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1.
Br J Haematol ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31696939

RESUMO

Donor selection for older leukaemia patients undergoing haematopoietic cell transplant (HCT) is not well defined: outcomes might be improved with a younger offspring donor rather than an older human leukocyte antigen (HLA)-matched sibling donor (MSD). We extended our multicentre dataset. A total of 185 acute leukaemia patients (≥ 50 years) transplanted in first complete remission who received HCT from offspring (n = 62) or MSD (n = 123) were included. A 1:1 ratio matched-pair analysis was performed. We were able to match 54 offspring with 54 MSD patients. Outcomes were compared between the two matched-pair groups. The cumulative incidence of grade II/IV acute graft-versus-host disease (GVHD) (26% vs. 35%; P = 0·23) and chronic GVHD (37% vs. 24%; P = 0·19) was comparable between groups (MSD vs. offspring). The lower three-year transplant-related mortality (9% vs. 26%; P = 0·023) and relapse incidence (6% vs. 17%; P = 0·066) resulted in higher overall survival (85% vs. 58%; P = 0·003) and leukaemia-free survival (LFS) (85% vs. 56%; P = 0·001) in offspring HCT compared with that in MSD HCT. These data might favour a young offspring over an older MSD in patients >50 years. The current analyses confirm that non-HLA donor characteristics, such as kinship and donor age, rather than HLA disparity, predominantly influence survival in older acute leukaemia patients.

2.
EBioMedicine ; 49: 213-222, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31668569

RESUMO

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) after allo-HSCT is a devastating complication with limited therapeutic options. We aimed to assess the efficacy and safety of mesenchymal stem cells (MSCs) in BOS after allo-HSCT. METHODS: This multicenter prospective cohort study enrolled 81 allo-HSCT recipients whose BOS were diagnosed within 6 months. The choice of prednisone and azithromycin combined with or without MSCs was based on patient preferences (MSC n = 49, non-MSC n = 32). The primary endpoint was response rate at 3 months, defined as the proportion of patients achieving FEV1 improvement or steroid sparing. The trial was registered at ClinicalTrials.gov (NCT02543073). FINDINGS: Response rate was 35/49 patients (71%, 95% CI 59 to 84%) and 14/32 (44%, 27 to 61%) in MSC and non-MSC group, respectively (p = 0.013). The addition of MSCs was associated with a better difference for change in FEV1 rate of decline, compared to non-MSC group (53 mL/months, 2 to 103; p = 0.040). The 3-year overall survival post-diagnosis was 70.6% (55.9 to 85.3%) and 58.2% (36.1 to 78.5%) in MSC and non-MSC group, respectively (p = 0.21). Clinical improvement was accompanied by a significant increase of interleukin (IL)-10-producing CD5+B cells. There was no statistical difference in the rates of infections and leukemia relapse between the two groups. MSCs were well-tolerated with no serious adverse events. INTERPRETATION: MSCs offer an effective and safe therapeutic option for BOS after allo-HSCT. Our study strengthens evidence for clinical use of MSC therapy in BOS. These data also provide novel insight into potential biological mechanisms of MSC treatment and support further investigation in larger randomized controlled trials. FUNDING: National Key R&D Program of China, National Natural Science Foundation of China, Health Collaborative Innovation Major Projects of Guangzhou City, Science and Technology Planning Project of Guangdong Province.

3.
Resuscitation ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31756360

RESUMO

BACKGROUND: Dispatcher-assisted cardiopulmonary resuscitation (DACPR) could improve the survival rate of out-of-hospital cardiac arrest (OHCA). However, the efficiency of DACPR varies. Our study compared the effectiveness of DACPR instructed via landline calls, mobile calls, and landline calls transferred to mobiles. METHOD: This prospective cohort study enrolled patients with OHCA between 1 July 2017 and 30 November 2018 in Taichung. Patients were divided into a mobile group and a landline group according to device used to call emergency medical services (EMS). The landline group was subdivided according to whether the call was transferred to a mobile. We compared the DACPR rate and call to chest compression time between groups. RESULTS: The study comprised 2404 cases after exclusion: 934 cases of DACPR via mobile and 1470 via landline. In the mobile group, DACPR rate (54% vs. 47.5%, P < 0.001) was higher and call to chest compression time (median: 156 s vs. 174 s P < 0.001) was shorter than in the landline group. In the transferred group, DACPR rate (72.7% vs. 28.8%, P < 0.001) was higher than in the non-transferred group, but no difference was observed in call to chest compression time (median: 173 s vs. 177 s, P = 0.69). CONCLUSION: According to this city-based prospective clinical study, communication over mobiles resulted in higher DACPR rate and shorter call to chest compression time than that over landlines. Transferring calls from a landline to a mobile could increase the DACPR rate without delaying the initiation of chest compression.

4.
Sci Total Environ ; 703: 134720, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31731171

RESUMO

Phenols and parabens are endocrine-disrupting chemicals and are widely used in daily life products due to their antibacterial action. Previous studies suggest associations of prenatal exposure to phenols and parabens with fetal development; however, such findings are rare and inconsistent. The aim of this review and meta-analysis is to estimate the associations between maternal exposure to phenols and parabens and birth size. We identified 21 relevant studies that met the inclusion criteria through databases of PubMed, Cochrane, EMBASE and Qvid Medline. The last search was in July 3, 2019. The heterogeneity and possibility of publication bias among included studies were assessed by Q-statistic and Begg's test, respectively. Meta-analysis revealed that prenatal exposure to triclosan [number of studies (n) = 12, regression coefficient (ß) = -0.04 g; 95% confidence interval (CI): -0.139, 0.059], benzophenone-3 (n = 10, ß = -0.001 g; 95% CI: -0.013, 0.012), bisphenol A (n = 9, ß = -0.049 g; 95% CI: -0.199, 0.101), 2-4-dichlorophenols (n = 6, ß = -14.124 g; 95% CI: -29.971, 1.723), 2-5-dichlorophenols (n = 6, ß = -0.061 g; 95% CI: -0.196, 0.074) and parabens were negatively associated with fetal birth weight. Most of them were insignificant. Inconsistent and insignificant associations were detected between exposure to phenols and parabens and other birth outcomes. Subgroup analysis suggested that heterogeneity in our meta-analysis was mainly attributed to the studies conducted in developed countries and samples collected in the second trimester. Insignificant and controversial associations of maternal exposure to phenols and parabens with birth size were observed in our study. The study design and methods of the included studies are inconsistent, and the effects of environmental pollutants on human health are complex. Further cohort studies with large samples and a consistent approach are thus required to evaluate the associations of maternal exposure to phenols and parabens with birth size.

5.
Biol Trace Elem Res ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31637582

RESUMO

The exposure to endocrine disruptors and the disruption of the circadian rhythms can both affect thyroid hormones, with results that are most likely carcinogenic in humans. The effects of cadmium (Cd) level and circadian-related single-nucleotide polymorphisms (SNPs) on thyroid cancer (TC) risk have rarely been reported. In this study, the associations of urine Cd, CLOCK gene polymorphisms, and TC risk were evaluated, in addition to the effect of the gene-environment interaction on TC risk. In this case-control study, 218 TC cases and 218 controls were enrolled. Cd in urinary samples was determined by atomic absorption spectrometry. Three SNPs (rs3805151, rs3805154, and rs78929565) were genotyped with an improved multiplex ligation detection reaction technique. The individuals with a high Cd level were 1.72-fold more likely to have TC (OR = 1.72, 95%CI 1.04-2.85), and a high Cd level was associated with higher tumor T stage and N stage (OR = 2.42, 95%CI 1.28-4.58; OR = 3.26, 95%CI 1.67-6.33, respectively). Individuals with TT genotype of rs78929565 had a 107 % increase in TC risk (OR = 2.07, 95%CI 1.00-4.29). Cases with CT genotype tended to have a higher AJCC stage (OR = 2.79, 95% CI 1.01-7.78). A significant interaction was detected between the rs78929565 variant and Cd exposure (p interaction = 0.04). The TT genotype carriers of rs78929565 with a high Cd level were more susceptible to thyroid cancer than the major homozygotes carriers who were exposed to a low cadmium level (OR = 2.66, 95%CI 1.07-6.59). These findings suggested that Cd exposure and the CLOCK variant genotypes were associated with TC risk and tumor severity. Individuals with minor allele of rs78929565 and higher Cd exposure had increased susceptibility to TC. Further studies are required to confirm these findings.

6.
PLoS One ; 14(9): e0222338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31527891

RESUMO

Rhesus macaque is an important animal model in biomedical research, especially human disease, developmental, translational, and pre-clinical research. Blood physiological and biochemical parameters are important markers for physiology, pathology, and toxicology research. However, these parameters have not been systematically reported for Chinese rhesus macaques. To characterize the reference for these parameters, this study collected 1805 Chinese rhesus macaques living in Southwestern China. A total of 24 blood physiological indexes and 27 biochemical parameters were determined. Sex and age were found to affect these parameters. In conclusion, a comprehensive and systematic reference of hematological and biochemical parameters for Chinese rhesus macaque was established in this work on the basis of a large cohort. Such reference will benefit biomedical research employing rhesus macaques as animal models.

7.
Cancer Med ; 8(15): 6549-6558, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31502764

RESUMO

To investigate the incidence and risk factors as well as prognosis of autoimmune hemolytic anemia (AIHA) following allogeneic hematopoietic stem cell transplantation (allo-HSCT), a total of 1377 adult hematological malignancies at three institutions were enrolled in this study. The 3-year cumulative incidence of AIHA was 2.2 ± 0.4%. Multivariate analysis showed that haploidentical donors (HRDs) and chronic graft vs host disease (cGVHD) were the independent risk factors for AIHA. Patients with AIHA treated initially with corticosteroids combined with cyclosporine A (CsA) had a higher complete response rate than those with corticosteroids monotherapy (66.7% vs 11.1%; P = .013). The 3-year cumulative incidence of malignant diseases relapse was 4.4 ± 4.3% and 28.0 ± 1.3% (P = .013), treatment-related mortality (TRM) was 8.9 ± 6.3% and 17.4 ± 1.2% (P = .431), disease-free survival (DFS) was 56.1 ± 1.5% and 86.7 ± 7.2% (P = .011), and overall survival (OS) was 86.3 ± 7.4% and 64.1 ± 1.5% (P = .054), respectively, in the patients with AIHA and those without AIHA. Our results indicate that HRDs and cGVHD are risk factors for AIHA and corticosteroids combined with CsA are superior to corticosteroids as initial treatment for AIHA. Autoimmune hemolytic anemia does not contribute to increase TRM and could reduce the malignant diseases relapse and increase DFS.

8.
J Hematol Oncol ; 12(1): 88, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481121

RESUMO

BACKGROUND: Low-dose post-transplant cyclophosphamide (PTCy) in conjunction with anti-thymocyte globulin (ATG) appears as a potentially effective graft-versus-host disease (GVHD) prevention strategy in haploidentical hematopoietic cell transplant (haplo-HCT). Our study aims to assess the efficacy of this regimen. METHODS: We extended our prospective study in patients treated with low-dose PTCy (14.5 mg/kg on days 3 and 4) in ATG/granulocyte colony-stimulating factor (G-CSF)-based regimen and compared the results to the contemporary cohort of patients without low-dose PTCy (ATG cohort). Both study cohort and control are transplanted from maternal donor or collateral relatives. RESULTS: We identified 239 consecutive patients (ATG-PTCy cohort = 114; ATG cohort = 125). All patients but one in ATG cohort achieved myeloid engraftment by day 30 post-HCT. We found that both the cumulative incidence of 100-day grade III-IV aGvHD and non-relapse-mortality (NRM) in the ATG-PTCy cohort was significantly reduced than that in the ATG group (5% vs 18%; P = 0.003; and 6% vs 15%; P= 0.045); the 2-year cumulative incidences of relapse and overall survival were comparable between the two cohorts (13% vs 14%; P = 0.62; and 83% vs 77%; P = 0.18, respectively). Furthermore, GVHD-free, relapse-free survival (GRFS) was significantly improved in the ATG-PTCy arm (63% vs 48%; P = 0.039). In multivariate analysis, the joint treatment resulted in lower grade II-IV acute GVHD (HR 0.58; P = 0.036), grade III-IV aGvHD (HR 0.28; P = 0.006), chronic GVHD (HR 0.60; P = 0.047), NRM (HR 0.26; P = 0.014), and higher GRFS (HR 0.59; P = 0.021) but slower myeloid and platelet recovery (HR 0.29 and 0.30; both P < 0.001). CONCLUSIONS: These results suggested that ATG/PTCy (low-dose) can reduce both acute and chronic GVHD as compared with standard ATG-based prophylaxis using maternal donor or collateral relatives at particular high GVHD risk.

9.
Arch Environ Contam Toxicol ; 77(4): 490-500, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31363802

RESUMO

Metals from the natural environment have potential hypertension effects. However, relevant studies on this topic are few. A total of 1358 adults aged 18-74 years from Chizhou, Maanshan, and Tongling of Anhui Province participated in the baseline study from 2014 to 2015. The follow-up study was performed from 2016 to 2017. Inductively coupled plasma optical emission spectrometry (7000 DV) was used to measure urinary Cr, Mn, Fe, Cu, and Zn of residents. Urinary concentrations of Cd determined via TAS-900 atomic absorption spectrophotometry at 228.8 nm wavelength. A total of 275 hypertension cases were identified. After adjusting for sociodemographic factors and risk factors for hypertension, four metals (Cd, Cr, Cu, and Mn) were significantly associated with hypertension in the single-metal model. Upon including all metals in the same model, the hazard ratios of the highest quartiles Cd and Cu compared with the reference group were 1.42 (95% confidence interval [CI] 1.09-2.02) and 1.56 (95% CI 1.16-2.09) for cases of hypertension. Our findings suggested that high levels of Cd and Cu might increase the incidence of hypertension. Further studies involving larger population should be conducted to confirm these findings.

10.
Clin Pharmacol Ther ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31437302

RESUMO

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) regulates inflammation, cytokine release, and necroptotic cell death and is implicated in pathogenic cellular pathways in amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and multiple sclerosis. Inhibition of RIPK1 activity protects against inflammation and cell death in multiple animal models. DNL104 is a selective, brain-penetrant inhibitor of RIPK1 phosphorylation in clinical development for AD and ALS. DNL104 was tested in 68 healthy volunteers to investigate safety and tolerability, pharmacokinetic profile in plasma and cerebrospinal fluid, and pharmacodynamic effects of RIPK1 inhibition in peripheral blood mononuclear cells in a first-in-human, placebo-controlled, double-blind, randomized single-ascending dose (SAD) and multiple-ascending dose (MAD) study. DNL104 was well-tolerated in the SAD group and during the dosing period of the MAD group. However, postdose liver toxicity in 37.5% of subjects was observed in the MAD, and assessed to be drug related. We demonstrate that DNL104 leads to RIP1 kinase inhibition, and this is not associated with central nervous system (CNS) toxicities, supporting future development of CNS penetrant RIPK1 inhibitors.

11.
BMC Med ; 17(1): 156, 2019 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-31401973

RESUMO

BACKGROUND: The optimal dose of rabbit antithymocyte globulin (ATG, ImtixSangstat) minimizing infections without increasing graft-versus-host disease (GVHD) is unknown in T cell-replete, G-CSF-primed haploidentical hematopoietic stem cell transplantation (haplo-HSCT). METHODS: Four hundred and eight patients were enrolled in this multicenter study to evaluate the effect of 7.5 mg/kg and 10.0 mg/kg rabbit ATG on viral infections and GVHD prophylaxis after haplo-HSCT. The primary endpoint was EBV DNAemia within 1 year posttransplantation. RESULTS: The 1-year incidence of EBV DNAemia was 20.7% (95% confidence interval, 15.4-26.5) and 40.0% (33.3-46.6) in the 7.5 mg/kg and 10.0 mg/kg groups, respectively (P < 0.001). The 100-day cumulative incidence of grade II to IV aGVHD was 27.1% (21.1-33.4) and 25.4% (19.6-31.5) in the 7.5 mg/kg and 10.0 mg/kg ATG groups, respectively (P = 0.548). The 2-year incidence of chronic GVHD was 34.6% (27.8-41.4) and 36.2% (29.1-43.2) in the 7.5 mg and 10.0 mg groups (P = 0.814). The 1-year incidence of CMV DNAemia was 73.4% (67.2-79.4) and 83.4% (77.5-87.9) in the 7.5 mg/kg and 10.0 mg/kg groups (P = 0.038). The 3-year overall survival posttransplantation was 69.5% (63.2-75.8) and 63.5% (56.2-70.8), and the disease-free survival was 62.2% (55.3-69.1) and 60.3% (53.0-67.6) in the 7.5 mg/kg and 10.0 mg/kg groups, respectively (OS: P = 0.308; DFS: P = 0.660). The counts of EBV- and CMV-specific cytotoxic T cells (CTLs) were higher in the 7.5 mg/kg group than in the 10.0 mg/kg group early posttransplantation. CONCLUSIONS: Compared with 10.0 mg/kg, 7.5 mg/kg ATG for GVHD prophylaxis was associated with reduced EBV and CMV infections without increased incidence of GVHD in haplo-HSCT, probably by affecting EBV- and CMV-specific CTLs. TRIAL REGISTRATION: clinicaltrials.gov, NCT01883180 . Registered 14 June 2013.

12.
Biol Blood Marrow Transplant ; 25(10): 1944-1955, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31299215

RESUMO

The intestinal microbiome plays an important role in the development of acute graft-versus-host disease (aGVHD). However, whether intestinal microbiota can predict the development of aGVHD has been reported only rarely. Here we conducted a prospective study of microbiota in 141 patients after allogeneic hematopoietic stem cell transplantation. We found lower microbiota diversity in the aGVHD group compared with the non-aGVHD group at day 0 and day 15 ± 1 (P = .018 and .009, respectively). Diversity was negatively associated with conditioning intensity (P = .017, day 0; P = .045, day 15) and ß-lactam antibiotic administration (P = .004, day 15). Intensified conditioning and ß-lactam antibiotics were associated with a lower regulatory T (Treg)/T helper 17 (Th17) cell ratio at day 15 (P = .030 and .047, respectively). At day 15, the levels of the inflammatory factors (tumor necrosis factor α, interleukin [IL]-6, IL-17A, IL-1ß, and lipopolysaccharide) were higher in the intensified conditioning group compared with the standard group (P < .05). The accumulated intestinal microbiota (AIM) score was defined as microbiota diversity and gradient of the 4 bacterials (Lachnospiraceae, Peptostreptococcaceae, Erysipelotrichaceae, and Enterobacteriaceae) at day 15 post-transplantation. The AIM score was positively correlated with aGVHD grade (r = .481, P < .001), and the AIM score could be predictive of the development of aGVHD (grade II-IV aGVHD: area under the curve [AUC], .75, P < .001; grade III-IV aGVHD: AUC, .84, P < .001). These findings suggest that intestinal microbiota and conditioning might induce aGVHD by inflammatory factors and the Treg/Th17 balance. The constitution of the intestinal microbiota at neutrophil engraftment may predict the development of aGVHD.

13.
BMC Med Educ ; 19(1): 199, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196087

RESUMO

BACKGROUND: The shortage of primary care physicians in rural China is an enduring problem with serious implications for access to care. In response to the shortage in health workforce in rural areas, China government has launched the rural-oriented tuition-waived medical education (RTME) programme since 2010, aiming to train more general practitioners to address the rural health workforce requirements in middle and west areas. This study aims to investigate the prevalence of mental illness and the level of professional identity in the rural-oriented tuition-waived medical students (RTMSs), and to explore the impact of the RTMSs' professional identity and related cognition and satisfaction with the RTME programme on mental health. METHODS: We conducted a descriptive, cross-sectional study. A total of 1103 RTMSs and 1095 non-oriented medical students from seven medical universities (colleges) in Anhui province completed a demographic questionnaire, the Depression, Anxiety, Stress Scales and the Professional Identity Questionnaire for Undergraduate Students. Cognition and satisfaction with the RTME programme of the RTMSs were collected. Multiple linear regression analysis was used to analyze the data. RESULTS: The prevalence of depression, anxiety, and stress in RTMSs were 11.8, 22.9 and 3.4%, respectively. The mean total scores of the Professional Identity Questionnaire for Undergraduate Students were 3.58 (SD = 0.61). Results of multiple linear regression model indicated that students who are dissatisfied with targeted primary healthcare institution are likely to suffer from depression and anxiety; moreover, students who enrolled in the rural-oriented tuition-waived medical education programme due to economic reason are more likely to suffer from anxiety. Furthermore, a significant positive correlation was found between professional identity and mental health. CONCLUSIONS: Providing better information about the RTME programme prior to enrollment and improving the students' cognition of the policy's effectiveness and the social value of rural healthcare work may contribute to improving the professional identity of the RTMSs. Meanwhile, a significant positive association was found between professional identity and mental health. This is a new perspective that shows that developing and improving professional identity may help medical students reduce the risk of psychological illness.

14.
Viruses ; 11(5)2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31108901

RESUMO

Worldwide, the Hepatitis E virus (HEV) is the main pathogen of acute viral hepatitis, with an extremely high mortality in pregnant women. However, the pathogenesis of HEV infection in pregnant women remains largely unknown. We established an HEV-infected pregnant mice animal model to explore the adverse pregnancy outcomes of HEV infection. Mice were infected with HEV in their early, middle and late stages of pregnancy. HEV RNA was detected in the tissues (liver, spleen, kidney, colon, uterus and placenta) of pregnant mice. HEV antigens were also detected in these tissues of HEV-infected pregnant mice. Miscarriages (7/8, 87.5%) occurred in pregnant mice infected with HEV in the middle of pregnancy. Th1-biased immune status was found in these aborted mice. Vertical transmission was confirmed by HEV replication in the uterus and placenta, as well as in the positive HEV RNA and HEV antigen positive in fetal livers. The successful establishment of HEV infection in pregnant mice is beneficial for further study of HEV pathogenesis, especially the adverse pregnancy outcomes caused by HEV infection.

15.
Environ Sci Pollut Res Int ; 26(20): 20560-20572, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104243

RESUMO

Papillary thyroid cancer (PTC) has inflicted huge threats to the health of mankind. Metal pollution could be a potential risk factor of PTC occurrence, but existing relevant epidemiological researches are limited. The current case-control study was designed to evaluate the relationships between exposure to multiple metals and the risk of PTC. A total of 262 histologically confirmed PTC cases were recruited. Age- and gender-matched controls were enrolled at the same time. Urine samples were used as biomarkers to reflect the levels of environmental exposure to 13 metals. Conditional logistic regression models were adopted to assess the potential association. Single-metal and multi-metal models were separately conducted to evaluate the impacts of single and co-exposure to 13 metals. The increased concentration of urinary Cd, Cu, Fe, and Pb quartiles was found significant correlated with PTC risk. We also found the decreased trends of urinary Se, Zn, and Mn quartiles with the ORs for PTC. These dose-response associations between Pb and PTC were observed in the single-metal model and remained significant in the multi-metal model (OR25-50th=1.39, OR50-75th=3.32, OR>75th=7.62, p for trend <0.001). Our study suggested that PTC was positively associated with urinary levels of Cd, Cu, Fe, Pb, and inversely associated with Se, Zn, and Mn. Targeted public health policies should be made to improve the environment and the recognition of potential risk factors. These findings need additional studies to confirm in other population.


Assuntos
Exposição Ambiental , Poluentes Ambientais/toxicidade , Metais Pesados/toxicidade , Câncer Papilífero da Tireoide/induzido quimicamente , Neoplasias da Glândula Tireoide/induzido quimicamente , Estudos de Casos e Controles , China/epidemiologia , Poluentes Ambientais/urina , Feminino , Humanos , Masculino , Metais Pesados/urina , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Câncer Papilífero da Tireoide/epidemiologia , Câncer Papilífero da Tireoide/urina , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/urina
17.
Environ Toxicol Pharmacol ; 69: 129-136, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31030175

RESUMO

OBJECTIVES: Chronic exposure to arsenic during pregnancy or early life continues to be a major global health problem worldwide, affecting hundreds of millions of people. However, its effects on birth size are uncertain. The aim of this study is to summarized the association between maternal arsenic exposure and birth size. METHODS: A comprehensive literature search was conducted on the maternal arsenic exposure and birth size (birth weight, birth length, head circumference and chest circumference) through databases (PubMed, Qvid Medline, Web of Science, Cochrane and EMBASE), the last search was in March 2019. Heterogeneity was testes by using the Q statistic and stratifying for epidemiological factors. The possibility of publication bias was assessed through Begg's test. RESULTS: A total of 12 studies provided sufficient data were included. Meta-analysis revealed that maternal arsenic exposure was associated with the decrease of birth weight (ß = -25.0 g; 95% CI: -41.0, -9.0) and head circumference (ß = -0.12 cm; 95% CI: -0.24, -0.01) in random-effect model, birth length (ß = -0.12 cm; 95% CI: -0.17, -0.07) in fixed-effect model, no significant reduction was suggested in chest circumference (ß = -0.74 cm; 95% CI: -1.78, 0.3). In addition, we found that the birth weight decreased stronger in women living in the Americas, or appling the exposure marker of urine. CONCLUSIONS: Maternal arsenic exposure is associated with the decrease of the birth weight, length and head circumference. Millions of people are still exposured to high-level arsenic, therefore, high quality epidemiologic studies that involve large samples are necessary to determine the precise relationships between maternal arsenic exposure with birth size. And that effective mitigation measures are also need to prevent arsenic exposure in women of reproductive age.


Assuntos
Arsênico/toxicidade , Tamanho Corporal/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Exposição Materna/efeitos adversos , Feminino , Humanos , Recém-Nascido , Troca Materno-Fetal , Gravidez
18.
Biol Blood Marrow Transplant ; 25(8): 1674-1681, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31009704

RESUMO

The optimal therapy for patients with acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) who relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. In this study we retrospectively evaluated the efficacy of sorafenib combined with other therapeutic strategies as salvage therapy for these patients. Eighty-three AML patients with FLT3-ITD relapsing after allo-HSCT were enrolled in this study. Fifty-three patients received salvage therapy containing sorafenib and 30 patients did not. Salvage therapy containing sorafenib was superior to that without sorafenib with respect to complete remission rates, overall survival (OS), and progression-free survival (PFS) (66.0% versus 30.0%, 46.8% versus 20.0%, and 44.9% versus 16.7%, respectively; P = .002, P = .003, and P = .001). Further subgroup analysis revealed that the OS and PFS of patients who received sorafenib combined with chemotherapy followed by donor lymphocyte infusion (DLI) were superior to those receiving other therapeutic regimens, including sorafenib combined with chemotherapy, chemotherapy followed by DLI, and monochemotherapy (P = .003, P < .001). Multivariate analysis revealed that salvage therapy including sorafenib was the only protective factor for longer OS (P = .035; hazard ratio [HR], .526); salvage therapy including sorafenib and DLI were the protective factors for longer PFS (P = .011, HR, .423; P = .019, HR, .508). Our data suggest that sorafenib therapy is associated with improved outcomes for FLT3-ITD AML relapsing after allo-HSCT, and whether sorafenib combined with chemotherapy followed by DLI reveals an optimal efficacy merits further study.

19.
J Autoimmun ; 100: 95-104, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30878167

RESUMO

Chronic graft-versus-host disease (cGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have shown that T follicular helper cells (Tfh) contribute to immune pathology in cGVHD, but the function of extrafollicular helper T cells during cGVHD pathogenesis remains largely unknown. In the current study, we identified circulating extrafollicular helper T-like cells (CD44hiCD62LloPSGL-1loCD4+, c-extrafollicular Th-like) in human peripheral blood. We performed phenotypic and functional analyses of c-extrafollicular Th-like cells from 80 patients after allo-HSCT to explore the role of these cells in the development of human cGVHD. Patients with active cGVHD had significantly higher frequencies and counts of c-extrafollicular Th-like cells than those of patients without cGVHD. The expansion of c-extrafollicular Th-like cells was more significant in patients with moderate/severe cGVHD than that of patients with mild cGVHD. C-extrafollicular Th-like cells from patients with active cGVHD exhibited increased functional abilities to induce plasmablast differentiation and IgG1 secretion compared to those of patients without cGVHD. Moreover, c-extrafollicular Th-like cell levels were highly correlated with the generation of autoreactive B cells, plasmablasts and IgG1 antibodies. Our studies provide new insights into human cGVHD pathogenesis and identify c-extrafollicular Th-like cells as a key element in the development of human cGVHD.

20.
Resuscitation ; 138: 106-109, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30862425

RESUMO

BACKGROUND: In Taiwan, emergency department (ED) crowding is inevitable; many studies have investigated the various negative effects of ER crowding on patients. In general, ED crowding reduces patient satisfaction, delays treatment, and increases mortality. However, most studies have focused on the relationship between ED crowding and delay mortality rather than sudden mortality. This study investigates the association of ED crowding with sudden unexpected in-hospital cardiac arrest (IHCA). METHODS: The retrospective observational study recruited patients with sudden IHCA in an ED from February 2016 to September 2017. Exclusion criteria included (1) out-of-hospital cardiac arrest, (2) patient with signed do-not-resuscitate consent, (3) pediatric patient, and (4) trauma patient. ED crowding parameters, including ED bed occupancy rates (EDBORs), number of boarding patients, and patients with boarding time to general ward or intensive care unit of >24 and >48 h, all were recorded every 2 h. RESULTS: Significant increments were noted in IHCA incidence when EDBOR was >260%, with a rate ratio of 1.50 (95% confidence interval [CI], 1.03-2.17). However, the number of boarding patients was not associated with IHCA incidence (P > 0.05). Prolonged boarding time to general ward and ICU of >24 and >48 h both increased the IHCA incidence. CONCLUSION: This first study investigating the relationship between ED crowding and sudden IHCA found EDBORs and prolonged boarding to general wards or ICUs were associated with increased sudden IHCA incidence.

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