratio ≥0.5 (OR 1.656, 95% CI 1.197-2.292, P = 0.002) had an increased risk of developing gallstones. The risk of gallstone disease was 2.232 (95% CI 1.167-4.268, P = 0.015) times higher in individuals with elevated C4 levels than in those with normal C4 levels. Diabetes (OR 4.144, 95% CI 1.171-14.671, P = 0.028) was a risk factor for the formation of gallstones with diameters ≥1 cm, and men were more susceptible to develop multiple stones (OR 2.356, 95% CI 1.321-4.200, P = 0.004). CONCLUSION: Individuals aged ≥40 years, with a history of hypertension and familial gallstones, a high waist-to-height ratio, thyroid disease and high C4 levels were related to an increased risk of gallstone disease.

16.
Pancreatology ; 20(3): 462-469, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32113937

RESUMO

BACKGROUND: The global burden of pancreatic cancer (PCa) continues to grow. Detailed data on PCa epidemiology are essential for policy-making and appropriate healthcare resource allocation. METHODS: Estimates of incidence, death and disability-adjusted life years (DALYs) of PCa from 1990 to 2017 were collected from the Global Burden of Disease Study 2017. Decomposition analysis was conducted to detect the contributing factors related to PCa incidence variation. The estimated annual percentage change (EAPC) was calculated to quantify the PCa epidemiology trends over a specified interval. RESULTS: Globally, the incidence of PCa cases increased by 129.1% to 447 664 664 (95% uncertainty interval (UI) 438 597-456 295), death increased by 125.2% to 441 082 082 (95% UI 448 960-432 833), and DALYs increased by 107.3% to 9 080 004 (95% UI 8 894 128-9 256 346) between 1990 and 2017. Relatively higher sociodemographic index (SDI) regions were observed with greater incidences, more deaths and a greater number of DALYs of PCa, but relatively lower SDI regions experienced a sharply increasing trend in these measures. Decomposition analysis indicated that the global increase in PCa incidence was driven by the aging population from 2007 to 2017, especially in higher SDI regions. In addition, a significant negative correlation was found between EAPC and ASIR (in 1990) (r = -0.56, P < 0.001). CONCLUSIONS: PCa remains a major public health burden globally. The unfavorable trend in PCa suggesting that further study for prevention should be conducted to forestall the increase in pancreatic cancer.

17.
Blood ; 135(20): 1739-1749, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32160294

RESUMO

Patients who develop steroid-refractory acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation have poor prognosis, highlighting an unmet therapeutic need. In this open-label phase 2 study (ClinicalTrials.gov identifier: NCT02953678), patients aged at least 12 years with grades II to IV steroid-refractory aGVHD were eligible to receive ruxolitinib orally, starting at 5 mg twice daily plus corticosteroids, until treatment failure, unacceptable toxicity, or death. The primary end point was overall response rate (ORR) at day 28; the key secondary end point was duration of response (DOR) at 6 months. As of 2 July 2018, 71 patients received at least 1 dose of ruxolitinib. Forty-eight of those patients (67.6%) had grade III/IV aGVHD at enrollment. At day 28, 39 patients (54.9%; 95% confidence interval, 42.7%-66.8%) had an overall response, including 19 (26.8%) with complete responses. Best ORR at any time was 73.2% (complete response, 56.3%). Responses were observed across skin (61.1%), upper (45.5%) and lower (46.0%) gastrointestinal tract, and liver (26.7%). Median DOR was 345 days. Overall survival estimate at 6 months was 51.0%. At day 28, 24 (55.8%) of 43 patients receiving ruxolitinib and corticosteroids had a 50% or greater corticosteroid dose reduction from baseline. The most common treatment-emergent adverse events were anemia (64.8%), thrombocytopenia (62.0%), hypokalemia (49.3%), neutropenia (47.9%), and peripheral edema (45.1%). Ruxolitinib produced durable responses and encouraging survival compared with historical data in patients with steroid-refractory aGVHD who otherwise have dismal outcomes. The safety profile was consistent with expectations for ruxolitinib and this patient population.

18.
World Neurosurg ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32112936

RESUMO

OBJECTIVE: The relationship between neutrophil-lymphocyte ratio (NLR) and the occurrence of rebleeding in aneurysmal subarachnoid hemorrhage (aSAH) is poorly understood. Our study aimed to investigate the association between NLR on admission and rebleeding following aSAH. METHODS: Clinical and laboratorial data from patients with aSAH were retrospectively collected, including leukocyte, neutrophil, lymphocyte, and NLR. Univariate and multivariate analyses were performed to assess for the association of NLR with rebleeding. We performed propensity-score matching analyses to correct imbalances in patient characteristics between the rebleeding group and nonrebleeding group. RESULTS: Rebleeding occurred in 30 of 716 (4.19%) patients with aSAH in this cohort. Patients with rebleeding had significantly higher NLR comparing with patients without rebleeding (11.27 vs. 5.5; P < 0.05) in the univariate analysis. In the multivariate analysis, NLR was considered as a risk factor of rebleeding (odds ratio, 0.283; 95% confidence interval, 0.130-0.620; P = 0.002), as well as Fisher grade (odds ratio, 0.353, 95% confidence interval, 0.151-0.824; P = 0.016). The area under the curve of the NLR and combined NLR-Fisher grade model was 0.702 and 0.744 (sensitivity was 39.94%, and specificity was 100%) for predicting rebleeding, respectively. After propensity-score matching, the optimal cutoff value for NLR as a predictor for rebleeding following aSAH was determined as 5.4 (sensitivity was 83.33%, and the specificity was 63.33%). CONCLUSIONS: Higher NLR predicts the occurrence of rebleeding and poor outcome, and NLR combined with Fisher grade significantly improves the prediction of rebleeding following aSAH.

19.
J Surg Res ; 251: 180-186, 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32155473

RESUMO

OBJECTIVE: To explore the distribution of biliary ductules in biliary remnants of patients with biliary atresia and to investigate the relationship between the ductules and the prognosis after Kasai portoenterostomy. PATIENTS AND METHODS: From October 01, 2015 to September 30, 2017, 46 patients who were diagnosed as type 3 biliary atresia were enrolled in this study. Continuous sections of biliary remnants were stained with cytokerantin 19 antibody. The number, area, and distribution of micro-biliary ductules of each section were recorded. According to the number of ductules in the most proximal section (n ≥ 20 or n < 20), patients were divided into two groups (A or B) and followed up for 1-3 y, including cholangitis, jaundice clearance, and survival with native liver. RESULTS: Four patients had no micro-biliary ductules. In 17 patients with ductules, the numbers at bilateral parts were similar (P > 0.05), while the ductules in the middle part were significantly less than bilateral parts (P < 0.05). Starting from 2 mm from the proximal end of remnants, the number of ductules significantly and gradually decreased (P < 0.05). The total area of ductules in Group A was significantly increased compared to that in Group B (P < 0.05). Patients in Group A had significantly higher jaundice clearance rate and better survival rate with native liver than patients in Group B (both, P < 0.05). Patients had significantly higher incidence of cholangitis in Group A compared to Group B (P < 0.05). CONCLUSIONS: The number/area of ductules yielded by technical precision is closely related to effective bile drainage, jaundice clearance, and first onset of cholangitis in patients after Kasai procedure.

20.
Echocardiography ; 37(2): 207-214, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32003075

RESUMO

PURPOSE: To explore endothelial function and plasma matrix metalloproteinase-2 levels and their association with the size and elastic properties of the ascending aorta in the first-degree relatives (FDRs) with tricuspid aortic valve (TAV) of individuals with bicuspid aortic valve (BAV). METHODS: Twenty-six patients with BAV without significant valvular dysfunction, 35 FDRs with TAV, and 29 matched healthy controls were analyzed. Two-dimensional echocardiography and high-resolution ultrasound were applied to evaluate the size and elasticity of the ascending aorta and the flow-mediated vasodilation (FMD) of the brachial artery in response to hyperemia. RESULTS: The aortic diameter was larger in the BAV patients than in the FDRs and controls, and the aortic elastic properties showed larger decreases in the BAV patients. The FDRs had a larger aortic diameter and more impaired elastic properties than the controls. The BAV patients had a significantly lower FMD than the FDRs and controls (P < .001), while the FMD was lower in the FDRs than in the controls (P < .001). The plasma MMP-2 levels were significantly higher in the BAV patients than in the FDRs (P = .001) and controls (P < .001). Additionally, the FDRs had higher plasma MMP-2 levels than the controls (P < .001). Pearson correlation analysis revealed that the aortic diameter, distensibility, stiffness index, and strain were significantly associated with FMD and plasma MMP-2 levels. CONCLUSION: Aortic enlargement and impaired elasticity in the FDRs with TAV were associated with impaired endothelial function and increased plasma MMP-2 concentrations.

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