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1.
Am J Hum Genet ; 106(2): 264-271, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32004448

RESUMO

Severe aplastic anemia (SAA) is a rare disorder characterized by hypoplastic bone marrow and progressive pancytopenia. The etiology of acquired SAA is not understood but is likely related to abnormal immune responses and environmental exposures. We conducted a genome-wide association study of individuals with SAA genetically matched to healthy controls in discovery (359 cases, 1,396 controls) and validation sets (175 cases, 1,059 controls). Combined analyses identified linked SNPs in distinct blocks within the major histocompatibility complex on 6p21. The top SNP encodes p.Met76Val in the P4 binding pocket of the HLA class II gene HLA-DPB1 (rs1042151A>G, odds ratio [OR] 1.75, 95% confidence interval [CI] 1.50-2.03, p = 1.94 × 10-13) and was associated with HLA-DP cell surface expression in healthy individuals (p = 2.04 × 10-6). Phylogenetic analyses indicate that Val76 is not monophyletic and likely occurs in conjunction with different HLA-DP binding groove conformations. Imputation of HLA-DPB1 alleles revealed increased risk of SAA associated with Val76-encoding alleles DPB1∗03:01, (OR 1.66, p = 1.52 × 10-7), DPB1∗10:01 (OR 2.12, p = 0.0003), and DPB1∗01:01 (OR 1.60, p = 0.0008). A second SNP near HLA-B, rs28367832G>A, reached genome-wide significance (OR 1.49, 95% CI 1.22-1.78, p = 7.27 × 10-9) in combined analyses; the association remained significant after excluding cases with clonal copy-neutral loss-of-heterozygosity affecting class I HLA genes (8.6% of cases and 0% of controls). SNPs in the HLA class II gene HLA-DPB1 and possibly class I (HLA-B) are associated with SAA. The replacement of Met76 to Val76 in certain HLA-DPB1 alleles might influence risk of SAA through mechanisms involving DP peptide binding specificity, expression, and/or other factors affecting DP function.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32060638

RESUMO

OBJECTIVE: Coal miners are exposed to polycyclic aromatic hydrocarbons (PAHs), a group of neurotoxicants formed and released during incomplete combustion of coal. High levels of anxiety and depression have been reported in coal miners, but little is known about neurobehavioral functions in populations that are occupationally exposed to PAHs. We tested neurobehavioral performance in coal miners and correlated it with levels of urinary markers of PAH exposure. METHODS: Levels of urinary PAH metabolites were measured in 652 male coal miners as an indicator of exposure. Subjects were divided into a high-exposure group and a low-exposure group based on the median level of total PAH metabolites. A neurobehavioral core test battery and a questionnaire were used to assess neurobehavioral performance and collect demographic information, respectively. RESULTS: The median level of total PAH metabolites in urine was 4.88 µmol/mol creatinine. Highly exposed workers exhibited more fatigue-inertia than less-exposed workers (p < 0.05), and had lower scores in forward digit span, digit symbol, and Benton visual retention tests (p < 0.05). Multiple linear regression indicated that age, education, and shift work were significantly correlated with test scores. CONCLUSIONS: PAH exposure may be associated with neurobehavioral alterations, which should be monitored in coal miners to prevent neurobehavioral disorders.

3.
J Surg Res ; 250: 45-52, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32018142

RESUMO

BACKGROUND: The Model for End-Stage Liver Disease Sodium (MELD-Na) incorporates hyponatremia into the MELD score and has been shown to correlate with surgical outcomes. The pathophysiology of hyponatremia parallels that of ascites, which purports greater surgical risk. This study investigates whether MELD-Na accurately predicts morbidity and mortality in patients with ascites undergoing general surgery procedures. MATERIALS AND METHODS: We used the National Surgical Quality Improvement Program database (2005-2014) to examine the adjusted risk of morbidity and mortality of cirrhotic patients with and without ascites undergoing inguinal or ventral hernia repair, cholecystectomy, and lysis of adhesions for bowel obstruction. Patients were stratified by the MELD-Na score and ascites. Outcomes were compared between patients with and without ascites for each stratum using low MELD-Na and no ascites group as a reference. RESULTS: A total of 30,391 patients were analyzed. Within each MELD-Na stratum, patients with ascites had an increased risk of complications compared with the reference group (low MELD-Na and no ascites): low MELD-Na with ascites odds ratio (OR) 4.33 (95% confidence interval [CI] 1.96-9.59), moderate MELD-Na no ascites OR 1.70 (95% CI 1.52-1.9), moderate MELD-Na with ascites OR 3.69 (95% CI 2.49-5.46), high MELD-Na no ascites OR 3.51 (95% CI 3.07-4.01), and high MELD-Na ascites OR 7.18 (95% CI 5.33-9.67). Similarly, mortality risk was increased in patients with ascites compared with the reference: moderate MELD-Na no ascites OR 3.55 (95% CI 2.22-5.67), moderate MELD-Na ascites OR 13.80 (95% CI 5.65-33.71), high MELD-Na no ascites OR 8.34 (95% CI 5.15-13.51), and high MELD-Na ascites OR 43.97 (95% CI 23.76-81.39). CONCLUSIONS: MELD-Na underestimates morbidity and mortality risk for general surgery patients with ascites.

4.
Cancer Med ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31994324

RESUMO

PURPOSE: The proportion of cured gastric cancer patients has drawn the attention of patients, physicians, and healthcare providers after comprehensive prevention and control measures were carried out for several years. Therefore, the relative survival and cure fraction were estimated in our study. METHODS: Population-based cancer registration data were used to estimate survival and cure fraction. A total of 7585 gastric cancer cases (ICD10:C16.0 ~ C16.9) were extracted and included in the final analysis. Cases were diagnosed in 2003-2012 and followed until the end of 2017. Relative survival was calculated as the ratio between the observed survival through the life-table method. The expected survival was estimated by the Ederer II method. The cure fraction was estimated using flexible parametric cure models stratified by age and calendar period when the cases were diagnosed. RESULTS: The 5-year relative survival of cardia gastric cancer increased with the calendar period of 2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2012 (27.5%, 28.3%, 33.5%, 38.2%, and 46.8%, respectively). The increasing trend along with the calendar periods was also observed in cure proportion of cardia gastric cancer (24.8%, 25.2%, 31.7%, 36.0%, and 43.1%, respectively). Notable improvement of cure proportion was observed in the period of 2011-2012, compared with the initial period of 2003-2004. There was an improvement of 79.8% among all gastric cancer subjects, and it was 74.1% and 55.7% in cardia gastric and noncardia gastric cancer subjects, respectively. The median survival of "uncured" patients showed no significant improvement along with the calendar periods in all age groups. CONCLUSIONS: Notable improvement of gastric cancer relative survival and cure proportion was observed in Linzhou during 2003-2012.

5.
Environ Health Perspect ; 128(1): 17006, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31909654

RESUMO

BACKGROUND: Both extreme heat and air pollution exposure during pregnancy have been associated with preterm birth; however, their combined effects are unclear. OBJECTIVES: Our goal was to estimate the independent and joint effects of heatwaves and fine particulate matter [PM <2.5µm in aerodynamic diameter (PM2.5)], exposure during the final gestational week on preterm birth. METHODS: Using birth registry data from Guangzhou, China, we included 215,059 singleton live births in the warm season (1 May-31 October) between January 2015 and July 2017. Daily meteorological variables from 5 monitoring stations and PM2.5 concentrations from 11 sites were used to estimate district-specific exposures. A series of cut off temperature thresholds and durations (2, 3, and 4 consecutive d) were used to define 15 different heatwaves. Cox proportional hazard models were used to estimate the effects of heatwaves and PM2.5 exposures during the final week on preterm birth, and departures from additive joint effects were assessed using the relative excess risk due to interaction (RERI). RESULTS: Numbers of preterm births increased in association with heatwave exposures during the final gestational week. Depending on the heatwave definition used, hazard ratios (HRs) ranged from 1.10 (95% CI: 1.01, 1.20) to 1.92 (1.39, 2.64). Associations were stronger for more intense heatwaves. Combined effects of PM2.5 exposures and heatwaves appeared to be synergistic (RERIs>0) for less extreme heatwaves (i.e., shorter or with relatively low temperature thresholds) but were less than additive (RERIs<0) for more intense heatwaves. CONCLUSIONS: Our research strengthens the evidence that exposure to heatwaves during the final gestational week can independently trigger preterm birth. Moderate heatwaves may also act synergistically with PM2.5 exposure to increase risk of preterm birth, which adds new evidence to the current understanding of combined effects of air pollution and meteorological variables on adverse birth outcomes. https://doi.org/10.1289/EHP5117.

6.
Environ Res ; 182: 109013, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31918310

RESUMO

Emerging studies have provided evidence on the carcinogenicity of radiofrequency radiation (RFR) from cell phones. This study aims to test the genetic susceptibility on the association between cell phone use and thyroid cancer. Population-based case-control study was conducted in Connecticut between 2010 and 2011 including 440 thyroid cancer cases and 465 population-based controls with genotyping information for 823 single nucleotide polymorphisms (SNPs) in 176 DNA genes. We used multivariate unconditional logistic regression models to estimate the genotype-environment interaction between each SNP and cell phone use and to estimate the association with cell phone use in populations according to SNP variants. Ten SNPs had P < 0.01 for interaction in all thyroid cancers. In the common homozygote groups, no association with cell phone use was observed. In the variant group (heterozygotes and rare homozygotes), cell phone use was associated with an increased risk for rs11070256 (odds ratio (OR): 2.36, 95% confidence interval (CI): 1.30-4.30), rs1695147 (OR: 2.52, 95% CI: 1.30-4.90), rs6732673 (OR: 1.59, 95% CI: 1.01-2.49), rs396746 (OR: 2.53, 95% CI: 1.13-5.65), rs12204529 (OR: 2.62, 95% CI: 1.33-5.17), and rs3800537 (OR: 2.64, 95% CI: 1.30-5.36) with thyroid cancers. In small tumors, increased risk was observed for 5 SNPs (rs1063639, rs1695147, rs11070256, rs12204529 and rs3800537), In large tumors, increased risk was observed for 3 SNPs (rs11070256, rs1695147, and rs396746). Our result suggests that genetic susceptibilities modify the associations between cell phone use and risk of thyroid cancer. The findings provide more evidence for RFR carcinogenic group classification.

7.
Transl Oncol ; 13(1): 42-56, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31760268

RESUMO

Colon cancer is the third most commonly diagnosed cancer in the United States. Recent reports have shown that the location of the primary tumor is of clinical importance. Patients with right-sided colon cancers (RCCs) (tumors arising between the cecum and proximal transverse colon) have poorer clinical outcomes than those with left-sided colon cancers (LCCs) (tumors arising between the distal transverse colon and sigmoid colon, excluding the rectum). Interestingly, women have a lower incidence of colon cancer than men, but have a higher propensity for RCC. The reason for this difference is not known; however, identification of sex-specific differences in gene expression by tumor anatomical location in the colon could provide further insight. Moreover, it could reveal important predictive markers for response to various treatments. This study provides a comprehensive bioinformatic analysis of various genes and molecular pathways that correlated with sex and anatomical location of colon cancers using four publicly available annotated data sets housed in the National Center for Biotechnology Information's Gene Expression Omnibus. We identified differentially expressed genes in tumor tissues from women with RCC, which showed attenuated energy and nutrient metabolism when compared with women with LCC. Specifically, we showed the downregulation of 5' AMP-activated protein kinase alpha subunit (AMPKα) and anti-tumor immune responses in women with RCC. This difference was not seen when comparing tumor tissues from men with RCC to men with LCC. Therefore, women with RCC may have a specific metabolic and immune phenotype which accounts for differences in prognosis and treatment response.

8.
J Antimicrob Chemother ; 75(2): 327-336, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31713615

RESUMO

OBJECTIVES: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) have been increasingly reported in China. Here, a multicentre, longitudinal surveillance study on CR-hvKP is described. METHODS: We retrospectively investigated carbapenem-resistant K. pneumoniae (CRKP) in 56 centres across China during 2015-17 and screened the virulence genes (iucA, iroN, rmpA and rmpA2) for the presence of virulence plasmids. Hypermucoviscosity, serum killing and Galleria mellonella lethality experiments were conducted to identify CR-hvKP among strains with all four virulence genes. Capsule typing, fitness and plasmid features of CR-hvKP were also investigated. RESULTS: A total of 1052 CRKP were collected. Among these, 34.2% (360/1052) carried virulence genes and 72 of them had all four of the virulence genes tested. Fifty-five (76.4%) were considered to be CR-hvKP using the G. mellonella infection model, with KPC-2-producing K64-ST11 being the most common type (80%, 44/55). Prevalence of CR-hvKP differed greatly between regions, with the highest in Henan (25.4%, 17/67) and Shandong (25.8%, 25/97). A significant increase in CR-hvKP among KPC-2-producing ST11 strains was observed, from 2.1% (3/141) in 2015 to 7.0% (23/329) in 2017 (P=0.045). Alarmingly, compared with classic CRKP, no difference in growth was found among CR-hvKP (P=0.7028), suggesting a potential risk for dissemination. The hybrid virulence and resistance-encoding plasmid evolved from pLVPK and the resistance plasmid harbouring blaKPC-2, indicating evolution existed between the hypervirulence and hyper-resistance plasmid. CONCLUSIONS: CR-hvKP were more frequently detected than previously assumed, especially among KPC-2-producing ST11. Dissemination of hypervirulence could be extremely rapid due to limited fitness cost. Also, the evolution of resistance genes into hypervirulence plasmids was identified, presenting significant challenges for public health and infection control.

9.
J Colloid Interface Sci ; 563: 17-26, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31865044

RESUMO

HYPOTHESIS: Eggplant is rich in polysaccharides. The mechanically homogenized eggplant flesh pulp (EFP) is expected to emulsify and stabilize o/w emulsions. The adsorption and network structure of the polysaccharides are hypothesized to contribute to the stability of emulsions. EXPERIMENTS: Creaming index (CI) and droplet size distribution were observed to evaluate the stabilities of EFP emulsions at different EFP concentrations (0.50, 0.75, 1.00, 1.25 and 1.50% w/v). Optical and fluorescence microscopy, confocal laser scanning microscopy and cryogenic scanning electron microscopy were conducted to observe the emulsification properties of the EFP-stabilized emulsions. In addition, rheological measurements were performed to reveal the EFP emulsions' rheological behaviours. FINDINGS: The prepared oil-in-water emulsion emulsified by EFP remained stable at an EFP concentration of 1.50%. Rheological analysis illustrated that the emulsions had typical shear-thinning property and gel-like nature. The emulsification mechanisms were explained by the formation of an interfacial film adhered to the oil droplets and the coherent three-dimensional network formed by filament and sheet-like polysaccharide strands in the continuous phase. This finding may define a new kind of natural and dietary emulsifier for emulsion-based food, beverage, and pharmaceutical products.

10.
J Surg Res ; 245: 81-88, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31404894

RESUMO

BACKGROUND: Delayed emergency department (ED) LOS has been associated with increased mortality and increased hospital length of stay (LOS) for various patient populations. Trauma patients often require significant effort in evaluation, workup, and disposition; however, patient and hospital characteristics associated with increased LOS in the ED for trauma patients remain unclear. METHODS: The Trauma Quality Improvement Project database (2014-2016) was queried for all adult blunt trauma patients. Patients discharged from the ED to the operating room were excluded. Univariate and multivariable linear regression analysis was conducted to identify independent predictors of ED LOS, controlling for patient characteristics (age, gender, race, insurance status), hospital characteristics (teaching status, ACS trauma verification level, geographic region), abbreviated injury scale and comorbid status. RESULTS: 412,000 patients met inclusion criteria for analysis. When controlling for covariates, an increase in age by 1 y resulted in 0.63 increased minutes in the ED (P < 0.001). In multivariable linear regression controlling for injury severity and comorbid conditions, non-white race groups, university status, and northeast region were associated with increased ED LOS. Black and Hispanic patients spent on average 41 and 42 more minutes, respectively, in the ED room when compared with white patients (P < 0.001). Patients seen at University hospitals spent 52 more minutes in the ED when compared with community hospitals, whereas patients at nonteaching hospitals spent 31 fewer minutes (P < 0.001). Patients seen in the Midwest spent the least amount of time in the ED, with patients in the South, West, and Northeast spending 45, 36, and 89 more minutes, respectively (P < 0.001). Non-Medicaid patients at level 1 trauma centers and those requiring intensive care admission had significantly decreased ED LOS. Medicaid patients took the longest to move through the ED with Medicare, BlueCross, and Private insurance outpacing them by 17, 23, and 23 min, respectively (P < 0.001). ACS level 1 trauma centers moved patients through the ED fastest, whereas ACS level II trauma centers and level III trauma centers moved patients through 50 and 130 min slower when compared with ACS level 1 trauma centers (P < 0.001). CONCLUSIONS: ED LOS varied significantly by patient and hospital characteristics. Medicaid patients and those patients at university hospitals were associated with significantly higher ED LOS, whereas ACS trauma verification level status had strong correlation with ED LOS. These results may allow targeted quality improvement programs to enhance ED LOS.

11.
Cancer Lett ; 469: 419-428, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31734356

RESUMO

The role of lncRNAs in the regulation of glutamate metabolism and metabolic reprogramming of pancreatic cancer (PC) during nutrient deprivation is largely unknown. Our study found that alpha-ketoglutarate (aKG) levels were significantly reduced in the absence of XLOC_006390. We subsequently confirmed that the decrease in aKG was mainly due to the downregulation of glutamate dehydrogenase 1 (GDH1) at the mRNA level. Therefore, we first screened transcription factors targeting the GDH1 gene promoter and confirmed that c-Myc regulates GDH1 transcription. c-Myc binds to the promoter of GDH1 and activates its transcription. Downregulation of GDH1 mRNA levels by XLOC_006390 deletion could be rescued by overexpression of c-Myc. Overexpression of XLOC_006390 promoted the protein stability of c-Myc by blocking its ubiquitination. Clinically, XLOC_006390 was positively correlated with the mRNA level of GDH1, and c-Myc positively regulated GDH1 gene expression, which was tightly associated with PC patient prognosis. The dysregulated lncRNA/c-Myc axis increased glutamate metabolism, promoting PC progression to a higher stage. Therefore, XLOC_006390/c-Myc may be a potential target for PC, and its abnormal activation also indicates the progression of PC.

12.
Nat Commun ; 10(1): 5472, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784532

RESUMO

Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31826911

RESUMO

BACKGROUND: Very few previous studies have examined the relationship between thyroid cancer risk and intake of phytoestrogens (PE); furthermore, these studies have reached inconsistent results. METHODS: We analyzed data from a population-based case-control study in Connecticut from 2010 to 2011, including 387 histologically confirmed thyroid cancer cases and 433 population-based controls, with compound data available concerning specific PEs. Multivariate unconditional logistic regression models were used to estimate the associations between specific PEs and the risk of thyroid cancer, adjusting for potential confounders. RESULTS: An elevated risk of thyroid cancer was associated with moderate to high levels of coumestrol intake [OR = 2.48, 95% confidence interval (CI), 1.39-4.43 for 40-80 µg/day; OR = 2.41, 95% CI, 1.32-4.40 for 80-130 µg/day; and OR = 2.38, 95% CI, 1.26-4.50 for >200 µg/day compared with <40 µg/day], and the main elevation in risk appeared among microcarcinomas (≤1 cm). A decreased risk of papillary macrocarcinomas (>1 cm; OR = 0.26, 95% CI, 0.08-0.85 for 1,860-3,110 µg/day compared with <760 µg/day) was associated with moderate genistein intake among women. CONCLUSIONS: Our study suggests that high coumestrol intake increases the risk of thyroid cancer, especially microcarcinomas, whereas moderate amounts of genistein intake appear to be protective for females with thyroid macrocarcinomas. IMPACT: The study highlights the importance of distinguishing between microcarcinomas and macrocarcinomas in future research on the etiology of thyroid cancer.

14.
Public Health Nutr ; : 1-9, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31787119

RESUMO

OBJECTIVE: To investigate the hypothesis that folic acid supplementation and dietary folate intake before conception and during pregnancy reduce the risk of small for gestational age (SGA) and to examine the joint effect of folic acid supplementation and dietary folate intake on the risk of SGA. DESIGN: Participants were interviewed by trained study interviewers using a standardized and structured questionnaire. Information on birth outcomes and maternal complications was abstracted from medical records and dietary information was collected via a semi-quantitative FFQ before conception and during pregnancy. SETTING: A birth cohort data analysis using the 2010-2012 Gansu Provincial Maternity and Child Care Hospital. PARTICIPANTS: Women (n 8758) and their children enrolled in the study. RESULTS: Folic acid supplementation was associated with a reduced risk of SGA (OR = 0·72, 95 % CI 0·60, 0·86), with the reduced risk seen mainly for SGA at ≥37 weeks of gestational age (OR = 0·70, 95 % CI 0·58, 0·85) and nulliparous SGA (OR = 0·67, 95 % CI 0·54, 0·84). There was no significant association between dietary folate intake and SGA risk. CONCLUSIONS: Our study suggested that folic acid supplementation was associated with a reduced risk of SGA and the risk varied by preterm status and parity.

15.
J Vasc Surg ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31843298

RESUMO

OBJECTIVE: Postcontrast acute kidney injury (PC-AKI) is a dreaded complication of peripheral vascular interventions (PVIs) that depends on the volume of contrast administered as well as a patient's baseline kidney function. However, there is currently no guidance on the volume of contrast that is considered safe especially for patients with advanced chronic kidney disease (CKD). This study aims to characterize the incidence, risk factors for, and outcomes after PC-AKI and define thresholds of safety for contrast volume. METHODS: The Vascular Quality Initiative files for PVI (2010-2018) were reviewed. Patients on dialysis, with renal transplants, or who developed a bleeding complication were excluded. Only records with complete data on baseline creatinine, contrast volume, and PC-AKI (creatinine increase of ≥0.5 mg/dL, or new dialysis requirement) were included. The cumulative incidence of PC-AKI with contrast volume at each stage of CKD was derived. A safe threshold for contrast volume was defined as the volume at which the cumulative incidence of PC-AKI is 0.5% or less. Multivariable logistic regression was used to define risk factors for PC-AKI, and survival analysis was performed using Kaplan-Meier and multivariable Cox proportional hazards regression. RESULTS: A total of 53,780 procedures were included. There were 16,062 patients (29%) with normal kidney function or CKD1, 21,769 (39%) with CKD2, 14,234 (25%) with CKD3, 1471 (3%) with CKD4, and 199 (<1%) with CKD5. The incidence of PC-AKI was 0.9% and increased with each stage of CKD (CKD1, 0.39%; CKD2, 0.45%; CKD3, 1.5%; CKD4, 4.3%; and CKD5, 7.5%). The safe thresholds for contrast volume for advanced CKD were 50, 20, and 9 mL for CKD3, CKD4, and CKD5, respectively. Regression analysis demonstrated that white race (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.54-0.82) and elective surgery (OR, 0.77; 95% CI, 0.62-0.95) were associated with decreased risk of PC-AKI, whereas inpatient status (OR, 14.5; 95% CI, 9.97-21.2), diabetes (OR, 1.27; 95% CI, 1.02-1.58), advanced CKD (CKD3: OR, 3.65; 95% CI, 2.68-4.98; CKD4: OR, 6.98; 95% CI, 4.72-10.3; CKD5: OR, 8.94; 95% CI, 4.53-17.6), critical limb ischemia (OR, 1.51; 95% CI, 1.14-2.00), acute limb ischemia (OR, 2.47; 95% CI, 1.70-3.59), and contrast-to-eGFR ratio (CGR) (2 ≤ CGR < 3: OR, 1.33; 95% CI, 1.02-1.74; 3 ≤ CGR < 4: OR, 1.90; 95% CI, 1.32-2.75; CGR ≥ 4: OR, 1.79; 95% CI, 1.18-2.70) were significantly associated with increased risk for PC-AKI. Patients who developed PC-AKI had worse in-hospital (16.1% vs 0.45%; P < .01) mortality and long-term survival (log-rank P < .01) compared with those without PC-AKI. CONCLUSIONS: PVI are associated with low risk of PC-AKI that significantly increases when patients with advanced CKD undergo high acuity cases. Given the strong association with short-term and long-term mortality, risk of PC-AKI should be minimized by using safe thresholds of contrast volume.

16.
Med Sci Monit ; 25: 9893-9901, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31869828

RESUMO

BACKGROUND The flavones are considered as competent antidiabetic molecules due to their strong antioxidant activities and higher in vivo stability. The present study evaluated the antidiabetic and hypolipidemic effects of 5,7-dimethoxyflavone in streptozotocin (STZ)-induced diabetic rat models. MATERIAL AND METHODS The antidiabetic potential of 5,7-dimethoxyflavone was evaluated in streptozotocin-induced diabetic rats. The serum levels of triglyceride, total cholesterol, and high-density lipoprotein cholesterol were measured using the Randox assay kit. Histopathological examination was carried out by hematoxylin and eosin (HE) staining. RESULTS Oral administration of 5,7-dimethoxyflavone significantly reduced STZ-induced enhancement in blood sugar and glycosylated hemoglobin, as well as significant increases in C-peptide, insulin, hemoglobin, and total protein content (p<0.05). Additionally, treatment with 5,7-dimethoxyflavone resulted in a remarkable increase in non-enzymic antioxidants. Administration of 5,7-dimethoxyflavone had a hypolipidemic effect by significantly reducing levels of serum triglycerides, total cholesterol, and low-density lipoproteins. The histopathological examination of rat pancreases revealed the beneficial effect of 5,7-dimethoxyflavone and protection of ß cell integrity in STZ-induced diabetic rats. CONCLUSIONS These findings reflect the antidiabetic and hypolipidemic effects of 5,7-dimethoxyflavone, suggesting that 5,7-dimethoxyflavone may be a promising compound for use in development of new antidiabetic drugs.

17.
Ann Surg Oncol ; 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31863415

RESUMO

BACKGROUND: The tumor-node-metastasis classification system has proposed that lung cancers presenting as multifocal ground-glass nodules (multi-GGN) on computed tomography scan should be staged as multiple primaries instead of intrapulmonary metastases. However, the problem still exists for those synchronous multiple lung adenocarcinomas (SMLA) involving solid lesions. This study aimed to explore the distinct features of SMLA to better define the diagnosis and staging of this disease. METHODS: Between 2008 and 2016, consecutive patients with complete resection of SMLA were prospectively enrolled in the study. The patients were divided into three groups based on CT images as follows: multi-GGN, one solid nodule plus one or more GGNs (solid-GGN), and multiple solid lesions with or without GGN (multi-solid). Clinicopathologic features and survival outcomes were compared between these groups. Multivariate Cox proportional hazards analyses using bootstrap internal validation were performed to identify independent predictors for recurrence-free survival (RFS) and overall survival (OS). RESULTS: Of the 695 patients who met the inclusion criteria, 486 (69.9%) presented with multi-GGN tumor, 124 (17.9%) with solid-GGN tumor, and 85 (12.2%) with multi-solid tumor. The three groups had distinguished clinicopathologic features of gender, smoking history, nodal metastases, tumor size, subtype, and location (all P < 0.001). Multivariate analyses demonstrated that multi-solid tumor was an independent predictor for both decreased RFS [hazard ratio (HR) 2.941; 95% confidence interval (CI) 1.07-8.08; P = 0.036] and poor OS (HR 6.13; 95% CI 1.15-32.63; P = 0.034), but neither RFS (P = 0.384) nor OS (P = 0.811) differed between solid-GGN and multi-GGN tumors. CONCLUSIONS: Both multi-GGN and solid-GGN tumors should be staged as multiple primaries, whereas multi-solid tumor was indicated to be advanced disease.

18.
Indoor Air ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31755597

RESUMO

Stunting adversely affects physical and mental outcomes of children. It has not been examined whether household air pollution from solid fuel combustion is a risk factor for stunting in children. In a total of 41,439 children aged 6-17 across China, height was measured using a unified protocol. Multivariable linear regression models and logistic regression models were used to assess the associations of solid fuel use for cooking/heating with stunting in children. Adjusted for covariates, cooking/heating with solid fuel was significantly associated with a lower z-score for height for age and sex (ß = -0.21 [-0.32 to -0.09] and -0.17 [-0.31 to -0.03], respectively) and an increased risk of stunting with an estimated ORs of 1.34 [1.07~1.68] and 1.37 [1.02~1.83], respectively. The risk of stunting associated with solid fuel use was statistically significant in high-age children. And the effect was greater on girls than on boys, though the difference was not statistically significant. Our study suggested that Chinese children living in households using solid fuel had a significantly higher risk of stunting than those living in households using cleaner fuel.

19.
Ann Vasc Surg ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31756416

RESUMO

BACKGROUND: Critical limb ischemia (CLI) is the clinical manifestation of severe peripheral artery disease presenting as rest pain (RP) and tissue loss (TL). Most studies compare CLI as a homogenous group with claudication with limited database studies specifically studying these differences. We hypothesize that CLI should be stratified into RP and TL because of significant differences in disease severity, comorbidities, and outcomes. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2016 was reviewed. All patients with a postoperative diagnosis of CLI undergoing femoral to popliteal bypass (FPB) with vein or graft were identified. Patients were stratified into cohorts based on International Classification of Disease (ICD)-9 or ICD-10 codes for RP or TL (gangrene or ulcer). Univariate and multivariate analyses were performed to examine 30-day mortality, morbidity, major amputation, and readmission adjusting for demographics, comorbidities, and procedural details. RESULTS: There were 5,304 patients. Compared to RP, patients with TL were older (P < 0.0001) and more likely to be dependent (P < 0.0001). TL patients were also more likely to have diabetes (P < 0.0001), congestive heart failure (P < 0.0001), renal failure (P = 0.004), dialysis (P < 0.0001), history of wound infection (P < 0.0001), and sepsis (P < 0.0001). TL patients had higher American Society of Anesthesiologists class (P < 0.0001), were less likely to be transferred from home (P < 0.0001), and more likely to receive an FPB with vein (P = 0.03). Patients with TL had worse perioperative outcomes compared with RP in terms of pneumonia (P = 0.004), unplanned intubation (P = 0.009), cardiac arrest requiring cardiopulmonary resuscitation (P = 0.003), bleeding requiring transfusions (P < 0.0001), sepsis (P < 0.0001), septic shock (P = 0.02), and reoperation (P < 0.0001). TL was associated with significantly higher 30-day morbidity (P < 0.0001), 30-day mortality (P < 0.0001), major amputation (P = 0.0004), and readmission rates (P = 0.005). Patients with TL compared with those with RP also had longer hospital stays (P < 0.0001) and days between operation to discharge (P < 0.0001). TL was independently associated with increased 30-day morbidity (OR: 1.16 [1.00-1.35]) and major amputation (OR: 2.48 [1.29-4.76]) compared with RP. CONCLUSIONS: Patients with RP and TL have drastic differences that impact perioperative mortality and readmissions. TL is an independent predictor of 30-day morbidity and major amputation. The stratification of CLI into RP and TL can provide insight into variations in outcomes and provide a means to quantify the risks associated with the 2 manifestations of the disease.

20.
Am J Epidemiol ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31742588

RESUMO

A nested case-control study was carried out using data from the United States Department of Defense cohort between 2000 and 2013 to investigate the associations of papillary thyroid cancer (PTC) with serum concentrations of polybrominated diphenyl ethers and polybrominated biphenyls. This study included 742 (341 women and 401 men) histologically confirmed PTC cases and 742 matched controls with pre-diagnostic serum samples from the Department of Defense Serum Repository. Lipid-corrected serum concentrations of eight congeners were measured. Multivariate conditional logistic regression analyses were performed for classical PTC and follicular variant of PTC, respectively. We also examined effect modification by gender. BDE-28 was associated with significantly increased risk of classical PTC [OR=2.09; 95% CI, 1.05, 4.15, for the 3rd tertile vs. below limit of detection; Ptrend=0.02], adjusting for other congeners, body mass index, and branch of military service. This association was mainly observed for larger classical PTC (tumor size >10 mm) with a significantly stronger association among women than men (Pinteraction=0.004). No consistent associations were observed for other congeners, including those at higher concentrations. This study found a significantly increased risk of classical PTC associated with increasing levels of BDE-28. The risk varied by gender and tumor size.

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