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Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease.
Chandrasekaran, P, Han, Y, Zerbe, CS, Heller, T, DeRavin, SS, Kreuzberg, SA, Marciano, BE, Siu, Y, Jones, DR, Abraham, RS, et al
The Journal of allergy and clinical immunology. 2023;(6):1619-1633.e11
Abstract
BACKGROUND Chronic granulomatous disease (CGD) is caused by defects in any 1 of the 6 subunits forming the nicotinamide adenine dinucleotide phosphate oxidase complex 2 (NOX2), leading to severely reduced or absent phagocyte-derived reactive oxygen species production. Almost 50% of patients with CGD have inflammatory bowel disease (CGD-IBD). While conventional IBD therapies can treat CGD-IBD, their benefits must be weighed against the risk of infection. Understanding the impact of NOX2 defects on the intestinal microbiota may lead to the identification of novel CGD-IBD treatments. OBJECTIVE We sought to identify microbiome and metabolome signatures that can distinguish individuals with CGD and CGD-IBD. METHODS We conducted a cross-sectional observational study of 79 patients with CGD, 8 pathogenic variant carriers, and 19 healthy controls followed at the National Institutes of Health Clinical Center. We profiled the intestinal microbiome (amplicon sequencing) and stool metabolome, and validated our findings in a second cohort of 36 patients with CGD recruited through the Primary Immune Deficiency Treatment Consortium. RESULTS We identified distinct intestinal microbiome and metabolome profiles in patients with CGD compared to healthy individuals. We observed enrichment for Erysipelatoclostridium spp, Sellimonas spp, and Lachnoclostridium spp in CGD stool samples. Despite differences in bacterial alpha and beta diversity between the 2 cohorts, several taxa correlated significantly between both cohorts. We further demonstrated that patients with CGD-IBD have a distinct microbiome and metabolome profile compared to patients without CGD-IBD. CONCLUSION Intestinal microbiome and metabolome signatures distinguished patients with CGD and CGD-IBD, and identified potential biomarkers and therapeutic targets.
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Postoperative Outcomes Associated With Procedural Sedation Conducted by Physician and Nonphysician Anesthesia Providers: Findings From the Prospective, Observational African Surgical Outcomes Study.
van der Merwe, F, Vickery, NJ, Kluyts, HL, Yang, D, Han, Y, Munlemvo, DM, Ashebir, DZ, Mbwele, B, Forget, P, Basenero, A, et al
Anesthesia and analgesia. 2022;(2):250-263
Abstract
BACKGROUND There is an unmet need for essential surgical services in Africa. Limited anesthesia services are a contributing factor. Nonphysician anesthesia providers are utilized to assist with providing anesthesia and procedural sedation to make essential surgeries available. There is a paucity of data on outcomes following procedural sedation for surgery in Africa. We investigated the postoperative outcomes following procedural sedation by nonphysicians and physicians in Africa. We hypothesized that the level of training of the sedation provider may be associated with the incidence of severe postoperative complications and death. METHODS A secondary analysis of a prospective cohort of inhospital adult surgical patients representing 25 African countries was performed. The primary outcome was a collapsed composite of inhospital severe postoperative complications and death. We assessed the association between receiving procedural sedation conducted by a nonphysician (versus physician) and the composite outcome using logistic regression. We used the inverse probability of treatment weighting propensity score method to adjust for potential confounding variables including patient age, hemoglobin level, American Society of Anesthesiologists (ASA) physiological status, diabetes mellitus, urgency of surgery, severity of surgery, indication for surgery, surgical discipline, seniority of the surgical team, hospital level of specialization, and hospital funding system using public or private funding. All patients who only received procedural sedation for surgery were included. RESULTS Three hundred thirty-six patients met the inclusion criteria, of which 98 (29.2%) received sedation from a nonphysician provider. The incidence of severe postoperative complications and death was 10 of 98 (10.2%) in the nonphysician group and 5 of 238 (2.1%) in the physician group. The estimated association between procedural sedation conducted by a nonphysician provider and inhospital outcomes was an 8-fold increase in the odds of severe complications and/or death, with an odds ratio (95% confidence interval [CI]) of 8.3 (2.7-25.6). CONCLUSIONS The modest number of observations in this secondary data analysis suggests that shifting the task of procedural sedation from physicians to nonphysicians to increase access to care may be associated with severe postoperative complications and death in Africa. Research focusing on identifying factors contributing to adverse outcomes associated with procedural sedation is necessary to make this practice safer.
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Serum Ceruloplasmin Is the Candidate Predictive Biomarker for Acute Aortic Dissection and Is Related to Thrombosed False Lumen: a Propensity Score-Matched Observational Case-Control Study.
Ma, C, Zhao, H, Shi, F, Li, M, Liu, X, Ji, C, Han, Y
Biological trace element research. 2021;(3):895-911
Abstract
Acute aortic dissection (AAD), one of the fatal diseases observed at the department of vascular surgery, is associated with a great mortality rate at the early stage. Ceruloplasmin (CP) is the plasma protein that functions as a copper transporter. The current retrospective research was carried out to assess CP contents and to examine the possible part in diagnosing patients with AAD. In addition, propensity score matching (PSM) was also utilized for reducing the bias in case screening as well as the clinical confounders. Using PSM, this study included 85 pairs of AAD cases (Stanford A and B dissection) and matched controls, and their CP levels were also detected through enzyme-linked immunosorbent assay (ELISA). Additionally, the relative clinical data were extracted from participants included in this study. After PSM adjustment for clinical variables, including gender, age, body mass index (BMI), heart ratio (HR), smoking, hypertension, diabetes mellitus, coronary heart disease (CHD), and stroke, the serum CP contents among AAD cases were remarkably increased compared with those among the normal subjects. Besides, the CP contents showed independent association with the AAD risk. Typically, the CP level was significantly positively correlated with platelet (R = 0.329) or C-reactive protein (R = 0.340) level. Meanwhile, the area under the receiver operating characteristic (ROC) curve (AUC) was 0.929 when CP was used to diagnose AAD, and the best threshold value was 36.82mg/dL. Serum CP content significantly increased in cases with thrombosed false lumen (FL) relative to those in patent FL cases. Results of logistic regression analysis suggested that a greater CP content indicated an increased thrombosed FL risk (OR = 1.11; 95% CI: 1.01-1.23; P = 0.040). Findings in this study suggest that serum ceruloplasmin contents evidently increased among acute aortic dissection cases. CP shows close correlation with the inflammatory factors among AAD cases. Further, CP may serve as the candidate biomarker to diagnose AAD and to identify an increased risk of thrombosed false lumen.
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Association of healthy lifestyle including a healthy sleep pattern with incident type 2 diabetes mellitus among individuals with hypertension.
Song, Z, Yang, R, Wang, W, Huang, N, Zhuang, Z, Han, Y, Qi, L, Xu, M, Tang, YD, Huang, T
Cardiovascular diabetology. 2021;(1):239
Abstract
BACKGROUND Evidence is limited regarding the association of healthy lifestyle including sleep pattern with the risk of complicated type 2 diabetes mellitus (T2DM) among patients with hypertension. We aimed to investigate the associations of an overall healthy lifestyle including a healthy sleep pattern with subsequent development of T2DM among participants with hypertension compared to normotension, and to estimate how much of that risk could be prevented. METHODS This study examined six lifestyle factors with T2DM cases among hypertension (227,966) and normotension (203,005) and their interaction in the UK Biobank. Low-risk lifestyle factors were defined as standard body mass index (BMI), drinking alcohol in moderation, nonsmoking, engaging in moderate- to vigorous-intensity physical activity, eating a high-quality diet, and maintaining a healthy sleep pattern. RESULTS There were 12,403 incident T2DM cases during an average of 8.63 years of follow-up. Compared to those with 0 low-risk lifestyle factors, HRs for those with 5-6 were 0.14 (95% CI 0.10 to 0.19) for hypertensive participants, 0.13 (95% CI 0.08 to 0.19) for normotensive participants, respectively (ptrend < 0.001). 76.93% of hypertensive participants were considerably less likely to develop T2DM if they adhered to five healthy lifestyle practices, increased to 81.14% if they followed 6-factors (with a healthy sleep pattern). Compared with hypertension adults, normotensive people gain more benefits if they stick to six healthy lifestyles [Population attributable risk (PAR%) 83.66%, 95% CI 79.45 to 87.00%, p for interaction = 0.0011]. CONCLUSIONS Adherence to a healthy lifestyle pattern including a healthy sleep pattern is associated with lower risk of T2DM in hypertensives, and this benefit is even further in normotensives.
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Nomogram predicted disease free survival for colorectal liver metastasis patients with preoperative chemotherapy followed by hepatic resection.
Liu, W, Wang, K, Han, Y, Liang, JY, Li, YH, Xing, BC
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2019;(11):2070-2077
Abstract
BACKGROUND Hepatic resection is regarded to as a potentially curative option for colorectal cancer liver metastases (CRLM), but it is associated with a high rate of recurrence. The present study intended to establish an effective nomogram to predict disease free survival (DFS) and select candidates of hepatic resection. METHODS The nomogram was based on a retrospective study on 447 CRLM patients treated with preoperative chemotherapy followed by hepatic resection using a multicentric database between January 1st, 2010 and December 31st, 2017. Results were validated using bootstrap resampling on 117 patients. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. Overall survival, disease free survival, and local recurrence rate for patients with colorectal cancer were measured. RESULTS Based on multivariate analysis of the primary cohort, independent factors for DFS included tumor size larger than 5 cm, multiple liver metastases(>1), RAS mutation, primary lymph node metastasis and tumor size increase after preoperative chemotherapy. These five factors were all considered in the nomogram. The C-index of the nomogram for predicting survival was 0.675. With external validation, the C-index of the nomogram for the prediction of the DFS was 0.77, which demonstrated that this model has a good level of discriminative ability. For the 382 patients (66.7%) who developed recurrence, the optimal cutoff point for early recurrence was determined to be 12 months after hepatic resection. CONCLUSIONS The proposed nomogram demonstrated accurate prognostic prediction of DFS for CRLM patients with preoperative chemotherapy followed by hepatic resection.
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Clinical outcomes of comorbid cancer patients with venous thromboembolism: A retrospective, single-center study in Korea.
Jeong, J, Jeong, MJ, Choi, K, Kim, MJ, Han, Y, Kwon, TW, Cho, YP
Medicine. 2019;(37):e17181
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Abstract
In this single-center, retrospective study, we aimed to report the clinical outcomes, among Asian comorbid cancer patients with venous thromboembolism (VTE), and compare them with those of VTE patients without cancer.Between January 2013 and December 2017, a total of 322 consecutive patients-diagnosed with acute VTE involving the leg, pelvis, or lung-were screened for inclusion. Comorbid cancer patients with VTE (n = 135, 41.9%) were included in this study and analyzed in comparison with VTE patients without cancer (n = 187, 58.1%). The study outcomes were the composite incidence of symptomatic and radiologically confirmed recurrence of VTE, or any-cause mortality.The study outcome incidence was 62.2% (n = 84) during a mean follow-up period of 10 months: VTE recurrence in 7 patients and any-cause mortality in 83. Upon multivariate analysis, higher body mass index, diabetes mellitus, cancer stage IV, and radiotherapy were independently associated with study outcome incidence. VTE involving the inferior vena cava (hazard ratio [HR], 12.1; 95% confidence interval [CI], 1.20-120.80; P = .034), lung cancer (HR, 16.5; 95% CI, 2.32-117.50; P = .005), and use of vitamin K antagonists (HR, 36.4; 95% CI, 3.00-442.70; P = .005) were independent predictors of VTE recurrence. Compared with VTE patients without cancer, the study outcome incidence was significantly higher among comorbid cancer patients with VTE (62.2% vs 7.5%, P < .001), although there was no significant difference in VTE recurrence between the 2 groups (5.2% in patients with cancer vs 3.7% in patients without cancer, P = .531).We found that various cancer-related and patient-related factors were associated with outcomes among comorbid cancer patients with VTE. The composite incidence of VTE recurrence or any-cause mortality was significantly higher among cancer patients with VTE than among VTE patients without cancer.
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Risk of major adverse cardiovascular events in subjects with asymptomatic mild carotid artery stenosis.
Kwon, H, Kim, HK, Kwon, SU, Lee, SW, Kim, MJ, Park, JW, Noh, M, Han, Y, Kwon, TW, Cho, YP
Scientific reports. 2018;(1):4700
Abstract
This study aimed to test the hypothesis that the risk of major adverse cardiovascular events (MACE) is similar for subjects with asymptomatic mild and moderate carotid artery stenosis (CAS). We enrolled a total of 453 subjects with asymptomatic CAS (30-69%) detected on baseline screening Doppler ultrasound (DUS) examination between January 2008 and December 2010. The follow-up DUS findings and MACE occurrence (fatal or nonfatal myocardial infarction or stroke and all-cause mortality) were compared between subjects with mild (30-49%) and moderate (50-69%) CAS during the 8-year follow-up period. There was no significant difference in the occurrence of MACE between subjects with mild (n = 289) and moderate (n = 164) CAS (13.8% vs. 15.9%, respectively; p = 0.56), although there was a nonsignificant trend toward an increased risk of major ipsilateral stroke in subjects with moderate CAS (1.4% vs. 4.3%; p = 0.06). Multivariate regression analysis indicated that worsening CAS was independently associated with MACE occurrence (hazard ratio [HR], 4.40; 95% confidence interval [CI], 2.65-7.27; p < 0.01), whereas an increased serum high-density lipoprotein cholesterol level was correlated with a decreased risk of MACE (HR, 0.42; 95% CI, 0.23-0.75; p < 0.01). The cumulative risk of MACE in subjects with asymptomatic mild CAS is similar to that in subjects with asymptomatic moderate CAS.
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Association study of gut flora in Wilson's disease through high-throughput sequencing.
Geng, H, Shu, S, Dong, J, Li, H, Xu, C, Han, Y, Hu, J, Han, Y, Yang, R, Cheng, N
Medicine. 2018;(31):e11743
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Abstract
In this study, we analyzed the difference of intestinal flora polymorphisms between Wilson's disease (WD) patients and healthy people by high-throughput sequencing technology, and explored the correlation between WD and intestinal flora polymorphism.A total of 22 cases of WD patients and 22 healthy persons as control were recruited. The total DNA was extracted from the fecal specimens of all the subjects, V4 high variable region of 16S rRNA gene was amplified and sequenced by high-throughput sequencing. The sequencing results were analyzed by α diversity and β diversity. The unweighted UniFrac distance matrices were calculated and trees were built by unweighted-pair group method with arithmetic mean (UPGMA).A total of 2,548,262 sequences were obtained after the data are optimized, the average sequences in the WD group was 36,836 ± 4104 and it was 35,051 ± 3075 in the normal control group, there was no significant difference in the average sequence number between the 2 groups. OTU analysis showed that 2663 OTU were obtained in WD group, and 3271 OTU were obtained in the control group, of which 941 were common OTU. Colony diversity analysis showed that the intestinal flora of WD group and control group belonged to 5 phyla, they were Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria, and Tenericutes, respectively. In WD group, the abundance of Bacteroidetes was significantly lower than that of the control group (67.19% vs 76.75%, P < .001), and the abundance of Firmicutes (26.18% vs 19.83%, P < .001), Proteobacteria (4.31% vs 3.09%, P < .05), Fusobacteria (1.88% vs 0.04%, P < .001) were significantly higher than that of control group. Compared with the control group at the level of the genus, the abundance of Bacteroides (4.85% vs 4.6%, P < .05), Faecalibacterium (2.92% vs 2.13%, P < .05), Megamonas (0.84% vs 0.22%, P < .001), Lachnospira (0.16% vs 0.09%, P < .001) significantly increased in WD group, while the abundance of Prevotella (1.63% vs 2.48%, P < .001), Roseburia (0.75% vs 1.39%, P < .001) and Phascolarctobacterium (1.72% vs 2.45%, P < .001) significantly decreased in WD group. PCoA and UPGMA tree analysis showed that there were significant differences of gut microbial compositions between the 2 groups.The diversity and composition of intestinal flora in the WD patients were significantly lower than those in the healthy controls, and the diversity of intestinal flora may be associated with the presence of WD.
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Erectile dysfunction in patients with plaque psoriasis: the relation of depression and cardiovascular factors.
Ji, S, Zang, Z, Ma, H, Gu, M, Han, Y, Wang, L, Jia, S, Yang, B
International journal of impotence research. 2016;(3):96-100
Abstract
Psoriasis is a chronic inflammatory skin disease and seems to be associated with erectile dysfunction (ED). ED is a predictor of future cardiovascular disease. It is important to identify ED early and investigate cardiovascular problems in psoriasis patients. The sample consisted of 191 psoriasis patients and 191 healthy men. One hundred and one of 191 (52.9%) patients with psoriasis were indicative of ED, compared with 40.3% in control group, reflecting an age-adjusted odds ratio of 1.965 in favor of the psoriasis group. A univariate analysis in the psoriasis group indicated that age, hypertension, hyperlipidemia, diabetes mellitus and depressive symptoms were the risk factors for ED. The multivariate logistic regression model indicated that increasing age, hypertension, hyperlipidemia and depressive symptoms were independent risk factors for ED in psoriasis. The more severe depressive symptoms increased the risk of ED and especially moderate-severe ED. The diagnosis of ED may help prevent emotional and physical discomfort in men and aid in identifying reversible cardiovascular risk factors. Screening of ED may become a part of routine care in the management of psoriasis patients.
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Bone turnover and bone mineral density in HIV-1 infected Chinese taking highly active antiretroviral therapy -a prospective observational study.
Zhang, L, Su, Y, Hsieh, E, Xia, W, Xie, J, Han, Y, Cao, Y, Li, Y, Song, X, Zhu, T, et al
BMC musculoskeletal disorders. 2013;:224
Abstract
BACKGROUND Low bone mass and high bone turnover have been reported in HIV-infected individuals, both as a consequence of HIV infection itself, as well as from treatment with highly active antiretroviral therapy (HAART). The purpose of this study is to evaluate the impact of HAART on bone mineral density and bone turnover in HIV-1 infected Chinese patients. METHODS Forty HIV-1 infected patients were enrolled in this study; all patients were followed through 48 weeks, and 17 patients completed 96 weeks. Bone mineral density (BMD), procollagen type 1 N-terminal propeptide (P1NP), collagen type 1 cross-linked C-telopeptide (β-CTX), parathyroid hormone (PTH), and 25-OH vitamin D levels were measured at baseline, 48 and 96 weeks. Baseline measurements were compared with an age-, gender-, and BMI-matched healthy control population. RESULTS At baseline, raw BMD in the lumbar spine of HIV-1 infected patients was significantly lower than that of healthy controls (1.138 ± 0.112 g/cm2 vs. 1.195 ± 0.139 g/cm2, p = 0.047). During the first 48 weeks after initiating HAART, BMD of lumbar spine, femoral neck, and total hip decreased significantly in HIV-1 infected patients, with annual percent decline ranging from 1.78-3.28%. However, from week 48 to 96, BMD remained stable. Baseline levels of β-CTX (0.31 ± 0.16 ng/mL vs. 0.42 ± 0.19 ng/mL, p = 0.008) and P1NP (32.96 ± 14.00 ng/mL vs. 55.82 ± 26.87 ng/mL, p = 0.05) were lower in HIV-infected patients compared with controls, respectively. Both β-CTX and P1NP levels increased after onset of HAART until week 48, and remained elevated during the next 48 weeks. 25-OH vitamin D in HIV-infected patients was lower at baseline compared to healthy controls, but this difference was not statistically significant. PTH, however, was higher in HIV patients at baseline, and showed a significant increase throughout the study. CONCLUSIONS Chinese adults with HIV-1 infection have low bone turnover prior to HAART as well as lower raw BMD of the lumbar spine compared with healthy controls, with further bone loss occurring following the initiation of HAART. The long-term clinical implications of these findings remain unclear at this time.