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1.
Cell Death Dis ; 12(10): 926, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34628463

RESUMO

Photoreceptor death and neurodegeneration is the leading cause of irreversible vision loss. The inflammatory response of microglia plays an important role in the process of neurodegeneration. In this study, we chose retinal detachment as the model of photoreceptor degeneration. We found Myosin 1f was upregulated after retinal detachment, and it was specifically expressed in microglia. Deficiency of myosin 1f protected against photoreceptor apoptosis by inhibiting microglia activation. The elimination of microglia can abolish the protective effect of myosin 1f deficiency. After stimulation by LPS, microglia with myosin 1f deficiency showed downregulation of the MAPK and AKT pathways. Our results demonstrated that myosin 1f plays a crucial role in microglia-induced neuroinflammation after retinal injury and photoreceptor degeneration by regulating two classic inflammatory pathways and thereby decreasing the expression of inflammatory cytokines. Knockout of myosin 1f reduces the intensity of the immune response and prevents cell death of photoreceptor, suggesting that myosin 1f can be inhibited to prevent a decline in visual acuity after retinal detachment.

2.
Front Endocrinol (Lausanne) ; 12: 711540, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603201

RESUMO

Objective: The aim of the study was to investigate the association between the visit-to-visit variability (VVV) of fasting plasma glucose (FPG) and arterial stiffness in Chinese adults. Methods: We performed a cohort study involving 2002 Chinese adults with no history of myocardial infarction or stroke. All the participants attended three visits (the baseline visit in 2008, the 2nd visit in 2009 and the 3rd visit in 2013). We used four measures to define the VVV of FPG across the three visits: the standard deviation (SD), the coefficient of variation (CV), the average successive variability (ASV) and the variability independent of the mean (VIM). We used brachial-ankle pulse wave velocity (ba-PWV) to measure arterial stiffness at the 2nd and the 3rd visits. Results: Compared with the lowest tertile of all the four measurements of VVV of FPG, significantly increased levels of ba-PWV change, ratio of ba-PWV change and the occurrence of the elevated ba-PWV were found in the highest tertile. The odds ratio (OR) and 95% confidence interval (CI) comparing participants in the highest tertile vs. the lowest tertile of FPG-SD was 1.37 (1.01-1.86) for risks of having elevated ba-PWV, even after adjustment for covariates including the mean FPG. Similar results were found for FPG-CV and FPG-VIM. Conclusion: Greater long-term variability of FPG was associated with an increased risk of arterial stiffness, suggesting that the VVV of FPG could be used for an early detection of subclinical atherosclerosis.

3.
Int J Med Sci ; 18(15): 3498-3505, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522176

RESUMO

Sox transcription factors play many diverse roles during development, including regulating stem cell states, directing differentiation, and influencing the local chromatin landscape. Sox10 has been implicated in the control of stem/progenitor activity and epithelial-mesenchymal transition, yet it has not been studied in relation to the hair follicle cycle or hair follicle stem cell (HFSC) control. To elucidate the role of Sox10 in hair follicle cycle control, we performed immunohistochemical and immunofluorescence analysis of its expression during hair morphogenesis, the postnatal hair cycle, and the depilation-induced murine hair follicle cycle. During hair follicle morphogenesis, Sox10 was expressed in the hair germ and peg. In telogen, we detected nuclear Sox10 in the hair bulge and germ cell cap, where HFSCs reside, while in anagen and catagen, Sox10 was detected in the epithelial portion, such as the strands of keratinocytes, the outer root sheath (ORS) in anagen, and the regressed epithelial strand of hair follicle in catagen. These results suggest that Sox10 may be involved in early hair follicle morphogenesis and postnatal follicular cycling.

4.
Plast Reconstr Surg ; 148(4): 850-860, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34550942

RESUMO

BACKGROUND: In ear reconstruction, the difficulty lies in reestablishing the ear's bionic form with adequate skin coverage and an appropriate framework. Skin expansion and a porous polyethylene (i.e., Medpor) framework are often used for ear reconstruction. However, a long-term review of the combined application of the expanded skin and Medpor framework has not been reported. This article reviews ear reconstruction combining these two factors over the past 20 years in the authors' center to summarize the surgical technique and analyze the postoperative results and complications. METHODS: A retrospective review was performed that included all patients who underwent ear reconstruction with expanded skin and Medpor framework in the authors' center between 1998 and 2018. RESULTS: A total of 68 patients with microtia who were admitted to the authors' center for surgical ear reconstruction were included, and 70 ears were reconstructed. Fifty-seven of the patients (83.82 percent) felt satisfied with their reconstructed ear, five patients (7.35 percent) were not satisfied with the reconstructed ear, and six patients (8.82 percent) had the frameworks removed. Fifteen patients (22.06 percent) developed complications, including framework exposure (13.24 percent), infection (4.41 percent), scar hypertrophy (4.41 percent), and hematoma (2.94 percent). CONCLUSIONS: Framework exposure limits the combined application of expanded skin flap and Medpor framework when reconstructing the ear without additional fascial interposition. Using a temporoparietal fascia or postauricular fascia flap during the operation is effective to decrease the exposure rate; however, this complication cannot be completely avoided. Using postauricular fascia and skin graft may lead to scar hypertrophy; thus, these techniques should be used with caution. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

5.
mBio ; : e0229821, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34579580

RESUMO

Polyketides are one of the largest categories of secondary metabolites, and their biosynthesis is initiated by polyketide synthases (PKSs) using coenzyme A esters of short fatty acids (acyl-CoAs) as starter and extender units. In this study, we discover a universal regulatory mechanism in which the starter and extender units, beyond direct precursors of polyketides, function as ligands to coordinate the biosynthesis of antibiotics in actinomycetes. A novel acyl-CoA responsive TetR-like regulator (AcrT) is identified in an erythromycin-producing strain of Saccharopolyspora erythraea. AcrT shows the highest binding affinity to the promoter of the PKS-encoding gene eryAI in the DNA affinity capture assay (DACA) and directly represses the biosynthesis of erythromycin. Propionyl-CoA (P-CoA) and methylmalonyl-CoA (MM-CoA) as the starter and extender units for erythromycin biosynthesis can serve as the ligands to release AcrT from PeryAI, resulting in an improved erythromycin yield. Intriguingly, anabolic pathways of the two acyl-CoAs are also suppressed by AcrT through inhibition of the transcription of acetyl-CoA (A-CoA) and P-CoA carboxylase genes and stimulation of the transcription of citrate synthase genes, which is beneficial to bacterial growth. As P-CoA and MM-CoA accumulate, they act as ligands in turn to release AcrT from those targets, resulting in a redistribution of more A-CoA to P-CoA and MM-CoA against citrate. Furthermore, based on analyses of AcrT homologs in Streptomyces avermitilis and Streptomyces coelicolor, it is believed that polyketide starter and extender units have a prevalent, crucial role as ligands in modulating antibiotic biosynthesis in actinomycetes. IMPORTANCE Numerous antibiotics are derived from polyketides, whose biosynthesis is accurately controlled by transcriptional regulators that respond to diverse physiological or environmental signals. It is generally accepted that antibiotics or biosynthetic intermediates serve as effectors to modulate their production in actinomycetes. Our study unprecedentedly demonstrates that the direct precursors of polyketide, propionyl-CoA and methylmalonyl-CoA, play a role as ligands to modulate erythromycin biosynthesis in Saccharopolyspora erythraea. More importantly, the two acyl-CoAs as ligands could adjust their own supplies by regulating the acetyl-CoA metabolic pathway so as to well settle the relationship between cellular growth and secondary metabolism. Significantly, polyketide starter and extender units have a universal role as ligands to coordinate antibiotic biosynthesis in actinomycetes. These findings not only expand the understanding of ligand-mediated regulation for antibiotic biosynthesis but also provide new insights into the physiological functions of polyketide starter and extender units in actinomycetes.

6.
Metabolism ; 124: 154874, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34517014

RESUMO

AIMS/HYPOTHESIS: We aimed to evaluate the effect of NAFLD on the risk of incident cardiovascular disease (CVD) and estimated glomerular filtration rate (eGFR)-based chronic kidney disease (CKD), and further test the joint effects and interactions between NAFLD status and individual metabolic element, as well as the total 'ABCs' metabolic goal achievement, on the CVD and CKD risk among 101,296 patients with prediabetes or diabetes from a prospective cohort study. METHODS: We conducted the study based on the China Cardiometabolic Disease and Cancer Cohort (4C) study, a large-scale, population-based prospective cohort. After excluding alcohol abuse and other cause of hepatic diseases, we used fatty liver index (FLI) ≥ 60 as a proxy of NAFLD and stratified the probability of fibrosis by aspartate transaminase/alanine transaminase ratio (AAR) with cut-offs of 0.8 and 1.4. 'ABCs' metabolic goal was defined as subjects who had HbA1c < 6.5% (A), SBP/DBP < 130/80 mmHg (B), and LDL-C < 100 mg/dL (C). During 3.8 years follow-up, we validated 2340 CVD events based on medical records and identified 1943 participants developed CKD based on centrally tested eGFR. RESULTS: The multivariable adjusted hazard ratios (HRs) were 1.15 (95% confidence interval (CI), 1.05-1.27) for CVD events and 1.33 (95% CI, 1.20-1.48) for CKD among NAFLD patients, compared with participants without NAFLD. Of NAFLD patients, relative to individuals with low AAR (<0.8), those with high AAR (≥1.4) were more likely to experience CVD events [1.62 (1.21-2.18)] and CKD [1.63 (1.17-2.28)]. Participants with NAFLD and comorbid poorly controlled metabolic risk factors had higher risk of CVD events or CKD than having either alone, with a significant interaction between poor glycemic control and NAFLD on the risk of vascular complications. CONCLUSIONS: NAFLD was associated with incident CVD and CKD among patients with prediabetes or diabetes. Such associations were substantially modified by the comprehensive achievement of metabolic goal.

7.
Bioengineered ; 12(1): 5950-5970, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34482803

RESUMO

Retinoblastoma is the most common intraocular malignancy during childhood. Currently, there is no effective treatment for metastatic retinoblastoma. We investigated potential biomarkers of retinoblastoma by utilizing three datasets from a public database. Functional enrichment analysis, including gene ontology, Kyoto encyclopedia of genes and genomes, gene set enrichment analysis and variation analysis, suggested that differentially expressed genes in retinoblastoma were enriched in accelerated cell cycle events. Protein-protein interaction analysis constructed a network consisting of six hub genes, including benzimidazoles 1 (BUB1), cyclin dependent kinase 1 (CDK1), centromere protein E (CENPE), kinesin family member 20A (KIF20A), PDZ binding kinase (PBK), and targeting protein for xklp2 (TPX2). Drug sensitivity analysis showed that nelarabine was positively correlated with five hub genes. All six genes were expressed differently in six immune subtypes and were positively correlated with stemness indices in most human cancer types. Since CENPE is the least known hub gene in retinoblastoma, we further analyzed the potential non-coding RNAs and transcription factors that regulate CENPE and built interaction networks of competing endogenous RNA and transcription factors. Immune cell infiltration, especially by plasma and B cells, was enhanced in samples with high CENPE expression. Pan-cancer analysis illustrated that CENPE was highly expressed in a wide range of human tumors. In vitro validation revealed that CENPE was significantly upregulated at both the mRNA and protein levels in retinoblastoma cells. In conclusion, CENPE, along with other hub genes, could serve as a potential biomarker and intervention target for retinoblastoma.

8.
Blood Adv ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507352

RESUMO

Transplant-associated thrombotic microangiopathy (TA-TMA) is a potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Information on markers for early prognostication remains limited, and no predictive tools for TA-TMA are available. We attempt to develop and validate a prognostic model for TA-TMA. A total of 507 patients who developed TA-TMA following allo-HSCT were retrospectively identified and separated into a derivation cohort and a validation cohort according to the time of transplantation to perform external temporal validation. Patient age (OR 2.371, 95% CI 1.264-4.445), anemia (OR 2.836, 95% CI 1.566-5.138), severe thrombocytopenia (OR 3.871, 95% CI 2.156-6.950), elevated total bilirubin (OR 2.716, 95% CI 1.489-4.955) and proteinuria (OR 2.289, 95% CI 1.257-4.168) were identified as independent prognostic factors for the 6-month outcome of TA-TMA. A risk score model termed BATAP (Bilirubin, Age, Thrombocytopenia, Anemia, Proteinuria) was then constructed according to the regression coefficients. The validated c-statistics were 0.816 (95% CI 0.766-0.867) and 0.756 (95% CI 0.696-0.817) in the internal and external validation, respectively. Calibration plots indicated that the model-predicted probabilities correlated well with the actual observed frequencies. This predictive model may facilitate the prognostication of TA-TMA and contribute to the early identification of high-risk patients.

9.
J Diabetes ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34427386

RESUMO

BACKGROUND: Gestational hyperglycemia increases the risk of diabetes in later life. However, the risk of future cardiovascular diseases (CVD) related to gestational hyperglycemia remains inconclusive. The purpose of this study was to investigate the impact of gestational hyperglycemia on the subsequent risk of CVD and its modifying factors among elderly Chinese women. METHODS: We conducted a case-control study of elderly women from the baseline survey of Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. Women with gestational hyperglycemia (n = 82), and controls matched by age and study site (n = 410) were included. Information on CVD, including reported coronary heart disease, stroke, or myocardial infarction, was collected through an interviewer-assisted questionnaire. RESULTS: Women with gestational hyperglycemia were more likely to develop diabetes (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.50-4.18) and CVD (OR, 1.98; 95% CI, 1.05-3.74). Even without progressing to type 2 diabetes, gestational hyperglycemia was associated with an increased risk of CVD (OR, 2.88; 95% CI, 1.18-7.00). However, subgroup analysis indicated that compared with those without gestational hyperglycemia or hypertension, women with both gestational hyperglycemia and hypertension had higher risk of CVD (OR, 3.98; 95% CI, 1.65-9.58), whereas the risk estimate did not significantly change in women with gestational hyperglycemia alone (OR, 2.15; 95% CI, 0.71-6.57). Stratified analysis indicated that among those with overweight/obesity, inactive physical activity, or unhealthy dietary habits, gestational hyperglycemia increased the risk of CVD. CONCLUSIONS: In elderly Chinese women, gestational hyperglycemia was associated with an increased risk of CVD in later life. This association was independent of the progression to diabetes and might be modified by lifestyle factors and hypertension.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34448477

RESUMO

PURPOSE: Observational studies have associated obesity with chronic kidney disease (CKD) and arterial stiffness, but the causality remains unclear. We aimed to investigate the causality of obesity with CKD and arterial stiffness using Mendelian randomization (MR) analysis. METHODS: We genotyped 14 body mass index (BMI)-associated variants validated in East Asians in 11384 Chinese adults. A genetic risk score based on the 14 variants and the 14 individual single nucleotide polymorphisms were respectively used as instrumental variables (IVs). CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m 2. Arterial stiffness was defined as brachial-ankle pulse wave velocity >1550 cm/s. RESULTS: Using the genetic risk score as the IV, we demonstrated causal relations of each 1-standard deviation increment in BMI with CKD (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.11-5.00) and arterial stiffness (OR: 1.71; 95% CI: 1.22-2.39). Using the 14 single nucleotide polymorphisms individually as IVs, each 1-standard deviation increment in BMI casually associated with CKD (OR: 2.58; 95% CI: 1.39-4.79) and arterial stiffness (OR: 1.87; 95% CI: 1.24-2.81) in the inverse-variance weighted analysis, and MR-Egger regression revealed no evidence of horizontal pleiotropy (Both P for intercept≥0.34). The causality between obesity and CKD was validated in two-sample MR analysis among Europeans (681275 of Genetic Investigation of ANthropometric Traits and 133413 of CKD Genetics). CONCLUSIONS: This study provided novel insights into causality of obesity with CKD and arterial stiffness, highlighting the importance of weight management for primary prevention and control of subclinical vascular diseases.

11.
Curr Eye Res ; : 1-8, 2021 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-34334060

RESUMO

AIM OF THE STUDY: This study was aimed to investigate the growth patterns and the relationship of the eyeball and the orbit using computed tomography (CT)-based three-dimensional (3D) techniques. MATERIALS AND METHODS: A total of 175 Chinese patients who had undergone craniofacial or orbital CT scans were enrolled. This study only included data from the unaffected eye and orbit. Images were processed using 3D reconstruction to obtain the eyeball and the orbit parameters. RESULTS: In early postnatal years, the sizes of eyeball and orbit increased significantly with age (p < 0.001) and reached a turning point at a critical age (8.967 and 12.800 years for the eyeball and orbit volume, respectively). The orbital index and orbital depth index, showing the shape of the orbital aperture and walls, decreased significantly with age (p < 0.001). In all ages, the orbit size was correlated with eyeball size (p < 0.001). The eye-orbit index, equivalent to the ratio of eye volume to orbital volume, declined steadily with age (p < 0.001). CONCLUSIONS: The eyeball and orbit developed rapidly in early postnatal years, and then matured at a critical age. The eyeball size significantly contributed to the orbital growth; this contribution may be reduced as the eye-orbit index decreased with age. To the best of our knowledge, this is the first report on the growth and interrelation of the eyeball and the orbit using CT-based 3D techniques.

12.
Blood Adv ; 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34448835

RESUMO

Intracranial hemorrhage (ICH) is a rare but fatal central nervous system complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, factors that are predictive of early mortality in patients who develop ICH after undergoing allo-HSCT have not been systemically investigated. From January 2008 to June 2020, 70 allo-HSCT patients with ICH diagnosis formed the derivation cohort. Forty-one allo-HSCT patients with ICH diagnosis were collected from 12 other medical centers during the same period, and they comprised the external validation cohort. We used these 2 cohorts to develop and validate a grading scale that enables the prediction of 30-day mortality from ICH in all-HSCT patients. Four predictors, lactate dehydrogenase level, albumin level, white blood cell count and disease status, were retained in the multivariable logistic regression model, and a simplified grading scale, termed the LAWS score, was developed. The LAWS score was adequately calibrated (Hosmer-Lemeshow test, p>0.05) in both cohorts. It had good discrimination power in both the derivation cohort (C-statistic of 0.859, 95% CI 0.776-0.945) and the external validation cohort (C-statistic of 0.795, 95% CI 0.645-0.945). The LAWS score is the first scoring system capable of predicting the 30-day mortality from ICH in allo-HSCT patients. It showed good performance in identifying allo-HSCT patients at increased risk of early mortality after ICH diagnosis. We anticipate that it would help risk-stratify allo-HSCT patients with ICH and facilitate future studies on developing individualized and novel interventions for patients within different LAWS risk groups.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34239051

RESUMO

The objective of this study was to compare clinical outcomes between noninherited maternal antigen (NIMA)-mismatched and noninherited paternal antigen (NIPA)-mismatched haploidentical hematopoietic stem cell transplantation (haplo-HSCT) among patients with hematological malignancies and perform a subgroup analysis. We retrospectively analyzed 378 patients with hematological malignancies who received haplo-HSCT from NIMA-mismatched (n = 201) and NIPA-mismatched (n = 177) donors between January 2012 and December 2017. The cumulative incidence of 100-d grades II-IV acute graft-versus-host disease (aGVHD) (19.2% vs. 32.8%, P = 0.003) was significantly lower in NIMA mismatch. Multivariate analysis showed that NIMA mismatch was associated with lower incidence of grades II-IV aGVHD and better overall survival (OS) and disease-free survival (DFS). According to the subgroup analysis, the clinical outcomes of older and/or female NIMA mismatches were comparable to those of younger and/or male NIPA mismatches with respect to grades II-IV aGVHD, chronic GVHD (cGVHD), nonrelapse mortality (NRM), relapse, DFS, and OS. In conclusion, this study confirmed the NIMA effect on aGVHD and demonstrated that NIMA mismatch was associated with better survival. In the NIMA mismatch context, donor age and sex did not seem to influence haplo-HSCT, which provides a basis for the selection of sibling donors.

14.
J Diabetes ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34259386

RESUMO

BACKGROUND: Type 2 diabetes is increasingly diagnosed at a younger age worldwide and in China. Limited data are available regarding the association between age at diabetes diagnosis and risks of albuminuria. This study sought to examine the independent effect of age at diagnosis of type 2 diabetes on the risk of albuminuria. METHODS: We used data from a nationwide multicenter study with 207 961 participants in mainland China. Age, sex, and study site were matched for 31 366 screen-detected type 2 diabetes cases and 31 366 normal controls. Age, sex, study site, and diabetes duration were matched for 7490 self-reported type 2 diabetes cases and 7490 normal controls. Risks of having albuminuria in matched type 2 diabetes vs controls were examined using multivariable logistic regression analysis in strata of age at diabetes diagnosis. RESULTS: Although the absolute rate of albuminuria is higher in older adults, the odds ratio of albuminuria in type 2 diabetes vs matched controls decreased with increasing age at diagnosis. For participants with diabetes diagnosed at an age of <50, 50 to 59, 60 to 69, or ≥70 years, the multivariable adjusted risk of albuminuria increased by 81%, 60%, 45%, and 33% for screen-detected diabetes, and 135%, 121%, 90%, and 58% for self-reported diabetes compared with their normal controls, respectively. CONCLUSIONS: A younger age at diagnosis of type 2 diabetes is associated with a more significantly elevated risk of albuminuria than an older age at diagnosis in Chinese adults.

16.
EBioMedicine ; 69: 103471, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34229277

RESUMO

BACKGROUND: Metabolic syndrome (MetS) is highly related to the excessive accumulation of visceral adipose tissue (VAT). Quantitative measurements of VAT are commonly applied in clinical practice for measurement of metabolic risks; however, it remains largely unknown whether the texture of VAT can evaluate visceral adiposity, stratify MetS and predict surgery-induced weight loss effects. METHODS: 675 Chinese adult volunteers and 63 obese patients (with bariatric surgery) were enrolled. Texture features were extracted from VATs of the computed tomography (CT) scans and machine learning was applied to identify significant imaging biomarkers associated with metabolic-related traits. FINDINGS: Combined with sex, ten VAT texture features achieved areas under the curve (AUCs) of 0.872, 0.888, 0.961, and 0.947 for predicting the prevalence of insulin resistance, MetS, central obesity, and visceral obesity, respectively. A novel imaging biomarker, RunEntropy, was identified to be significantly associated with major metabolic outcomes and a 3.5-year follow-up in 338 volunteers demonstrated its long-term effectiveness. More importantly, the preoperative imaging biomarkers yielded high AUCs and accuracies for estimation of surgery responses, including the percentage of excess weight loss (%EWL) (0.867 and 74.6%), postoperative BMI group (0.930 and 76.1%), postoperative insulin resistance (0.947 and 88.9%), and excess visceral fat loss (the proportion of visceral fat reduced over 50%; 0.928 and 84.1%). INTERPRETATION: This study shows that the texture features of VAT have significant clinical implications in evaluating metabolic disorders and predicting surgery-induced weight loss effects. FUNDING: The complete list of funders can be found in the Acknowledgement section.


Assuntos
Cirurgia Bariátrica/efeitos adversos , Gordura Intra-Abdominal/diagnóstico por imagem , Doenças Metabólicas/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Perda de Peso , Adulto , Feminino , Humanos , Masculino
17.
Transplant Cell Ther ; 27(10): 870.e1-870.e7, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34229053

RESUMO

Late-onset severe pneumonia (LOSP) is defined as severe pneumonia developing during the late phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because of the high mortality in patients with LOSP, it is important to identify prognostic factors. In this study, we aimed to develop a risk score system with broad applicability that can help predict the risk of LOSP-associated mortality. We retrospectively analyzed 100 patients with LOSP after allo-HSCT between June 2009 and July 2017. The assessment variables included immune, nutritional, and metabolic parameters at the onset of LOSP. Of these 100 patients, 45 (45%) eventually died, and 55 (55%) were positive for organisms, most commonly viruses. In the multivariate analysis, higher monocyte count (≥0.20 × 109/L versus <0.20 × 109/L; P = .001), higher albumin level (≥30.5 g/L versus <30.5 g/L; P = .044), lower lactic dehydrogenase level (<250 U/L versus ≥250 U/L; P = .008) and lower blood urea nitrogen concentration (<7.2 mmol/L versus ≥7.2 mmol/L; P = .026) at the onset of LOSP were significantly associated with better 60-day survival. A risk score system based on the foregoing results showed that the probability of 60-day survival decreased with increasing risk factors, from 96.3% in the low-risk group to 49.1% in the intermediate-risk group and 12.5% in the high-risk group. Our results indicate that this scoring system using 4 variables can stratify patients with different probabilities of survival after LOSP, which suggests that patients' immune, nutritional, and metabolic status are crucial factors in determining outcome.

19.
Curr Med Sci ; 41(3): 443-453, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34185250

RESUMO

We performed a retrospective analysis to investigate dynamic peri-hematopoietic stem cell transplantation (HSCT) minimal/measurable residual disease (MRD) on outcomes in patients with T-cell acute lymphoblastic leukemia (T-ALL). A total of 271 patients were enrolled and classified into three groups: unchanged negative MRD pre- and post-HSCT group (group A), post-MRD non-increase group (group B), and post-MRD increase group (group C). The patients in group B and group C experienced a higher cumulative incidence of relapse (CIR) (42% vs. 71% vs. 16%, P<0.001) and lower leukemia-free survival (LFS) (46% vs. 21% vs. 70%, P<0.001) and overall survival (OS) (50% vs. 28% vs. 72%, P<0.001) than in group A, but there was no significant difference in non-relapse mortality (NRM) among three groups (14% vs. 12% vs. 8%, P=0.752). Multivariate analysis showed that dynamic peri-HSCT MRD was associated with CIR (HR=2.392, 95% CI, 1.816-3.151, P<0.001), LFS (HR=1.964, 95% CI, 1.546-2.496, P<0.001) and OS (HR=1.731, 95% CI, 1.348-2.222, P<0.001). We also established a risk scoring system based on dynamic peri-HSCT MRD combined with remission status pre-HSCT and onset of chronic graft-versus-host disease (GVHD). This risk scoring system could better distinguish CIR (c=0.730) than that for pre-HSCT MRD (c=0.562), post-HSCT MRD (c=0.616) and pre- and post-MRD dynamics (c=0.648). Our results confirm the outcome predictive value of dynamic peri-HSCT MRD either alone or in combination with other variables for patients with T-ALL.

20.
J Clin Endocrinol Metab ; 106(10): e3957-e3968, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34125886

RESUMO

CONTEXT: Little is known about the link between nonalcoholic fatty liver disease (NAFLD) evolution and incident chronic kidney disease (CKD). OBJECTIVE: We aim to assess the associations of NALFD status changes and NAFLD fibrosis progression with the risk of incident CKD. METHODS: We conducted a community-based prospective study that included participants aged 40 years or older and free of CKD at baseline in 2010, with follow-up evaluations after a mean of 4.4 years. NAFLD was diagnosed by ultrasonography and NAFLD fibrosis score (NFS) was used to evaluate fibrosis stage and progression. CKD was defined by estimated glomerular filtration rate or urine albumin-to-creatinine ratio. All the measurements were performed at baseline and follow-up examination. RESULTS: Among 4042 participants with 4 NAFLD status change groups, incident NAFLD was associated with an increased risk of incident CKD (odds ratio [OR] = 1.44; 95% CI, 1.003-2.06; P = 0.048) compared with non-NAFLD after adjustments for the confounders, including evolution of diabetes, hypertension, and obesity, in addition to the baseline levels. However, the risk of incident CKD was not significantly different between NAFLD resolution and persistent NAFLD. Among 534 participants in the persistent NAFLD group, fibrosis progression from low NFS to intermediate or high NFS was associated with a significantly increased risk of incident CKD compared with stable fibrosis in low NFS (OR = 2.82; 95% CI, 1.22-6.56; P = 0.016). CONCLUSION: NAFLD development and fibrosis progression are associated with increased risk of incident CKD.

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