Surface charge and hydrophobic properties of fresh and cryopreserved blood phagocytes as determined by partition in two-phase aqueous polymer systems

Cell partitioning in two-phase aqueous polymer systems was used to examine hydrophobic and surface charge-related membrane properties of fresh and cryopreserved human blood phagocytes. This technique is highly sensitive to cell surface characteristics, and the partition behavior depends exponentially on the membrane properties involved. The transition from fresh to cryopreserved and reconstituted cells was accompanied by a significant loss of net negative charge without detectable alteration in hydrophobic membrane properties as detected by the partition technique. The partition coefficient (PC), which is the proportion of cells partitioning into the upper phase, when measured for fresh cells mixed with dimethyl sulfoxide (Me2SO) and cryopreserved leukocytes. No difference was detected between the PCs of the total leukocytes and phagocytes as determined by differential leukocyte counts of the upper polymer phase. The significantly reduced PC of cells prepared by dextran (Dx) separation in both charge-sensitive and -insensitive systems is attributable to the capacity of Dx to adsorb, in part irreversibly, to cells so that those carrying Dx tend to partition with Dx in the lower phase. These results serve to illustrate the utility of partitioning as a highly sensitive method to probe leukocyte surface membrane properties.     

The effect of anti-IL-10 on proliferation and cytokine production in human schistosomiasis: fresh versus cryopreserved cells

In this study we neutralized endogenous IL-10 in PBMC from individuals chronically infected with Schistosoma haematobium by using anti-IL-10 MoAbs, and examined the effect and adult worm antigen (AWA)-specific responses in both fresh or cryopreserved cells. Anti-IL-10 alone increased background proliferation of PBMC, but did not augment the AWA-specific responses in either fresh or frozen cells. In freshly isolated PBMC, IFN-γ production in response to AWA was enhanced significantly in the presence of anti-IL-10. In cryopreserved cells, the augmentation of IFN-γ in the presence of anti-IL-10 was four-fold less than in the freshly-isolated cells. Neutralization of IL-10 had no effect on IL-4 production. These data show that IL-10 plays a role in specifically down-regulating Th1- but not Th2-type responses and, in contrast to previous reports, anti-IL-10 does not augment proliferation to parasite antigen in chronic schistosomiasis .     

急性白血病化疗后输注冻存自体血小板20例临床观察

血小板减少症是急性白血病(AL)化疗后常见、严重的并发症,可危及患者生命,通常需即时输注异体血小板治疗,但存在输血反应、输血相关性移植物抗宿主病(TA-GVHD)、输血传播性疾病、输注无效等副反应。本研究应用深低温冻存自体血小板输注治疗AL化疗后血小板减少症,并检测其功能,观察临床效果,报道如下。     

高龄女性IVF/ICSI助孕临床妊娠结局影响因素研究

目的探讨高龄女性行体外受精或卵泡浆内单精子显微注射技术(IVF/ICSI)助孕临床妊娠结局的影响因素,为高龄女性提供合理的助孕建议。方法回顾性分析2016-01~2018-12在南宁市某三甲医院生殖中心行IVF/ICSI治疗的633个周期助孕资料,依据妊娠结局分为临床妊娠组(182个周期)和未孕组(451个周期)。采用多因素Logistic回归分析妊娠结局的影响因素。结果女方年龄大(OR=0.682,95%CI=0.604~0.770)、有剖宫产史(OR=0.411,95%CI=0.232~0.729)、有痛经史(OR=0.257,95%CI=0.074~0.893),妊娠率降低;窦卵泡数多(OR=1.052,95%CI=1.010~1.096)、移植胚胎质量高(OR=1.310,95%CI=1.032~1.664),妊娠率增高。结论广大女性应当合理规划生育年龄,从自身预防高龄不孕症的发生。助孕机构应当对高龄助孕女性的健康状况、生育力进行细致全面地评估,对生育几率、生育风险进行客观充分地告知,综合各方面为高龄女性制定安全合理的助孕方案。     

Impact of triglyceride-glucose index on long-term cardiovascular outcomes in patients with myocardial infarction with nonobstructive coronary arteries

Background and aimsTriglyceride-glucose (TyG) index has been reported as a novel surrogate marker of insulin resistance and a risk factor in patients with coronary artery disease. We aimed to investigate the prognostic value of TyG index in a distinct entity with myocardial infarction with nonobstructive coronary arteries (MINOCA).Methods and resultsA total of 1179 MINOCA patients were recruited and divided according to tertile levels of TyG index. The primary endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, reinfarction, stroke, revascularization and hospitalization for unstable angina or heart failure. Kaplan–Meier, Cox regression and receiver-operating characteristic analyses were performed. Patients with higher tertiles of TyG index had a significantly higher incidence of MACE (9.6%, 14.9%, 18.0%; p = 0.003) over the median follow-up of 41.7 months. After multivariate adjustment, elevated TyG index was significantly associated with an increased risk of MACE (HR 1.33, 95% CI: 1.04–1.69, p = 0.020). The adjusted risk of MACE also increased with rising tertiles of TyG index (tertile 1 as reference; tertile 2: HR 1.64, 95% CI: 1.06–2.53, p = 0.025; tertile 3: HR 1.85, 95% CI: 1.17–2.93, p = 0.008). The TyG index remained a robust risk factor in overall and subgroups of MINOCA patients (all p < 0.05). Moreover, the TyG index yielded a moderate predictive value of MACE (area under the curve 0.66, 95% CI:0.61–0.71, p < 0.001).ConclusionElevated TyG index was independently associated with a poor prognosis after MINOCA. Routine assessment of TyG index may improve risk stratification and facilitate decision making in MINOCA patients.     

Long‐term outcomes in patients with normal coronary arteries,nonobstructive, or obstructive coronary artery disease on invasive coronary angiography

BackgroundNormal or near normal coronary arteries (NNCA) or nonobstructive coronary artery disease (CAD) are commonly found on invasive coronary angiography (ICA).HypothesisWe aimed to determine long‐term outcomes by severity of CAD in a contemporary cohort of patients undergoing ICA for evaluation for ischemic heart disease.MethodsWe assessed a consecutive cohort of 925 patients who underwent non‐emergent ICA over 24 months. Cardiac death (CD), nonfatal myocardial infarction (NFMI), late revascularization, and medication use were assessed.ResultsFollow‐up data was available in 850 patients. Of patients without heart failure, at a median of 6.0 years, there was a significant decrease in survival free from CD or NFMI, and from all cardiac events, for those with obstructive CAD compared with patients with NNCAs or nonobstructive CAD (p < .001 for both). No differences between NNCA and nonobstructive CAD patients in rates of CD or NFMI (2.0% vs. 2.1%/year, p = .58) or all cardiac events (2.4% vs. 2.9%/year, p = .84) were observed.ConclusionLong‐term follow‐up in a contemporary cohort of consecutive patients undergoing non‐emergent ICA for detection of CAD showed no difference in annual rates of CD or NFMI, or total cardiac events, in patients with NNCAs versus those with nonobstructive CAD, whereas patients with obstructive CAD had significantly more events. Event rates were low and similar by gender. Use of aspirin, lipid lowering therapy, and beta‐blockers increased in all subgroups after ICA. We speculate this may explain the low incidence of subsequent cardiac events, and similar event rates in patients with NNCA and nonobstructive CAD, even in patients presenting with non‐ST‐elevation MI.     

Effect of nonobstructive coronary stenosis on coronary microvascular dysfunction and long‐term outcomes in patients with INOCA

BackgroundIschemic pain with no‐obstructive coronary artery (INOCA) is clinically significant and defined by nonobstructive coronary stenosis <50%. Coronary microvascular dysfunction (CMD) is a relevant cause associated with adverse outcomes.ObjectivesInvestigated the effect of no‐stenosis (0% stenosis) and non‐obstructive (0% < stenosis < 50%) on the prognostic impact of CMD in INOCA.MethodA retrospective study assessed the coronary microvascular function in 151 INOCA patients who underwent invasive angiography by the coronary angiography‐derived index of microcirculation‐resistance (caIMR). CZT‐SPECT was performed to evaluate myocardial perfusion imaging (MPI) abnormalities. Chi‐square test/Fisher exact test, Student t‐test, Kaplan–Meier curve, and Uni‐multivariable Cox proportional models were used for analysis. Clinical outcomes were major adverse cardiovascular events (MACE) during a median follow‐up of 35 months.ResultNo‐stenosis was present in 71 (47%) INOCA patients, and 80 (53%) were with nonobstructive. CMD (caIMR ≥ 25) was more prevalent in patients with no‐stenosis than nonobstructive (76.1% vs. 48.8%, p = .001), along with abnormal MPI (39.4% vs. 22.5%, p = .024). The MACE rates were not different between no‐stenosis and nonobstructive stenosis. CMD showed an increased risk of MACE for all INOCA. No‐stenosis with CMD had the worst prognosis. Cox regression analysis identified CMD and abnormal MPI as predictors of MACE in all INOCA and patients with no‐stenosis. However, no‐stenosis and nonobstructive stenosis were not predictors of MACE in INOCA.ConclusionCMD was more frequently present in INOCA with no‐stenosis. However, there was no difference in long‐term clinical outcomes between no‐stenosis and nonobstructive stenosis. CMD could independently predict poor outcomes in INOCA, particularly in patients with no‐stenosis.     

Functional hepatic recovery after xenotransplantation of cryopreserved fetal liver cells or soluble cell-factor administration in a cirrhotic rat model: Are viable cells necessary?

Background and Aim:  Chronic liver failure results in the decrease of the number of functioning hepatocytes. It dictates the necessity of using exogenous viable cells or/and agents that can stimulate hepatic regenerative processes. Fetal liver contains both hepatic and hematopoietic stem cells with high proliferative potential, which may replace damaged cells. Also, immature cells produce fetal-specific factors which may support the injured liver. Our aim was to test the ability of human fetal liver cells and cell-free fetal-specific factors of non-hepatic origin to stimulate recovery processes in an experimental model of carbon tetrachloride–induced cirrhosis in rats.
Methods:  Cirrhotic rats were intrasplenically injected with fetal liver cells (1 × 10⁷ cells/0.3 mL medium) or cell-free fetal-specific factors (0.3 mL/1 mg protein). Control groups received medium alone. Serum indexes, hepatic functions, and morphology were evaluated for 15 days.
Result:  Human fetal liver cell transplantation was shown to abrogate the mortality of cirrhotic animals, to improve serum markers, and to restore liver mitochondrial function and detoxification. Morphological patterns of liver recovery were observed by histology. In comparison, an injection of fetal-specific factors produced similar functional recovery, whilst a more limited liver regeneration was observed by histology.
Conclusions:  The positive effects of fetal liver cell and cell-free fetal-specific factors in experimental cirrhosis may result from the presence of stage-specific factors activating hepatocellular repair.     

Cryopreservation of the bone marrow from patients with acute myeloid leukaemia leads to functional abnormalities

We compared the performance of the stroma (SL) and haematopoietic progenitors before (group A) or following cryopreservation from patients in complete remission (CR) of acute myeloid leukaemia before autologous transplantation (AML) (group B), to similarly treated normal cells (groups A and B). From each group, fibroblastic (F) colony-forming units (CFU) and SL were established and their growth quantitated. Upon confluence of SL, 1 x 10(4)selected CD34+ cells from patient or control samples (of group A and B) were seeded on pre-formed SL from AML or control group A and B layers and adhesive precursors were scored for the formation of blastic (-b1) CFU (>20 cells). Lastly, CD34+ cells from the 4 progenitor sources were cultured in the presence of growth factors and scored for the production of granulocyte-macrophage (GM) CFU, erythroid burst forming units (BFU-E) and mixed colonies (CFU-MIX). In the patients, CFU-F numbers were decreased and by 5 wk SL failed to reach confluence. Group A AML CD34+ progenitors gave a mean of 119.2 (SD 80.4) CFU-bl/10(4) CD34+ cells, but following cryopreservation these numbers declined (83.2, SD 72.71; p = 0.009). Although AML SL prior to cryopreservation supported control CFU-bl adequately, contrary to the norm, this property decreased in group B stroma (mean 50.9/10(4)CD34+ cells, SD 49.33; p =(0.02). Group B AML samples gave significantly fewer CFU-MIX and BFU-E than pre-freezing cultures and than control samples at the first 2-growth factor combination but numbers improved following further addition of cytokines. We conclude that cryopreservation of the bone marrow of patients in CR of AML results in an inhibition of the proliferation of the CD34+ precursors. It also modifies the stroma, leading to reductions in the support of normal clones.     

Platelet characteristic antigens of CD34+ cells in cryopreserved cord blood: a study of platelet-derived microparticles in transplant processing

BACKGROUND AND OBJECTIVES: In previous studies, we found that platelet microparticles (PMPs) bind to cord blood (CB) CD34+ cells and transfer adhesion molecules to them, which enhances their engraftment. Before applying this phenomenon in actual transplants, we investigated the effect of PMPs on cryopreserved CD34+ cells in CB. MATERIALS AND METHODS: We cryopreserved 18 CB units, then evaluated the binding of PMPs to CD34+ cells after thawing, by varying the expression of platelet characteristic antigens (CD41a, CD61, CD62P and CXCR4) on these cells. Adherence of the CD34+ cells, coated with freeze/thaw-induced PMPs, to endothelium and fibronectin was also studied, as were the effects of thrombin-induced PMPs from both fresh and preserved CB platelets. RESULTS: PMPs induced by freezing and thawing adhered less well to CD34+ cells than did those from fresh CB, and cells coated with these PMPs had poor adherence. However, thrombin-induced PMPs from both fresh and preserved CB platelets bound equally well to cryopreserved CD34+ cells and improved their adhesion properties. CONCLUSIONS: PMPs could be a useful tool for enhancing engraftment after CB transplantation.     

Pregnancy outcomes in patients treated with belimumab: Report from real-world experience

ObjectiveTo investigate the neonatal and maternal outcomes of patients treated with belimumab during pregnancy.Materials and methodsWe retrospectively collected patients who were treated with belimumab during pregnancy from January 2018 to October 2020 in a tertiary referral hospital in Taiwan. All patients had clinical and serological features of systemic lupus erythematosus or antiphospholipid syndrome and had been treated accordingly. The patients’ medical and obstetric history, obstetric complications and fetal outcomes were collected by chart review.ResultsA total of 13 pregnancies in 13 patients were included. The median age was 38 years (interquartile range 32–41 years), 46.2% had a history of recurrent pregnancy loss, and the median number of treatment courses with belimumab (400 mg per dose) was two. There were 11 live births (84.6%, 11 of 13). One episode of omphalitis was noted in one fetus, who recovered well with antibiotic treatment. No fetus had leukopenia, lymphopenia, neutropenia, or thrombocytopenia in the days after birth. No fetal anomalies were found in this series. Among the six patients with a past history of recurrent pregnancy loss, four had live births.ConclusionThis study provides new evidence for the use of belimumab in pregnant patients. No increase in the risk of fetal anomalies or severe infection was noted in the patients who were exposed to belimumab during pregnancy. Cautious monitoring is necessary if belimumab is used in pregnant patients, and more data are still needed to validate its safety.     

Meta-analysis of cardiovascular outcomes with dronedarone in patients with atrial fibrillation or heart failure

Dronedarone is a benzofuran derivative approved by the Food and Drug Administration to decrease the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) and associated cardiovascular risk factors who are in sinus rhythm or will undergo cardioversion. There has been recent evidence to suggest that dronedarone may not have a favorable safety profile. We decided to evaluate all available evidence on the cardiovascular safety of this drug. A systematic search was made of the PubMed, CENTRAL, and EMBASE databases for randomized controlled trials from 1966 through 2011 comparing dronedarone to comparators in AF/heart failure. Intervention was dronedarone for AF for some studies and heart failure for others. Comparators included standard medical therapy and/or placebo and amiodarone for 1 study. Outcomes assessed were all-cause mortality, cardiovascular mortality, ventricular arrhythmias, embolic events, acute coronary syndrome, heart failure exacerbations, and hospitalization rates in the intervention versus comparator group at the end of ≥ 3 months of follow up with abstraction of data by 1 author. Seven randomized controlled trials were included in our analysis. Dronedarone use was associated with a trend toward worse all-cause and cardiovascular mortalities and increased heart failure exacerbations. It also showed numerically higher event rates for all other outcome events except acute coronary syndrome. Our pooled analysis showed increased all-cause and cardiovascular mortalities and increased heart failure exacerbations with use of dronedarone across a wide spectrum of populations. In conclusion, we recommend exercising caution using dronedarone, especially in patients with cardiovascular risk factors.     

Epigenetic modifications of tumor necrosis factor-alpha in joint cartilage tissue from osteoarthritis patients - CONSORT

Background:Osteoarthritis (OA) remains one of the most common osteopathy for centuries, which can be attributed to multiple risk factors including mechanical and biochemical ones. More and more studies verified that inflammatory cytokines play important roles in the progression of OA, such as tumor necrosis factor-alpha (TNF-α). In this study, we aimed to investigate the relationship between epigenetic manifestations of TNF-? and the pathogenesis of OA.Methods:Totally, 37 OA patients’ cartilage was collected through the knee joint and 13 samples of articular cartilage as healthy control was collected through traumatic amputation. Real-time PCR, Western blot and ELISA analysis were performed to observe the expression of target genes and proteins in collected samples.Results:Compared with the healthy control group, TNF-? was over-expressing in cartilage which was collected from OA patients. DNA hypomethylation, histone hyperacetylation and histone methylation were observed in the TNF-? promoter in OA compared with normal patients, and we also studied series of enzymes associated with epigenetics. The results showed that by increasing DNA methylation and decreasing histone acetylation in the TNF-? promoter, and TNF-? over-expression in OA cartilage was suppressed, histone methylation has no significant correlation with OA.Conclusion:In conclusion, the changes of epigenetic status regulate TNF-α expression in the cells, which are pivotal to the OA disease process. These results may give us a better understanding of OA and may provide new therapeutic options.     

Levalbuterol compared to racemic albuterol: efficacy and outcomes in patients hospitalized with COPD or asthma

STUDY OBJECTIVES: To compare clinical efficacy, patient outcomes, and medical costs in hospitalized patients treated with levalbuterol to those treated with racemic albuterol. DESIGN: Retrospective chart review. SETTING: A 180-bed community hospital. PATIENTS: Patients admitted to Halifax Regional Hospital with a diagnosis code for COPD or asthma from July 1 to December 31, 1998, and from July 1 to December 31, 1999, were eligible. In 1998, 125 patients were treated with nebulized racemic albuterol (2.5 mg q4h). In 1999, 109 patients were treated with levalbuterol (1.25 mg q8h). Measurements and results: Clinical efficacy was evaluated by the number of nebulizer treatments, improvement in symptoms and objective clinical findings, the length of hospital stay, and hospital discharge disposition. Medication and total hospital costs were calculated based on Red Book listings and Medicare reimbursement rates. Levalbuterol-treated patients required significantly fewer treatments with beta-agonists (mean [+/- SD] number of treatments, 19.0 +/- 12.7 vs 30.8 +/- 24.0; p < 0.001) and ipratropium bromide (mean number of treatments, 9.4 +/- 11.5 vs 23.2 +/- 25.1; p < 0.001) than did racemic albuterol-treated patients. The mean length of hospital stay in the levalbuterol group was almost 1 day less than that in the racemic albuterol group (4.7 +/- 2.9 vs 5.6 +/- 4.2 days, respectively; p < 0.058). Significantly more patients were readmitted to the hospital within 30 days in the racemic albuterol group compared with the levalbuterol group (16.4% vs 5.7%, respectively; p = 0.01). The mean total cost of nebulizer therapy was significantly greater for patients receiving racemic albuterol than for those receiving for levalbuterol ($112 +/- 101 vs $61 +/- 43, respectively; p < 0.001). The mean total hospital costs per patient were less for levalbuterol compared with racemic albuterol ($2756 +/- 2079 vs $3225 +/- 2714, respectively; p = 0.11). Regression analysis controlling for diagnosis, baseline FEV(1), and ipratropium use indicated that levalbuterol was associated with a length-of-stay savings of 0.91 days (p = 0.015), a total cost savings of $556 (p = 0.013), and a decrease in the likelihood of hospital readmission of 67% (p = 0.056). CONCLUSION: Compared with patients treated with racemic albuterol, those treated with levalbuterol required less medication, had shorter lengths of hospital stay, had decreased costs for nebulizer therapy and hospitalization, and appeared to have a more prolonged therapeutic benefit. These findings support using levalbuterol as first-line therapy for hospitalized adults with COPD or asthma.