Effect of recombinant erythropoietin on inflammatory markers in patients with affective disorders: A randomised controlled study

AimThis study investigated the effect of repeated infusions of recombinant human erythropoietin (EPO) on markers of inflammation in patients with affective disorders and whether any changes in inflammatory markers were associated with improvements on verbal memory.MethodsIn total, 83 patients were recruited: 40 currently depressed patients with treatment-resistant depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (sub-study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS) ⩽ 14) (sub-study 2). In both sub-studies, patients were randomised in a double-blind, parallel-group design to receive eight weekly intravenous infusions of EPO (Eprex; 40,000 IU/ml) or saline (0.9% NaCl). Plasma concentrations of interleukin 6 (IL-6), interleukin 18 (IL-18) and high sensitive c-reactive protein (hsCRP) were measured at week 1 (baseline) and weeks 5, 9 and 14. HDRS-17 and neuropsychological function was assessed at weeks 1, 9 and 14 using a test battery including the RAVLT Auditory Verbal Learning Test (primary depression and primary cognition outcomes in the original trial).ResultsEPO had no cumulative effect on plasma levels of IL-6 or IL-18 but increased hsCRP levels in patients with TRD (mean ± SD change in ng/L: EPO: 0.43 ± 1.64; Saline: −0.90 ± 2.43; F(1,39) = 4.78, p = 0.04). EPO had no effects on inflammatory markers in BD. There was no correlation between change in inflammatory markers and change in verbal memory.ConclusionsRepeated EPO infusions had no effect on IL-6 and IL-18 levels but produced a modest increase in hsCRP levels in patients with TRD. Changes over time in inflammatory markers were not correlated with changes in cognition suggesting that modulation of the inflammatory pathway is not a putative mechanism of the EPO-associated improvement of cognition in affective disorders.     

Successful treatment with famciclovir for varicella zoster virus infection resistant to acyclovir

Varicella zoster virus (VZV) reactivates more frequently in immunocompromised patients than immunocompetent subjects and is a significant cause of morbidity and mortality. Acyclovir is frequently used for treatment against VZV reactivation. However, long-term use of acyclovir can result in the emergence of VZV strain resistant to acyclovir.Here, we report a 67-year-old man with adult T-cell leukemia who suffered from herpes zoster with acyclovir-resistant VZV after long-term prophylaxis. The isolated viruses from his skin lesions were a mixture of acyclovir-resistant and acyclovir-susceptible strains. Sequence analysis showed the presence of thymidine kinase (TK) mutations in the resistant clones. Interestingly, oral administration of famciclovir, a prodrug form of penciclovir, resulted in resolution of his herpes zoster, although most acyclovir-resistant strains of VZV were reported to be resistant to penciclovir. This implied that a certain amount of susceptible VZV with wild-type viral TK gene was present in vivo, and that famciclovir could be phosphorylated intracellularly by the intact viral kinases. As famciclovir is more potent and longer-acting than acyclovir, the susceptible strains might have suppressed the generation and proliferation of the resistant in vivo. Even when VZV is developing resistance to acyclovir, famciclovir might be effective at least in the early resistant phase.     

成人隐匿性自身免疫糖尿病颈动脉内膜中膜厚度与谷氨酸脱羧酶抗体滴度的关系

目的探讨成人隐匿性自身免疫糖尿病(LADA)患者颈动脉内膜中膜厚度(C-IMT)与谷氨酸脱羧酶抗体(GADA)滴度的关系。方法选取2015年9月至2019年4月参与中南大学湘雅二医院国家代谢性疾病临床医学研究中心LADA临床试验研究的160名患者基线资料。以GADA滴度为界值分为高滴度LADA-1型(GADA滴度≥0.3)和低滴度LADA-2型(0.05≤GADA滴度0.3)。收集其颈动脉内膜中膜厚度资料及其他临床资料进行横断面分析。结果 LADA-2型患者年龄、高血压比例、代谢综合征比例、体质量、体质指数、腰围、臀围、收缩压、舒张压、空腹C肽、HOMA-IR、甘油三酯水平明显高于LADA-1型患者(P0.05),而胰岛素使用比例明显低于LADA-1型患者(P0.01)。与LADA-1型患者比较,LADA-2型患者C-IMT增厚者明显增多(P0.01),且C-IMT增厚更为显著(P0.001),在校正代谢综合征相关因素后差异仍显著。多元线性回归分析显示,C-IMT与饮酒史呈正相关(P0.01),与GADA滴度呈负相关(P0.01)。根据HOMA-IR将患者分为低HOMA-IR组(HOMA-IR≤2.0)和高HOMA-IR组(HOMA-IR2.0),LADA-1型高HOMA-IR组较低HOMA-IR组C-IMT显著升高(P0.01),而LADA-2型患者高、低HOMA-IR组无差异。结论 GADA低滴度的LADA患者较高滴度患者有更高的动脉粥样硬化风险,该风险与胰岛素抵抗相关。GADA滴度为LADA患者C-IMT增厚的独立影响因素。     

Resistencia a fármacos antituberculosos de primera línea en España durante 2010-2011. Estudio RETUBES

IntroductionThe magnitude of current resistance to antituberculosis drugs in Spain is unknown. The objective of this study is to describe resistance to first-line antituberculosis drugs and determine the associated factors.MethodsProspective multicenter study of adult tuberculosis patients with positive Mycobacterium tuberculosis culture and antibiogram including first-line drugs in 32 hospitals and one out-patient center of the Spanish Health System between 2010 and 2011.ResultsA total of 519 patients, 342 Spanish nationals and 177 (34.1%) foreigners were studied. Drug resistance was found in 48 (9.2%), of which 35 (6.7%) were isoniazid-resistant. There were 10 (1.9%) multiresistant cases and no strain was extremely resistant. Initial isoniazid resistance was detected in 28 of the 487 (5.7%) antituberulosis-naïve patients, most of whom were foreigners (P<.01). Acquired resistance was seen in 7 (22.6%) previously treated cases. Multiresistance was initial in 6 cases (1.2%) and acquired in another 4 (12.9%). Factors associated with initial isoniazid resistance were immigrant status and group cohabitation OR = 2.3; 95%CI: .98-5.67 and OR = 2.2; 95%CI: 1.05-7.07 respectively). The factor associated with acquired resistance to isoniazid was age below 50 years (P=.03).ConclusionsThe rate of initial isoniazid resistance is greater than estimated, probably due to the increase in immigration during recent years, suggesting that systematic national monitoring is required. Immigrants and those who cohabit in groups have a higher risk of isoniazid resistance.     

转录因子2基因单核苷酸多态性对瑞格列奈和罗格列酮疗效的影响

目的：研究转录因子2（TCF2）基因多态性与新诊断2型糖尿病患者服用瑞格列奈或罗格列酮疗效之间的相关性。方法选取新诊断的2型糖尿病患者209例并随机分配到瑞格列奈治疗组（104例）和罗格列酮治疗组（105例）,单药治疗48周,测量治疗前后人体基本参数及糖脂代谢相关指标,以及TCF2基因rs4430796变异。并分析不同基因型患者这2种药物的疗效有无差异。结果（1）209例患者中完成48周随访181例,其中AA、GA、GG基因型频率分别为50.2%,39.2%,10.6%。（2）罗格列酮治疗组,TCF2不同基因型患者在基线时的空腹胰岛素及胰岛β细胞功能指数有显著差异。（3）罗格列酮组不同基因型患者在治疗24及48周后精氨酸刺激试验一相胰岛素分泌反应存在显著差异。（4）经瑞格列奈治疗24周之后,不同基因型患者空腹胰岛素及胰岛素敏感性指数较基线时的改善存在显著差异。结论 TCF2基因rs4430796变异与罗格列酮及瑞格列奈治疗2型糖尿病的疗效相关。     

Human herpesvirus 6 (HHV-6) associated permanent hyponatremia in umbilical cord blood transplant recipient

Long-term neurocognitive deficits after human herpesvirus-6 (HHV-6) infection are common in stem-cell transplant recipients, but SIADH (Syndrome of inappropriate antidiuretic hormone secretion) with persistent hyponatremia is rare. A 51-year-old woman presented with somnolence, hyponatremia (121 mmol/L) and HHV-6 viremia (80,330 copies/ml) on day +22 post umbilical cord blood transplant (UCBT). With waterrestriction, tolvaptan and combination of foscarnet and ganciclovir, patient's hyponatremia and HHV-6 viremia improved. On day +94 UCBT, hyponatremia and HHV-6 viremia recurred. Foscarnet was restarted and continued until day +269 UCBT due to multiple HHV-6 recurrences with persistent hyponatremia. At day +712, patient remains on water-restriction, tolvaptan for continuous hyponatremia from SIADH.     

The role of vascular endothelial cells in tumor metastasis

Vascular endothelial cells (VECs) are an integral component of the inner lining of blood vessels, and their functions are essential for the proper functioning of the vascular system. The tight junctions formed by VECs act as a significant barrier to the intravasation and extravasation of tumor cells (TCs). In addition to that, the proliferation, activation, and migration of VECs play a vital role in the growth of new blood vessels, a process known as tumor angiogenesis, which is closely related to the malignant progression of tumors. However, during tumor progression, VECs undergo endothelial-to-mesenchymal transition (EndMT), which further promotes tumor progression. Furthermore, VECs act as the first line of defense against effector immune cells and help prevent immune cells from infiltrating into tumor tissues. VECs also secrete various cytokines that can contribute to regulating the stemness of tumor stem cells. Thus, it has been increasingly recognized that dysfunction of VECs is one of the key driving forces behind tumor metastasis, and therapeutic strategies targeting VECs have the potential to be an effective means of antitumor therapy. This review aims to present a comprehensive overview of the role and mechanisms of VECs in regulating tumor progression and metastasis, providing insights into the possibilities for the development of novel antitumor therapies that target VECs.     

Association between thyroid function and comorbid anxiety in first-episode and drug naïve patients with major depressive disorder

European Archives of Psychiatry and Clinical Neuroscience - Existing studies have shown that thyroid dysfunction is associated with depression. However, its role in major depressive disorder (MDD)...     

An eosinophil-Sos1-RAS axis licenses corticosteroid resistance in patients with allergic rhinitis

BackgroundCorticosteroid resistance (CR) is a serious disadvantage in treating many chronic inflammatory conditions. Eosinophils are the main inflammation cells in allergic reactions. Environmental pollution, such as PM2.5, is associated with the pathogenesis of allergic disorders. The objective of this study is to elucidate the mechanism by which the exposure to PM2.5 confers eosinophil CR status.MethodsPatients with allergic rhinitis were recruited and assigned to corticosteroid sensitive (CS) and CR groups. Eosinophils were purified from nasal lavage fluids collected from patients with allergic rhinitis. A murine AR mouse model was developed with dust mite allergens and PM2.5 as the sensitization reagents.ResultsCR status was detected in about 60% eosinophil collected in patients with AR. Upon exposure to eosinophil activators, CS eosinophils released a large quantity of mediators, which was suppressed by the presence of steroids in the culture. CR eosinophils demonstrated resistance to steroidal therapy. RAS activation levels in eosinophils were higher in CR eosinophils than in CS eosinophils. Higher expression of the Son of sevenless-1 (Sos1) was detected in CR eosinophils, which formed a complex with RAS and glucocorticoid receptor-α in CR eosinophils to prevent the binding between steroids and glucocorticoid receptor-α. The presence of an Sos1 inhibitor dissociated glucocorticoid receptor-α from RAS/Sos1 complex, that restored the sensitivity to steroids in eosinophils. Administering the Sos1 inhibitor effectively attenuated the experimental allergic rhinitis.ConclusionsCR status was detected in approximately 1/3 eosinophils sampled from patients with allergic rhinitis. Sos1 was instrumental in the development and perseverance of CR in eosinophils. Sos1 inhibition restored sensitivity to steroids in CR eosinophils, which effectively reduced experimental allergic rhinitis.     

Neisseria meningitidis serogroup W135 in a traveler visiting Japan from Argentina, 2019

Invasive meningococcal disease (IMD) can occur in travelers returning from mass-gathering events or endemic regions. We present a 60-year-old Argentine traveler to Tokyo who developed IMD by Neisseria meningitidis Serogroup W135 during her stay in Japan. N. meningitidis serogroup W135 infection has become common in Argentina, whereas IMD less commonly occurs in Japan. Considering the prevalence, the patient most likely acquired the infection in Argentina, and it developed in Japan. Air travel enables passengers to reach the four corners of the world within a few days. IMD should be considered in travelers due to its potential to induce rapid clinical deterioration and transmission.