Independent prognostic value of the congestion and renal index in patients with acute heart failure.

BACKGROUND: Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF. METHODS: We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes. RESULTS: A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system. CONCLUSIONS: In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.

Imaging characteristics of a rare case of monostotic fibrous dysplasia of the sacrum: A case report.

BACKGROUND: Fibrous dysplasia (FD) is a common benign intramedullary fibro-osseous lesion. Involvement of the spine is rare, with the literature including only case reports, and cases of monostotic FD (MFD) in the sacrum are extremely rare. A correct preoperative diagnosis of spinal MFD is important for clinicians to select proper treatment. CASE SUMMARY: We retrospectively assessed a case report of MFD in the sacrum. This patient was examined by computed tomography (CT) and magnetic resonance imaging (MRI), and the diagnosis was confirmed by pathology. A review of the literature was performed to analyze the imaging characteristics and differential diagnoses of spinal MFD. For our patient, the CT scan showed the lesion to be expansile, with ground glass opacity and a sclerotic rim. On MRI, the lesion showed iso-low signal intensity on T1WI and iso-high signal intensity on T2WI. A low signal rim was found on T1WI and T2WI. Our patient was treated by posterior focal excision, decompression, bone grafting, fusion and pedicle screw fixation. A satisfactory result was achieved, with pain disappearance. No complications had occurred at the 1-year follow up. CONCLUSION: MFD is an expansile osteolytic change. Ground glass opacity and a sclerotic margin are obvious characteristics. The lesion often involves the vertebral body and posterior element. Knowledge of these imaging characteristics of spinal FD could be helpful for diagnosis and prevent unnecessary procedures.

[Research Advances of Monocyte/Macrophage in Chronic Lymphocytic Leukemia--Review].

Chronic lymphocytic leukemia（CLL）is a malignant hematologic disease with heterogeneous clinical course, about two thirds of patients exhibit a long survival, but the remaining third of patients show aggressiveness of disease or poor response to conventional treatment even drug resistance. Studies suggested that tumor microenvironment possesses a critical effect in CLL disease progression in recent years. Monocyte/macrophage, as an important componens of tumor microenvironment, play a promotive role in the growth and drug reistance of tumor cells by direct cell-to-cell contact, secreting cytokines and suppressing antitumor responses. Therefore, exploring the monocyte/macrophage in CLL can provide theoretic basis for target treatment of CLL. In this review, the function of monocyte/macrophage and recent advances in therapy of CLL are discussed.

The proportion of peripheral regulatory T cells in patients with Multiple Sclerosis: A meta-analysis.

BACKGROUND: Accumulating evidence indicates that regulatory T cells (Tregs) play an important role in the maintenance of immune tolerance. And dysfunction or deficiency of Tregs is thought to be involved in the pathogenesis of Multiple Sclerosis (MS). Nevertheless, previous studies reporting Tregs in patients were controversial due to the different markers adopted to identify Tregs. To clarify the status of Tregs in the pathogenesis of MS patients, we did a meta-analysis of the results published previously to assess the proportion of Tregs in peripheral blood (PB) in patients with MS. METHODS: We systematically searched Embase, PubMed, Cochrane, Web of Knowledge, FDA.gov, and Clinical Trials.gov for the studies reporting the proportion of Tregs in MS patients. Our main endpoints were the proportion of Tregs among CD4+ T cells in PB defined by different markers. We assessed pooled data by using a random-effects model. Our meta-analysis had been registered at International Prospective Register of Systematic Reviews (PROSPERO) (number CRD42017064906). RESULTS: Of 885 identified studies, a total 16 studies were selected in our analysis. There was no significant difference between MS patients and control subjects in Tregs identified by all Tregs definition methods [-0.07, (-0.46, 0.31, p = 0.706)] and Tregs defined by "CD4+ CD25+" [0.24, (-0.18, 0.65), p = 0.263]. Compared with control subjects, MS patients had a lower proportion of Tregs defined by "CD4+ CD25+ FOXP3+" [-0.75, (-0.46,0.31), p = 0.001]. CONCLUSION: Under random effect model of meta-analysis, the data showed that the results of Tregs in MS were different according to the definition method; and the proportion of Tregs defined by "CD4+ CD25+ FOXP3+" was decreased in MS. That result demonstrates that FOXP3 may be a vital definition of Tregs, and Tregs defined by stricter definition methods should be involved in the pathogenic mechanisms of MS.

Cetuximab for esophageal cancer: an updated meta-analysis of randomized controlled trials.

BACKGROUND: Increasing evidence indicates that cetuximab (CET) combined with chemoradiotherapy may be effective for patients with esophageal cancer. However, the recent results are still contradictory and no consensus has yet been reached on this issue. To evaluate the clinical effects and safety of CET, we conducted an updated meta-analysis by retrieving published data up to June 2018. METHODS: A comprehensive literature search was performed in several electronic databases, including PubMed, Embase, the Cochrane Library, CNKI database and Chinese Biomedicine Database using subject terms and free terms. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to determine the efficiency and safety of CET. RESULTS: This meta-analysis included 10 randomized controlled trials (RCTs). Five RCTs reported localized esophageal cancer and other five RCTs reported metastatic esophageal cancer. For these patients with localized esophageal cancer, CET could not significantly improve the response rate, overall survival and progression-free survival (PFS, 1-5 years). But CET treatment might increase the incidences of diarrhea (OR = 2.07; CI = 1.01-4.25) and rash (OR = 16.91; CI = 3.20-89.42). For other patients with metastatic esophageal cancer, the addition of CET significantly increased the response rate (OR = 3.34; CI = 1.90-5.88), disease control rate (OR = 2.92; CI = 1.49-5.71) and 2-year overall survival (OR = 2.78; CI = 1.20-6.46) compared with the control group. However, CET could not improve the 1-year overall survival and might make patients with metastatic esophageal cancer more susceptible to rash (OR = 5.50; CI = 2.14-14.14). No significant differences in other adverse effects were found between the two groups. CONCLUSIONS: Our findings suggested that adding CET to multimodal therapy significantly improved response rate and disease control rate for patients with metastatic esophageal cancer rather than patients with localized esophageal cancer. CET might be a safe therapeutic choice, but CET failed to significantly improve the overall survival and PFS for patients with localized or metastatic esophageal cancer.

The Proportion of Regulatory T Cells in Patients with Systemic Lupus Erythematosus: A Meta-Analysis.

BACKGROUND: Accumulating evidence indicates that a deficiency in or dysfunction of regulatory T cells (Tregs) is involved in the pathogenesis of systemic lupus erythematosus (SLE). As different markers have been used to identify Tregs, recent studies on the proportions of Tregs in SLE patients have generated controversial results. To clarify the status of Tregs in such patients, we determined the proportions of Tregs present during development of the disease, with special consideration of controversial cellular markers. METHODS: We identified studies reporting the proportions of Tregs in SLE patients by searching relevant databases through March 2018. Using the PRISMA guidelines, we performed a random effects meta-analysis of the frequencies of Tregs defined in different ways. Inconsistency was evaluated using the I-squared index (I2), and publication bias was assessed by examining funnel plot asymmetry using the Begger and Egger tests. RESULTS: Forty-four studies involving 2779 participants were included in the meta-analysis. No significant difference in the proportions of Tregs was evident between 1772 patients and 1007 controls [-0.191, (-0.552, 0.362), p = 0.613, I2 = 95.7%]. We next conducted subanalyses based on individual definitions of Tregs. When the Treg definition included "FOXP3-positive" cells, the proportions did not differ between SLE patients and controls [-0.042, (-0.548, 0.632), p = 0.889, I2 = 96.6%]; this was the case when Tregs were defined as either "CD25low/-FOXP3+" or "CD25high/+FOXP3+" cells. SLE patients had lower proportions of Tregs that were "single CD25-positive" [-1.428, (-1.982, -0.873), p < 0.001, I2 = 93.4%] and "CD127-negative" [-1.093, (-2.002, -0.183), p = 0.018, I2 = 92.6%] compared to controls. Tregs defined as "CD25bright," "CD25bright/highCD127low/-," and "CD25highCD127low/-FOXP3+" did not differ in proportion between SLE patients and controls. CONCLUSIONS: The Treg proportions varied by the cellular identification method used. The proportions of Tregs that were accurately identified and functionally validated fell among patients with SLE. Stricter definitions of Tregs are necessary when evaluating the status of such patients.

Levels of peripheral Th17 cells and serum Th17-related cytokines in patients with multiple sclerosis: A meta-analysis.

BACKGROUND: Multiple reports have described the proportion of Th17 cells in peripheral blood and serum levels of Th17-related cytokines in patients with multiple sclerosis (MS). To clarify the status of Th17 cells and Th17-related cytokines in MS patients, we did a meta-analysis of the results published previously to assess the levels of peripheral Th17 cells and serum Th17-related cytokines in patients with MS. METHODS: We searched Embase, PubMed, Cochrane, Web of Knowledge, FDA.gov, and Clinical Trials.gov systematically for studies reporting the proportion of Th17 cells and the serum levels of Th17-related cytokines (IL-17, IL23) in MS patients. Our main endpoints were the proportion of Th17 cells among CD4+ T cells in peripheral blood (PB), serum IL-17 levels, and serum IL-23 levels. We assessed pooled data by using a random-effects model. It has been registered at International Prospective Register of Systematic Reviews (PROSPERO) (number CRD42017059113). RESULTS: Of 560 identified studies, a total of 12 studies were selected in our analysis. Compared with control subjects, MS patients had a higher proportion of Th17 cells [1.37, (0.53, 2.21)] in PB, an elevated levels of serum IL-17 [2.48, (1.25, 3.71)] and an increased IL-23 levels in serum [2.29, (0.58, 4.00)]. CONCLUSION: Under random effect model of meta-analysis, the data showed that the proportion of Th17 cells in PB and levels of serum IL-17 and IL-23 increased among MS patients compared to control subjects. This result demonstrated that Th17 cells and Th17-related cytokines may be involved in the pathogenic mechanisms of MS.

Posterior C1-C2 screw-rod fixation and autograft fusion for the treatment of os odontoideum with C1-C2 instability.

OBJECTIVE: To report our experience treating os odontoideum with C1-C2 instability via C1-C2 screw-rod fixation and autograft fusion and to explore the clinical efficacy of such a treatment strategy. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients who were diagnosed with os odontoideum with C1-C2 instability and treated by posterior C1-C2 screw-rod fixation and fusion. Neurological deficits were measured with the Japanese Orthopedic Association (JOA) scoring system and neck pain was assessed using the Visual Analogue Scale (VAS) score. Fusion was determined based on the presence of bridging bone in computed tomography (CT) imaging, whereas stability was determined based on the lack of movement in dynamic radiographs. RESULTS: Thirty-two patients (18 males) were included in the study. The surgery was successfully accomplished in all patients. Thirty (93.8%) patients had confirmed C1-C2 bony fusion in CT images and all patients (100%) were stable in dynamic radiographs. The mean preoperative JOA score was 14.3±1.4 (range 11-16); at the final visit, it increased to 16.2±0.8 (range 14-17) (p<0.001). The mean preoperative VAS score was 3.8±0.7 (range 3-5) and decreased at the final visit to 1.0±0.6 (range 0-2) (p<0.001). CONCLUSION: Our treatment strategy (C1-C2 screw-rod fixation and autograft fusion) can achieve excellent clinical results with minor complications for patients with os odontoideum with C1-C2 instability.

Efficacy and safety of combination therapy of chemoembolization and radiofrequency ablation with different time intervals for hepatocellular carcinoma patients.

BACKGROUND AND OBJECTIVES: Combination of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) has become an effective alternative therapy for hepatocellular carcinoma (HCC). In clinical practice, the choice of time interval between TACE and RFA is a key point for curative effect, but optimal time interval is uncertain in guidelines. We aim to explore the optimal time interval for HCC patients of Child-Pugh classification A or B. METHODS: Two hundred and thirty-three HCC patients of Child A or B who had undergone TACE and RFA were enrolled and divided into seven groups according to different time intervals (1-7weeks). Tumor damage, liver function, complications and survival time of patients after treatment were analyzed. RESULTS: Complete remission rate and total effective rate decreased in groups with the prolonged time interval (p < 0.05). Average Child-Pugh score of patients in first three groups significantly increased one month after combination treatment (p < 0.01). While that not happened in other groups. Complications occurred in 16.7% patients, similarly occurred in groups (p > 0.1). Median survival time in groups four and five were 42 months, longer than other groups (p < 0.01). CONCLUSION: A period of 3-5 weeks is the optimal time interval between TACE and RFA for HCC patients of Child-Pugh classification A or B.

GLP-1 analogue CJC-1131 prevents amyloid ß protein-induced impirments of spatial memory and synaptic plasticity in rats.

Although amyloid ß protein (Aß) has been recognized as one of the main pathological characteristics in the brain of Alzheimer's disease (AD), the effective strategies against Aß neurotoxicity are still deficient up to now. Glucagon-like peptide 1 (GLP-1), a natural gut hormone, was found to be effective in modulating insulin signaling and neural protection, but short half-life limited its clinical application in AD treatment. CJC-1131, a newly designed GLP-1 analogue with very longer half-life, has shown good effectiveness in the treatment of type 2 diabetes mellitus (T2DM). However, it is unclear whether CJC-1131 could alleviate Aß-induced neurotoxicity in cognitive behavior and electrophysiological property. The present study investigated the effects of CJC-1131 on the Aß-induced impairments in spatial memory and synaptic plasticity of rats by using Morris water maze test and in vivo field potential recording. The results showed that Aß1-42-induced increase in the escape latency of rats in hidden platform test and decrease in swimming time percent in target quadrant were effectively reversed by CJC-1131 pretreatment. Further, CJC-1131 prevented against Aß1-42-induced suppression of hippocampal long term potentiation (LTP). In addition, Aß1-42 injection resulted in a significant decrease of p-PKA in the hippocampus, which was effectively prevented by CJC-1131 treatment. These results indicated that CJC-1131 protected the cognitive function and synaptic plasticity of rats against Aß-induced impairments, suggesting that GLP-1 analogue CJC-1131 might be potentially beneficial to the prevention and treatment of AD, especially those with T2DM or blood glucose abnormality.

A novel dimeric thymosin beta 4 with enhanced activities accelerates the rate of wound healing.

OBJECTIVE: Thymosin beta 4 (Tß4) is a peptide with 43 amino acids that is critical for repair and remodeling tissues on the skin, eye, heart, and neural system following injury. To fully realize its utility as a treatment for disease caused by injury, the authors constructed a cost-effective novel Tß4 dimer and demonstrated that it was better able to accelerate tissue repair than native Tß4. METHODS: A prokaryotic vector harboring two complete Tß4 genes with a short linker was constructed and expressed in Escherichia coli. A pilot-scale fermentation (10 L) was performed to produce engineered bacteria and the Tß4 dimer was purified by one-step hydrophobic interaction chromatography. The activities of the Tß4 dimer to promote endothelial cell proliferation, migration, and sprouting were assessed by tetramethylbenzidine (methylthiazol tetrazolium), trans-well, scratch, and tube formation assays. The ability to accelerate dermal healing was assessed on rats. RESULTS: After fermentation, the Tß4 dimer accounted for about 30% of all the bacteria proteins. The purity of the Tß4 dimer reached 98% after hydrophobic interaction chromatography purification. An average of 562.4 mg/L Tß4 dimer was acquired using a 10 L fermenter. In each assay, the dimeric Tß4 exhibited enhanced activities compared with native Tß4. Notably, the ability of the dimeric Tß4 to promote cell migration was almost two times higher than that of Tß4. The rate of dermal healing in the dimeric Tß4-treated rats was approximately 1 day faster than with native Tß4-treated rats. CONCLUSION: The dimeric Tß4 exhibited enhanced activity on wound healing than native Tß4, and the purification process was simple and cost-effective. This data could be of significant benefit for the high pain and morbidity associated with chronic wounds disease. A better strategy to develop Tß4 as a treatment for other diseases caused by injuries such as heart attack, neurotrophic keratitis, and multiple sclerosis was also described.