Debate on MERS-CoV respiratory precautions: surgical mask or N95 respirators?

Since the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in mid-2012, there has been controversy over the respiratory precaution recommendations in different guidelines from various international bodies. Our understanding of MERS-CoV is still evolving. Current recommendations on infection control practices are heavily influenced by the lessons learnt from severe acute respiratory syndrome. A debate on respiratory precautions for MERS-CoV was organised by Infection Control Association (Singapore) and the Society of Infectious Disease (Singapore). We herein discuss and present the evidence for surgical masks for the protection of healthcare workers from MERS-CoV.     

Exosomes play roles in sequential processes of tumor metastasis

Overwhelming evidence demonstrates that exosomes, a series of biologically functional small vesicles of endocytic origin carrying a variety of active constituents, especially tumor-derived exosomes, contribute to tumor progression and metastasis. This review focuses on the specific multifaceted roles of exosomes in affecting sequenced four crucial processes of metastasis, through which cancer cells spread from primary to secondary organs and finally form macroscopic metastatic lesions. First, exosomes modulate the primary tumor sites to assist cancer growth and dissemination. In this part, five main biological events are reviewed, including the transfer of oncogenic constituents, the recruitment and activation of fibroblasts, the induction of angiogenesis, immunosuppression and epithelial-mesenchymal transition (EMT) promotion. In Step 2, we list two recently disclosed mechanisms during the organ-specific homing process: the exosomal integrin model and exosomal epidermal growth factor receptor (EGFR)/miR-26/hepatocyte growth factor (HGF) model. Subsequently, Step 3 focuses on the interactions between exosomes and pre-metastatic niche, in which we highlight the specific functions of exosomes in angiogenesis, lymphangiogenesis, immune modulation and metabolic, epigenetic and stromal reprogramming of pre-metastatic niche. Finally, we summarize the mechanisms of exosomes in helping the metastatic circulating tumor cells escape from immunologic surveillance, survive in the blood circulation and proliferate in host organs.     

Eficacia de leflunomida 100 mg semanales comparado con dosis bajas de metotrexate en pacientes con artritis reumatoide activa. Estudio clínico doble ciego aleatorizado

ObjectiveTo determine the clinical efficacy and safety of Leflunomide (LFN) 100 mg/week compared to low dose Methotrexate (MTX) 10 mg/week in a double-blind, randomized, controlled trial with 52 weeks of follow up in Rheumatoid Arthritis (RA) patients.Patients and methodsPatients who met ARC1987 criteria for RA were included. All patients had medical records, including laboratory tests and hand X-rays. Clinical evaluations for improvement and ACR and EULAR response criteria were performed. Statistical analysis for independent's samples between both groups defined a P value of ≤ .05. Safety was evaluated by comparing the proportion of adverse events (AE) registered.ResultsOf 90 patients screened; five were withdrawn; the remaining 85 patients were randomised: 43 LFN and 42 MTX. Sixty-three patients completed the study; 72% in the LFN group and 74.4% in the MTX group. ACR20 improvement criteria were achieved by LFN group in 90.3%, and in MTX 78.1% (P = .14) at week 52. EULAR improvement criteria applied at the end point showed a DAS28 score for the LFN group of 3.45, and for the MTX group was 3.67(P = .43). Total withdrawals, including loss during follow up, AE and lack of efficacy for each group was 12 patients in the LFN group, and 10 patients in the MTX group. Regarding safety, no serious AE of a life threatening nature were reported.ConclusionsThese outcomes confirm that LFN 100 mg/week offers an adequate and sustained improvement effect on the clinical manifestations of RA, similar to low dose treatment with MTX 10 mg/every week after 52 weeks of follow up; it may be a good therapeutic option alone or in combination with others anti-rheumatic drugs.     

History of myocardial iron loading is a strong risk factor for diabetes mellitus and hypogonadism in adults with β thalassemia major

Endocrinopathies are common complications of transfusional hemosiderosis among patients with β thalassemia major (TM). Previous studies had shown associations between some endocrinopathies and iron overload of the myocardium, liver and/or endocrine organs as assessed by MRI techniques. This retrospective analysis of 92 patients with TM (median age 36 yr) from a tertiary adult thalassemia unit in UK aimed to determine independent risk factors associated with endocrinopathies among these patients. Unlike previous studies, longitudinal data on routine measurements of iron load [worst myocardial and liver T2* values since 1999, worst LIC by MRI‐R2 since 2008 and average 10‐yr serum ferritin (SF)] up to April 2010 together with demographic features and age of initiating chelation were analyzed for associations with endocrinopathies. The most common endocrinopathies in this cohort were hypogonadism (67%) and diabetes mellitus (DM) (41%), and these were independently associated with myocardial T2* <20 ms (P < 0.001 and P = 0.008, respectively) and increased age (P = 0.002 and P = 0.016, respectively). DM and hypogonadism were independently associated with average SF >1250 μg/L (P = 0.003) and >2000 μg/L (P = 0.047), respectively. DM was also associated with initial detection of abnormal myocardial T2* at an older age (30 yr vs. 24 yr, P = 0.039). An abnormal myocardial T2* may therefore portend the development of DM and hypogonadism in patients with TM.     

Decreased expression of phospholipase C-beta 2 isozyme in human platelets with impaired function

Platelets from a patient with a mild inherited bleeding disorder and abnormal platelet aggregation and secretion show reduced generation of inositol 1,4,5-trisphosphate, mobilization of intracellular Ca2+, and phosphorylation of pleckstrin in response to several G protein mediated agonists, suggesting a possible defect at the level of phospholipase C (PLC) activation (see accompanying report). A procedure was developed that allows quantitation of platelet PLC isozymes. After fractionation of platelet extracts by high-performance liquid chromatography, 7 out of 10 known PLC isoforms were detected by immunoblot analysis. The amount of these isoforms in normal platelets decreased in the order PLC- gamma 2 > PLC-beta 2 > PLC-beta 3 > PLC-beta 1 > PLC-gamma 1 > PLC- delta 1 > PLC-beta 4. Compared with normal platelets, platelets from the patient contained approximately one-third the amount of PLC-beta 2, whereas PLC-beta 4 was increased threefold. These results suggest that the impaired platelet function in the patient in response to multiple G protein mediated agonists is attributable to a deficiency of PLC-beta 2. They document for the first time a specific PLC isozyme deficiency in human platelets and provide an unique opportunity to understand the role of different PLC isozymes in normal platelet function.     

乳腺浸润性微乳头状癌(IMPC) 29例临床分析

 目的  研究乳腺浸润性微乳头状癌(invasive micropapillary carcinoma of the breast,IMPC)的临床病理特征以及生存预后分析。方法  选择2006年6月至2013年6月在本院收治的IMPC 29例,中位随访42个月,分析其临床病理特点、局部复发率、远处转移率及总生存率(overall survival,OS)等生存预后指标;与320例浸润性导管癌(invasive ductal carcinoma,IDC)病例进行对照,分析比较两组间的临床病理特点及生存预后指标。为进一步探讨IMPC病理类型对于生存预后的影响,将58例IDC与29例IMPC进行2∶1配对对照研究,分析比较两组间的生存预后指标。结果   29例IMPC中23例(79.3%)发生淋巴结转移,其中4枚及以上淋巴结转移的有15例(51.7%),18例(62.1%)伴有脉管侵犯。分子分型以Luminal B型为主(21例)。3年无局部复发生存率(local recurrence free survival,LRFS)、无转移生存率(metastasis free survival,MFS)、OS分别为:74%、86%、90%。Cox回归分析得出淋巴结转移个数是IMPC局部复发的影响因素(P=0.048)。与IDC组比较,IMPC组肿瘤体积大(3.70 cm vs.2.81 cm,P=0.007),淋巴结转移率高(79.3% vs.45.0%,P<0.001),淋巴结转移个数多(5.90 vs.2.16,P=0.003),淋巴结分级高分级比例较高(N2:24.1% vs.7.5%,N3:27.6% vs.6.9%,P<0.001),脉管侵犯率高(62.1% vs.20.0%,P<0.001),手术方式中标准根治术比例高(24.2% vs.3.1%,P<0.001),化疗方式中新辅助化疗比例高(31.0% vs.9.1%,P<0.001),其余方面差异无统计学意义。Log Rank检验生存分析得出IMPC组的LRFS显著低于IDC组(P=0.001),但两组间的MFS及OS差异无统计学意义(P=0.074及0.106)。将58例IDC与29例IMPC进行配对对照研究,Log Rank检验生存分析得出两组间的LFRS、MFS与OS差异均无统计学意义(P=0.586、0.965、0.920)。 结论   乳腺IMPC是一类预后较差的特殊类型乳腺癌,其较高的淋巴脉管侵犯性而非这一病理类型,与肿瘤的生存预后相关。