BACKGROUNDThere has been an increase in cases of inflammatory bowel disease (IBD) in recent years. There is also greater access and availability of immunosuppressive and biological agents, which increase the risk of opportunistic infection despite improving the quality of life and promoting mucosal healing. Tuberculosis (TB) remains a public health problem, and it has a high incidence in several countries. Therefore, knowledge of the risk of developing TB in patients with IBD is important.AIMTo evaluate the risk of active TB in patients with IBD under treatment from an endemic area in Latin America.METHODSA standard questionnaire included demographic variables, clinical aspects of IBD disease, history of active TB during treatment, active TB characteristics and evolution, initial screening and results and time from the start of anti-tumor necrosis factor alpha (TNFα) to TB development.RESULTSAzathioprine, anti-TNFα and the combination of these two drugs were associated with a higher risk of active TB incidence. The TNFα blockers increased the relative risk of developing active TB compared to other treatments. All four multivariable models showed that the use of TNFα blockers alone or in combination with azathioprine was an important risk factor for the incidence of active TB. After adjustment for sex, age, type of IBD and latent TB, anti-TNFα with azathioprine increased the relative risk to 17.8 times more than conventional treatment. Late TB, which was diagnosed 3 mo after the start of anti-TNFα, was the most frequent.CONCLUSIONTreatment with anti-TNFα increased the risk of active TB in IBD patients from an endemic area in Latin America. This risk was increased when anti-TNFα was combined with azathioprine. The time from the beginning of the treatment to the active TB diagnosis suggests a new TB infection. 相似文献
AIM:To examine surgical and medical outcomes for patients with cholangiocarcinoma using a populationbased cancer registry.METHODS:Using the California Cancer Registry’s Cancer Surveillance Program,patients with intrahepatic cholangiocarcinoma treated in Los Angeles County from 1988 to 2006 were identified and evaluated for clinical and pathologic factors and therapies received(surgery,radiation,and chemotherapy).The surgical cohort was further categorized into three treatment groups:patients who received adjuvant chemotherapy,adjuvant chemoradiation,or underwent surgery alone(no chemotherapy or radiation administered).Survival was assessed by Kaplan-Meier method;and Cox proportional hazard modeling was used in multivariate analysis.RESULTS:Of 825 patients,60.2% received no treatment.Of the remaining 328 patients,18.5% chemotherapy only,7.4% chemoradiation,and 13.8% underwent surgery.More male patients underwent surgical resection(P = 0.004).Surgical patients were younger than the patients receiving chemotherapy or chemoradiation(P < 0.001).Of the surgical cohort(n = 114),60.5% underwent surgery alone while 39.5% underwent surgery plus adjuvant therapy(chemotherapy n = 20;chemoradiation,n = 21)(P < 0.001).Median survival for all patients in the study was 6.6 mo.Median survival was highest for patients who underwent surgery(23 mo),whereas both chemotherapy(9 mo) and chemoradiation(8 mo) alone were each less effective(P < 0.001).By multivariate analysis,extent of disease,receipt of surgery,and administration of chemotherapy(with/without surgery) were independent predictors of overall survival.CONCLUSION:This study demonstrates that surgery is a critical treatment modality.Multimodality treatment has yet to be standardized,but play a role in optimal therapy for cholangiocarcinoma. 相似文献
Dynamic Intraligamentary Stabilization (DIS) is a technique for preservation, anatomical repair and stabilization of a freshly injured anterior cruciate ligament (ACL). The main purpose of this study was to evaluate the short-term re-operation rate when compared to traditional autograft reconstruction.
Methods
Four, from the developer independent, centres enrolled patients that underwent ACL repair by DIS, according to the specific indications given by MRI imaging at a minimum follow-up of 12 months. The re-operation rate was recorded as primary outcome. Secondary outcome measures were the postoperative antero-posterior knee laxity (using a portable Rolimeter®), as well as the Tegner, Lysholm and IKDC Scores.
Results
A total of 105 patients were investigated with a median follow-up of 21 months. Thirteen patients were lost to follow-up. Of the remaining 92 patients 15 (16.3%) had insufficient functional stability and required subsequent ACL reconstruction. These patients were excluded from further analysis, leaving 77 consecutive patients for a 12 months follow-up. The median age at time of surgery was 30 years for that group. At time of follow-up a median antero-posterior translation difference of 2 mm was measured. None of these patients reported subjective insufficiency (giving way), but in 14 patients (18.2%), the difference of antero-posterior translation was more than 3 mm. We found a median Tegner Score of 5.5, a median Lysholm Score of 95.0 and a median IKDC Score of 89.4.
Conclusion
The main finding of this multicentre study is a relevant re-operation rate of 16.3%. Another 18.2% showed objective antero-posterior laxity (≥ 3 mm) during testing raising the suspicion of postoperative non-healing. The failure rate of DIS in this study is higher than for reconstruction with an autologous tendon graft. However, our successfully treated patients had a good clinical and functional outcome based on antero-posterior knee laxity and clinical scores, comparable to patients treated by autograft reconstruction.
The vascular endothelium is specifically sensitive to oxidative stress, and this is one of the mechanisms that causes widespread endothelial dysfunction in most cardiovascular diseases and disorders. Protection against reactive oxygen species (ROS)-mediated oxidative damage via antioxidant mechanisms is essential for tissue maintenance and shows therapeutic potential for patients suffering from cardiovascular and metabolic disorders. Salvianolic acid B (SalB), a natural bioactive component known from Traditional Chinese Medicine, has been reported to exert cellular protection in various types of cells. However, the underlying mechanisms involved are not fully understood. Here, we showed that SalB significantly promoted the migratory and tube formation abilities of human bone marrow derived-endothelial progenitor cells (BM-EPCs) in vitro, and substantially abrogated hydrogen peroxide (H2O2)-induced cell damage. SalB down-regulated Nox4 and eNOS, as well as nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase expression upon H2O2 induction that in turn prevents oxidative-induced endothelial dysfunction. Moreover, SalB suppressed the Bax/Bcl-xL ratio and caspase-3 activation after H2O2 induction. Furthermore, our results provide mechanistic evidence that activation of the mTOR/p70S6K/4EBP1 pathways is required for both SalB-mediated angiogenic and protective effects against oxidative stress-induced cell injury in BM-EPCs. Suppression of MKK3/6-p38 MAPK-ATF2 and ERK1/2 signaling pathways by SalB significantly protected BM-EPCs against cell injury caused by oxidative stress via reduction of intracellular ROS levels and apoptosis. Taken together, by providing a mechanistic insight into the modulation of redox states in BM-EPCs by SalB, we suggest that SalB has a strong potential of being a new proangiogenic and cytoprotective therapeutic agent with applications in the field of endothelial injury-mediated vascular diseases. 相似文献
With the increase of age, increased susceptibility to apoptosis and senescence may contribute to proliferative and functional impairment of endothelial progenitor cells (EPCs). The aim of this study was to investigate whether salidroside (SAL) can induce angiogenic differentiation and inhibit oxidative stress-induced apoptosis in bone marrow-derived EPCs (BM-EPCs), and if so, through what mechanism.
Experimental Approach
BM-EPCs were isolated and treated with different concentrations of SAL for up to 4 days. Cell proliferation, migration and tube formation ability were detected by DNA content quantification, transwell assay and Matrigel-based angiogenesis assay. Gene and protein expression were assessed by qRT-PCR and Western blot respectively.
Key Results
Treatment with SAL promoted cellular proliferation and angiogenic differentiation of BM-EPCs, and increased VEGF and NO secretion, which in turn mediated the enhanced angiogenic differentiation of BM-EPCs. Furthermore, SAL significantly attenuated hydrogen peroxide (H2O2)-induced cell apoptosis, reduced the intracellular level of reactive oxygen species and restored the mitochondrial membrane potential of BM-EPCs. Moreover, SAL stimulated the phosphorylation of Akt, mammalian target of rapamycin and p70 S6 kinase, as well as ERK1/2, which is associated with cell migration and capillary tube formation. Additionally, SAL reversed the phosphorylation of JNK and p38 MAPK induced by H2O2 and suppressed the changes in the Bax/Bcl-xL ratio observed after stimulation with H2O2.
Conclusions and Implications
These findings identify novel mechanisms that regulate EPC function and suggest that SAL has therapeutic potential as a new agent to enhance vasculogenesis as well as protect against oxidative endothelial injury. 相似文献
We used in vitro DNA amplification by the polymerase chain reaction and nonradioactive probes for prenatal diagnosis of beta thalassemia in Chinese from the Guangdong province. Exact molecular diagnoses were made in all 20 fetuses studied over a 6-month period. We conclude that this method of prenatal diagnosis for beta thalassemia is a viable approach in many parts of the world where this disease is common. 相似文献