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BACKGROUND: The phase III MONALEESA trials tested the efficacy and safety of the cyclin-dependent kinase (CDK)4/6 inhibitor ribociclib with different endocrine therapy partners as first- or second-line treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer (ABC). Using the largest pooled biomarker dataset of the CDK4/6 inhibitor ribociclib in ABC to date, we identified potential biomarkers of response to ribociclib. PATIENTS AND METHODS: Baseline circulating tumour DNA from patients in the MONALEESA trials was assessed using next-generation sequencing. An analysis of correlation between gene alteration status and progression-free survival (PFS) was carried out to identify potential biomarkers of response to ribociclib. RESULTS: Multiple frequently altered genes were identified. Alterations in ERBB2, FAT3, FRS2, MDM2, SFRP1, and ZNF217 were associated with a greater PFS benefit with ribociclib versus placebo. Patients with high tumour mutational burden (TMB) and with ANO1, CDKN2A/2B/2C, and RB1 alterations exhibited decreased sensitivity to ribociclib versus placebo. CONCLUSIONS: Although exploratory, these results provide insight into alterations associated with the improved response to ribociclib treatment and may inform treatment sequencing in patients with actionable alterations following progression on CDK4/6 inhibitors. Validation of potential biomarkers identified here and development of prospective trials testing their clinical utility are warranted. GOV IDENTIFIERS: NCT01958021, NCT02422615, NCT02278120.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Letrozole , Prospective Studies , Aminopyridines/therapeutic use , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
Objective: To develop asolvent extraction-direct mercury analyzer method for determination of methylmercury in urine. Methods: After the urinehydrolyzesd by hydrobromic acid, methylmercury was extracted by tolueneand reverse-extracted from L-cysteine solution, it was then detectedbydirect mercuryanalyzer. Results: The linear range was 0.2-50.0 µg/L, and the related coefficient was 0.9999. The relative standard deviations (RSD) within the group were 5.04%-6.64%, and the RSD between the group were 5.65%-8.11 %. The average recovery efficiencies were 85.4%-95.5%. The detection limitation was 0.0482 µg/L and the quantification concentrations was 0.1607 µg/L. Conclusion: The method, which has low detection limit, high sensitivity, easy to operate, is stability for the determination of methylmercury in urine.
Subject(s)
Mercury , Methylmercury CompoundsABSTRACT
BACKGROUND: Voriconazole is a new generation of broad-spectrum antifungal agents commonly used in the treatment of invasive aspergillus infections. CASE REPORT: We reported a rare case of myopathy induced by voriconazole, which showed severe muscle pain and significantly elevated myocardial enzymes. Enzymes eventually achieved good efficacy by switching voriconazole to micafungin and the use of L-carnitine. CONCLUSIONS: This reminded us it was necessary to be vigilant for rare adverse reactions of voriconazole in the population with liver dysfunction, the elderly population, and people with multiple underlying diseases in clinical practice. During medication of voriconazole, close attention should be paid to the occurrence of adverse reactions to avoid life-threatening complications.
Subject(s)
Liver Cirrhosis, Alcoholic , Triazoles , Aged , Humans , Voriconazole/adverse effects , Liver Cirrhosis, Alcoholic/drug therapy , Triazoles/pharmacology , Antifungal Agents/therapeutic use , MicafunginABSTRACT
Lymph node metastasis is related to poor prognosis in oral squamous cell carcinoma (OSCC), and few studies have explored the relevance of postoperative drainage fluid (PDF) in metastasis. Extracellular vesicles (EVs) are nanosized vesicles that can transfer oncogenic molecules to regulate tumorigenesis. However, the proteomic profile of postoperative drainage fluid-derived EVs (PDF-EVs) in OSCC has not been elucidated. Herein, we collected drainage fluid from OSCC patients after neck dissection to investigate the difference in PDF-EVs between patients with metastatic lymph nodes (the LN+ group) and nonmetastatic lymph nodes (the LN- group). The proteomic profile of PDF-EVs from the LN+ and LN- groups was compared using label-free liquid chromatography tandem-mass spectrometry-based protein quantification. The results revealed that PDF-EVs were mainly derived from epithelial cells and immune cells. A total of 2,134 proteins in the PDF-EVs were identified, and 313 were differentially expressed between the LN+ and LN- groups. Metabolic proteins, such as EHD2 and CAVIN1, were expressed at higher levels in the LN+ group than in the LN- group, and the levels of EHD2 and CAVIN1 in the postoperative drainage fluid were positively correlated with lymph node metastasis. Our study revealed previously undocumented postoperative drainage fluid-associated proteins in patients with metastatic OSCC, providing a starting point for understanding their role in metastatic and nonmetastatic OSCC.
Subject(s)
Carcinoma, Squamous Cell , Extracellular Vesicles , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Carcinoma, Squamous Cell/metabolism , Squamous Cell Carcinoma of Head and Neck/pathology , Mouth Neoplasms/metabolism , Neck Dissection , Lymphatic Metastasis , Proteomics/methods , Biomarkers, Tumor/metabolism , Lymph Nodes , Proteins , Extracellular Vesicles/metabolism , Head and Neck Neoplasms/metabolismABSTRACT
Operator spreading, often characterized by out-of-time-order correlators (OTOCs), is one of the central concepts in quantum many-body physics. However, measuring OTOCs is experimentally challenging due to the requirement of reversing the time evolution of systems. Here we apply Floquet engineering to investigate operator spreading in a superconducting 10-qubit chain. Floquet engineering provides an effective way to tune the coupling strength between nearby qubits, which is used to demonstrate quantum walks with tunable couplings, reversed time evolution, and the measurement of OTOCs. A clear light-cone-like operator propagation is observed in the system with multiple excitations, and has a nearly equal velocity as the single-particle quantum walk. For the butterfly operator that is nonlocal (local) under the Jordan-Wigner transformation, the OTOCs show distinct behaviors with (without) a signature of information scrambling in the near integrable system.
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Objective: To construct the diagnostic model of superficial esophageal squamous cell carcinoma (ESCC) and precancerous lesions in endoscopic images based on the YOLOv5l model by using deep learning method of artificial intelligence to improve the diagnosis of early ESCC and precancerous lesions under endoscopy. Methods: 13, 009 endoscopic esophageal images of white light imaging (WLI), narrow band imaging (NBI) and lugol chromoendoscopy (LCE) were collected from June 2019 to July 2021 from 1, 126 patients at the Cancer Hospital, Chinese Academy of Medical Sciences, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, ESCC limited to the mucosal layer, benign esophageal lesions and normal esophagus. By computerized random function method, the images were divided into a training set (11, 547 images from 1, 025 patients) and a validation set (1, 462 images from 101 patients). The YOLOv5l model was trained and constructed with the training set, and the model was validated with the validation set, while the validation set was diagnosed by two senior and two junior endoscopists, respectively, to compare the diagnostic results of YOLOv5l model and those of the endoscopists. Results: In the validation set, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the YOLOv5l model in diagnosing early ESCC and precancerous lesions in the WLI, NBI and LCE modes were 96.9%, 87.9%, 98.3%, 88.8%, 98.1%, and 98.6%, 89.3%, 99.5%, 94.4%, 98.2%, and 93.0%, 77.5%, 98.0%, 92.6%, 93.1%, respectively. The accuracy in the NBI model was higher than that in the WLI model (P<0.05) and lower than that in the LCE model (P<0.05). The diagnostic accuracies of YOLOv5l model in the WLI, NBI and LCE modes for the early ESCC and precancerous lesions were similar to those of the 2 senior endoscopists (96.9%, 98.8%, 94.3%, and 97.5%, 99.6%, 91.9%, respectively; P>0.05), but significantly higher than those of the 2 junior endoscopists (84.7%, 92.9%, 81.6% and 88.3%, 91.9%, 81.2%, respectively; P<0.05). Conclusion: The constructed YOLOv5l model has high accuracy in diagnosing early ESCC and precancerous lesions in endoscopic WLI, NBI and LCE modes, which can assist junior endoscopists to improve diagnosis and reduce missed diagnoses.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Precancerous Conditions , Artificial Intelligence , Endoscopy/methods , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/diagnostic imaging , Humans , Narrow Band Imaging , Precancerous Conditions/diagnostic imaging , Sensitivity and SpecificityABSTRACT
A 70-year-old male patient, who had a right upper eyelid tumor excision 4 years ago, complained of eyelid swelling and ptosis for 3 months. Orbital CT and MRI showed an orbital cystic lesion with hemorrhage in the right eye. The tumor was resected under general anesthesia. The pathological diagnosis was epithelioid hemangioendothelioma. (Chin J Ophthalmol, 2021, 57:696-698).
Subject(s)
Blepharoptosis , Hemangioendothelioma, Epithelioid , Adult , Aged , Child , Eyelids , Hemangioendothelioma, Epithelioid/diagnostic imaging , Hemangioendothelioma, Epithelioid/surgery , Humans , Magnetic Resonance Imaging , MaleABSTRACT
AIMS: Various applications of microbially induced carbonate precipitation (MICP) has been proposed. However, most studies use cultured pure strains to obtain MICP, ignoring advantages of microbial consortia. The aims of this study were to: (i) test the feasibility of a microbial consortium to produce MICP; (ii) identify functional micro-organisms and their relationship; (iii) explain the MICP mechanism; (iv) propose a way of applying the MICP technique to soil media. METHODS AND RESULTS: Anaerobic sludge was used as the source of the microbial consortium. A laboratory anaerobic sequencing batch reactor and beaker were used to perform precipitation experiment. The microbial consortium produced MICP with an efficiency of 96·6%. XRD and SEM analysis showed that the precipitation composed of different-size calcite crystals. According to high-throughput 16S rRNA gene sequencing, the functional micro-organisms included acetogenic bacteria, acetate-oxidizing bacteria and archaea Methanosaeta and Methanobacterium beijingense. The methanogenesis acetate degradation provides dissolved inorganic carbon and increases pH for MICP. A series of reactions catalysed by many enzymes and cofactors of methanogens and acetate-oxidizers are involved in the acetate degradation. CONCLUSION: This work demonstrates the feasibility of using the microbial consortium to achieve MICP from an experimental and theoretical perspective. SIGNIFICANCE AND IMPACT OF THE STUDY: A method of applying the microbial-consortium MICP to soil media is proposed. It has the advantages of low cost, low environmental impact, treatment uniformity and less limitations from natural soils. This method could be used to improve mechanical properties, plug pores and fix harmful elements of soil media, etc.
Subject(s)
Archaea/physiology , Bacteria, Anaerobic/physiology , Calcium Carbonate/metabolism , Carbonates/metabolism , Microbial Consortia , Acetates/metabolism , Anaerobiosis , Carbon Compounds, Inorganic/metabolism , Chemical Precipitation , DNA, Bacterial/genetics , High-Throughput Nucleotide Sequencing , Hydrogen-Ion Concentration , Industrial Microbiology/methods , Metabolic Networks and Pathways , Methane/metabolism , Microbial Interactions , RNA, Ribosomal, 16S/genetics , Sewage/microbiology , Soil MicrobiologyABSTRACT
OBJECTIVE: To investigate the value of narrow-band imaging training for differentiating between benign and malignant vocal fold leukoplakia. METHOD: Thirty cases of vocal fold leukoplakia were selected. RESULTS: Narrow-band imaging endoscopy training had a significant positive effect on the specificity of the differential diagnosis of vocal fold leukoplakia. In addition, the consistency of diagnostic typing of vocal fold leukoplakia by narrow-band imaging improved to 'moderate agreement' following the combination of types I and II and the combination of types IV, V and VI in the typing of vocal fold leukoplakia. CONCLUSION: The narrow-band imaging training course may improve the ability of laryngologists to diagnose vocal fold leukoplakia. The new endoscopic diagnostic classification by narrow-band imaging needs to be further simplified to facilitate clinical application.
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Objective: To explore the association between parental socioeconomic status (SES) and preschoolers' consumption of sugar-sweetened beverages (SSB). Methods: In June 2018, all preschoolers from 15 kindergartens were selected from the jurisdiction of Education Commission in Dongcheng District of Beijing by using an equal-proportion stratified cluster sampling method in the study. A self-designed questionnaire was used to investigate the parents of preschoolers to obtain the basic information of preschoolers and parents, the consumption situation of preschoolers' sugar-sweetened beverages and the perception of parents to SSB. A tatol of 3 217 preschoolers were finally included in the analysis. A generalized structural equation model was used to analyze the relationship between preschoolers' consumption of sugar-sweetened beverages and their parents' socioeconomic status and the mediating effect of their cognition of sugar-sweetened beverages. The size of mediating effect was estimated by using deviation correction non-parameter percentile Bootstrap method. Results: The age of 3 217 preschoolers was (4.23±0.67) years, of which 52.6% (n=1 692) were boys, and 77.62% (n=2 497) were SSB consumers. Among the parents of 3 217 preschoolers, fathers and mothers accounted for 24.90% (n=801) and 75.10% (n=2 416), and the M (P25, P75) scores of SES were 66.7 (62.5, 69.5) and 69.5 (64.6, 71.4), respectively. The proportion of parents who took the initiative to learn about their children's consumption of SSB, lacked confidence in restricting preschooler's consumption of SSB and read nutrition labels before purchasing food was 74.08% (n=2 383), 82.90% (n=2 667) and 36.24% (n=1 166), respectively. The generalized structural equation model showed that after adjusting for preschoolers' gender, age, body mass index (BMI) of preschoolers and their parents, preschoolers' consumption of SSB was negatively associated with their parents' SES score [path coefficient (95%CI):-4.69×10-2 (-6.56×10-2,-2.69×10-2) ]. The mediating effect of parents' perception of SSB consumption could explain 48.71% of the total effect [path coefficient (95%CI):-2.28×10-2 (-3.54×10-2, -1.10×10-2)]. Conclusion: The consumption of SSB in preschoolers is negatively associated with their parent's SES, and this relationship is partially mediated by parent's perception of SSB consumption.
Subject(s)
Beverages , Sugar-Sweetened Beverages , Beijing , Child , Female , Humans , Male , Schools , Social ClassABSTRACT
OBJECTIVE: The aim of this study was to investigate the potential role of LINC00511 in esophageal cancer (ECa), and to explore its underlying mechanism through in vitro cell experiments. PATIENTS AND METHODS: LINC00511 expression in ECa was analyzed by GEPIA database and verified by real-time fluorescence quantitative polymerase chain reaction (qPCR). The bioinformatics website was used to analyze the miRNAs that can bind to LINC00511, and the regulatory relationship between them was verified through Luciferase assay, qPCR as well as Western blotting analysis. Then, the impacts of LINC00511 and microRNA-150-5p on the proliferation or invasiveness of ECa cell lines Kyse30 and ECA109 were investigated by cell counting kit-8 (CCK-8) test and transwell experiment, respectively. Meanwhile, cell cycle and apoptosis were detected by flow cytometry. RESULTS: Analysis results of the GEPIA database revealed that LINC00511 had a significant high expression in ECa tissue samples in comparison with normal control ones, which is consistent with qPCR results. Meanwhile, a significant negative correlation was found between LINC00511 and microRNA-150-5p. In brief, LINC00511 was able to bind to microRNA-150-5p and inhibited its expression. Besides, overexpression of LINC00511 enhanced ECa cell proliferation and migration, accelerated cell cycle, and suppressed cell apoptosis, while transfection with microRNA-150-5p mimics caused the opposite effects. CONCLUSIONS: This study shows for the first time that LINC00511 modulates the progression of ECa by binding to microRNA-150-5p.
Subject(s)
Esophageal Neoplasms/metabolism , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , Cell Movement , Cell Proliferation , Cells, Cultured , Esophageal Neoplasms/pathology , Humans , MicroRNAs/genetics , RNA, Long Noncoding/geneticsABSTRACT
There is a paucity of data on additive manufacturing process emissions and personal exposures in real-world workplaces. Hence, we evaluated atmospheres in four workplaces utilizing desktop "3-dimensional" (3-d) printers [fused filament fabrication (FFF) and sheer] for production, prototyping, or research. Airborne particle diameter and number concentration and total volatile organic compound concentrations were measured using real-time instruments. Airborne particles and volatile organic compounds were collected using time-integrated sampling techniques for off-line analysis. Personal exposures for metals and volatile organic compounds were measured in the breathing zone of operators. All 3-d printers that were monitored released ultrafine and fine particles and organic vapors into workplace air. Particle number-based emission rates (#/min) ranged from 9.4 × 109 to 4.4 × 1011 (n = 9samples) for FFF3-d printers and from 1.9 to 3.8 × 109 (n = 2 samples) for a sheer 3-d printer. The large variability in emission rate values reflected variability from the printers as well as differences in printer design, operating conditions, and feedstock materials among printers. A custom-built ventilated enclosure evaluated at one facility was capable of reducing particle number and total organic chemical concentrations by 99.7% and 53.2%, respectively. Carbonyl compounds were detected in room air; however, none were specifically attributed to the 3-d printing process. Personal exposure to metals (aluminum, iron) and 12 different organic chemicals were all below applicable NIOSH Recommended Exposure Limit values, but results are not reflective of all possible exposure scenarios. More research is needed to understand 3-d printer emissions, exposures, and efficacy of engineering controls in occupational settings.
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Little is known about emissions and exposure potential from vat polymerization additive manufacturing, a process that uses light-activated polymerization of a resin to build an object. Five vat polymerization printers (three stereolithography (SLA) and two digital light processing (DLP) were evaluated individually in a 12.85 m3 chamber. Aerosols (number, size) and total volatile organic compounds (TVOC) were measured using real-time monitors. Carbonyl vapors and particulate matter were collected for offline analysis using impingers and filters, respectively. During printing, particle emission yields (#/g printed) ranged from 1.3 ± 0.3 to 2.8 ± 2.6 x 108 (SLA printers) and from 3.3 ± 1.5 to 9.2 ± 3.0 x 108 (DLP printers). Yields for number of particles with sizes 5.6 to 560 nm (#/g printed) were 0.8 ± 0.1 to 2.1 ± 0.9 x 1010 and from 1.1 ± 0.3 to 4.0 ± 1.2 x 1010 for SLA and DLP printers, respectively. TVOC yield values (µg/g printed) ranged from 161 ± 47 to 322 ± 229 (SLA printers) and from 1281 ± 313 to 1931 ± 234 (DLP printers). Geometric mean mobility particle sizes were 41.1-45.1 nm for SLA printers and 15.3-28.8 nm for DLP printers. Mean particle and TVOC yields were statistically significantly higher and mean particle sizes were significantly smaller for DLP printers compared with SLA printers (p < 0.05). Energy dispersive X-ray analysis of individual particles qualitatively identified potential occupational carcinogens (chromium, nickel) as well as reactive metals implicated in generation of reactive oxygen species (iron, zinc). Lung deposition modeling indicates that about 15-37% of emitted particles would deposit in the pulmonary region (alveoli). Benzaldehyde (1.0-2.3 ppb) and acetone (0.7-18.0 ppb) were quantified in emissions from four of the printers and 4-oxopentanal (0.07 ppb) was detectable in the emissions from one printer. Vat polymerization printers emitted nanoscale particles that contained potential carcinogens, sensitizers, and reactive metals as well as carbonyl compound vapors. Differences in emissions between SLA and DLP printers indicate that the underlying technology is an important factor when considering exposure reduction strategies such as engineering controls.
Subject(s)
Air Pollution, Indoor/analysis , Particulate Matter/analysis , Printing, Three-Dimensional , Volatile Organic Compounds/analysis , Carcinogens , Metals , Particle Size , Particulate Matter/chemistry , PolymerizationABSTRACT
Objective: To explore the association of platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) with protein energy wasting (PEW) in maintenance hemodialysis (MHD) patients. Methods: A multicenter cross-sectional study was conducted in eleven hemodialysis centers of Guizhou province from June to August, 2017. Clinical data, physical parameters, body composition data and laboratory values of MHD patients were collected. PLR and NLR were calculated according to routine blood test. All patients were divided into four groups (Q1-Q4) according to the median and quartile of PLR and NLR. Multivariate logistic regression models were applied to analyze the relationships between PLR, NLR and PEW. The comparison of predictive power of PLR and NLR for PEW was evaluated by receiver operating characteristic curve (ROC). Results: A total of 936 MHD patients were enrolled (519 males, 417 females), with a mean age of (55.6±15.6) years. The prevalence of PEW was 46.2% (432/936). Multivariate logistic regression analysis showed that patients in group PLR Q3 and Q4 were 2.07 (95%CI: 1.03-4.13, P=0.014) and 2.73 (95%CI: 1.58-4.74, P<0.001) times more likely to have PEW, compared with those in group PLR Q1 in unadjusted models. PLR was significantly associated with the development of PEW after adjusting age, sex, history of hypertension, diabetes and hemoglobin. Patients in Group PLR Q3 and Q4 were 2.82 times (95%CI: 1.42-5.60, P=0.003) and 2.93 times (95%CI: 1.50-5.73, P=0.002) times more likely to have PEW than those in Group PLR Q1. The ROC showed that only PLR can predict the development of PEW with a diagnostic threshold of 144.09 [area under curve (AUC)=0.61, 95%CI: 0.56-0.66, P<0.001], with a sensitivity and specificity of 61% and 58%, respectively, while the AUC of NLR is 0.55 (P=0.091). Conclusion: For MHD patients, only PLR could be a relevent factor of PEW and it showed the predictive power of PEW rather than NLR.
Subject(s)
Lymphocytes , Neutrophils , Renal Dialysis , Adult , Aged , Blood Platelets , Cross-Sectional Studies , Female , Humans , Leukocyte Count , Male , Middle Aged , Prognosis , Retrospective StudiesABSTRACT
OBJECTIVES: The prognostic value of quantitative diffusion-weighted magnetic resonance imaging (DWI MRI) in predicting neurologic outcomes after pediatric cardiopulmonary arrest (CPA) has not been determined. The aim of this study was to identify a DWI MRI threshold for brain volume percent that correlates with neurologic outcome in children who remain comatose or display significant neurologic deficits immediately after resuscitation from CPA. METHODS: This single-center retrospective study analyzed DWI MRIs of pediatric patients who remained neurologically impaired after CPA. Any MRI obtained within 2 weeks after CPA was analyzed. The apparent diffusion coefficient (ADC) value of each voxel within the brain was determined. Percentage brain volume with voxels below each ADC threshold between 300 and 1200â¯×â¯10-6â¯mm2/s with a step of 50 were calculated. Area under the receiver operating characteristics curve (AUC) was used to identify optimal DWI MRI thresholds for brain volume percent most predictive of poor neurologic outcome. The primary outcome measure was neurologic outcome 6-months after CPA based on Pediatric Cerebral Performance Category (PCPC) score. Poor neurologic outcome was defined as PCPC score of 3-6, or a worsening from baseline score ≥1 if baseline PCPC score was ≥3. RESULTS: Twenty-six patients were included in this study. The median age was 8.5 years (2.2-14) and median time from CPA to MRI was 4â¯days (2-7). Two ADC thresholds for brain volume percent had the largest AUC for predicting poor neurologic outcome. An ADC threshold of <600â¯×â¯10-6â¯mm2/s in ≥7% of brain volume; and <650â¯×â¯10-6â¯mm2/s in ≥11% of brain volume both demonstrated a specificity of 1.0 (0.76-1.0, 95% CI) and a sensitivity of 0.8 (0.44-0.96, 95% CI) for poor outcome. CONCLUSIONS: In pediatric patients who remain comatose or have significant neurologic deficits after CPA, quantitative DWI MRI correlates with neurologic outcome. Both an ADC threshold of <600â¯×â¯10-6â¯mm2/s in ≥7% of brain volume and <650â¯×â¯10-6 mm2/s in ≥11% of brain volume are highly specific for predicting poor neurologic outcome. A prospective trial to validate these thresholds is needed.
Subject(s)
Coma , Diffusion Magnetic Resonance Imaging/methods , Heart Arrest , Nervous System Diseases , Resuscitation , Brain/diagnostic imaging , Brain/pathology , Child , Coma/diagnosis , Coma/etiology , Correlation of Data , Female , Heart Arrest/complications , Heart Arrest/therapy , Humans , Male , Nervous System Diseases/diagnosis , Nervous System Diseases/etiology , Neurologic Examination , Organ Size , Outcome Assessment, Health Care/methods , Predictive Value of Tests , Prognosis , Resuscitation/adverse effects , Resuscitation/methods , Retrospective Studies , United StatesABSTRACT
AIM: To characterize haemoglobin A1c (HbA1c) trajectories and examine their associations with chronic kidney disease (CKD) progression. METHODS: This was a prospective cohort study on 770 patients with type 2 diabetes mellitus (T2DM) attending a diabetes centre in 2002-2017. Group-based trajectory modelling was used to identify HbA1c trajectories. Cox proportional hazards models were used to examine association between the trajectories and CKD progression which was defined as deterioration across the Kidney Disease: Improving Global Outcomes estimated glomerular filtration rate categories with ≥25% drop from baseline. RESULTS: We identified four HbA1c trajectories: 'near-optimal stable' (49.1%), 'moderate stable' (37.9%), 'moderate-increasing' (6.0%) and 'high-decreasing' (7.0%). Over a median follow-up period of 4.6 years (interquartile range 2.5-5.6), CKD progression occurred in 35.6% of patients. The risk of CKD progression was significantly higher in the moderate-increasing with adjusted hazard ratios (HR) 2.23 (95% confidence interval (CI) 1.09-4.57). After additional adjustment for mean HbA1c, the association between the moderate-increasing subgroup and CKD progression remained significant at HR 3.07 (95% CI 1.08-8.77). CONCLUSION: Moderate-increasing HbA1c trajectory is associated with renal disease progression in patients with T2DM, independent of mean HbA1c. The deleterious effects of deteriorating HbA1c trajectory highlight the importance of achieving sustained good glycaemic control in diabetes management.
Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Glycated Hemoglobin/analysis , Renal Insufficiency, Chronic/blood , Cohort Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetic Nephropathies/blood , Diabetic Nephropathies/diagnosis , Diabetic Nephropathies/epidemiology , Diabetic Nephropathies/etiology , Disease Progression , Female , Humans , Kidney Function Tests/methods , Kidney Function Tests/statistics & numerical data , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/etiology , Risk Factors , Singapore/epidemiologyABSTRACT
Objective: To examine the relationship between low serum parathyroid hormone (PTH) and protein-energy wasting (PEW) in patients who underwent maintenance hemodialysis (MHD) treatment. Methods: A cross-sectional study was conducted in MHD patients between June 2015 and August 2017 in 11 MHD centers from Guizhou province. Body composition and physical parameters were measured, clinical data and other related laboratory values were collected according to the medical record system. Participants were assigned to low serum PTH group (PTH<150 ng/L), target PTH group (150 ng/L≤ PTH ≤300 ng/L) and high serum PTH group (PTH>300 ng/L). Multivariate logistic regression analysis was used to analyze the relationship between low serum PTH and risk of PEW, which was diagnosed according to the diagnostic criteria recommened by the International Society of Renal Nutrition and Metabolism (ISRNM). Results: A total of 873 MHD patients (488 males and 385 females) were included in the final analysis, with a mean age of 55.0 (44.0, 67.0) years and a mean hemodialysis duration of 31.0(17.0, 54.0) months. In unadjusted model, low serum PTH group was associated with PEW (OR=2.12, 95% CI: 1.26-3.54, P=0.004), when compared with high serum PTH group. After adjustment for age and sex, low serum PTH group was still significantly associated with PEW (OR=2.09, 95% CI: 1.23-3.52, P=0.006). Further adjustment for diabetes and hypertension, the correlation between low serum PTH group and PEW was still significant (OR=2.02, 95% CI: 1.04-3.90, P=0.037). However, the correlation was not observed in target PTH group and high serum PTH group. Conclusion: Low serum PTH was associated with risk of PEW, regardless of age, sex, history of diabetes and hypertension, and thus it might be a promising indicator of PEW in MHD patients.