Aim
The aim of this study was to identify factors predictive of serious infections over time in patients with systemic lupus erythematosus (SLE).
Methods
A multi-ethnic, multi-national Latin American ...SLE cohort was studied. Serious infection was defined as one that required hospitalization, occurred during a hospitalization or led to death. Potential predictors included were sociodemographic factors, clinical manifestations (per organ involved, lymphopenia and leukopenia, independently) and previous infections at baseline. Disease activity (SLEDAI), damage (SLICC/ACR Damage Index), non-serious infections, glucocorticoids, antimalarials (users and non-users), and immunosuppressive drugs use; the last six variables were examined as time-dependent covariates. Cox regression models were used to evaluate the predictors of serious infections using a backward elimination procedure. Univariable and multivariable analyses were performed.
Results
Of the 1243 patients included, 1116 (89.8%) were female. The median (interquartile range) age at diagnosis and follow-up time were 27 (20–37) years and 47.8 (17.9–68.6) months, respectively. The incidence rate of serious infections was 3.8 cases per 100 person-years. Antimalarial use (hazard ratio: 0.69; 95% confidence interval (CI): 0.48–0.99; p = 0.0440) was protective, while doses of prednisone >15 and ≤60 mg/day (hazard ratio: 4.18; 95 %CI: 1.69–10.31; p = 0.0019) and >60 mg/day (hazard ratio: 4.71; 95% CI: 1.35–16.49; p = 0.0153), use of methylprednisolone pulses (hazard ratio: 1.53; 95% CI: 1.10–2.13; p = 0.0124), increase in disease activity (hazard ratio: 1.03; 95% CI: 1.01–1.04; p = 0.0016) and damage accrual (hazard ratio: 1.22; 95% CI: 1.11–1.34; p < 0.0001) were predictive factors of serious infections.
Conclusions
Over time, prednisone doses higher than 15 mg/day, use of methylprednisolone pulses, increase in disease activity and damage accrual were predictive of infections, whereas antimalarial use was protective against them in SLE patients.
Background.
The role of surgery for lung metastases (LM) secondary to colorectal cancer (CRC) remains controversial. The bulk of evidence is derived from single surgical series, hampering any ...definitive conclusions. The aim of this study was to compare the outcomes of CRC patients with LM submitted to surgery with those who were not.
Patients and Methods.
Data from 409 patients with LM as the first evidence of advanced disease were extracted from a database of 1,411 patients. Patients were divided into three groups: G1, comprised of 155 patients with pulmonary and extrapulmonary metastases; G2, comprised of 104 patients with LM only and no surgery; G3, comprised of 50 patients with LM only and submitted to surgery.
Results.
No difference in response rates emerged between G1 and G2. Median progression‐free survival (PFS) times were: 10.3 months, 10.5 months, and 26.2 months for G1, G2, and G3, respectively. No difference in PFS times was observed between G1 and G2, whereas there was a statistically significant difference between G2 and G3. Median overall survival times were 24.2 months, 31.5 months, and 72.4 months, respectively. Survival times were longer in resected patients: 17 survived >5 years and three survived >10 years. In patients with LM only and no surgery, four survived for 5 years and none survived >10 years.
Conclusions.
Even though patients with resectable LM are more likely to be those with a better outcome, our study provides evidence suggesting an active role of surgery in improving survival outcomes in this patient subset.
摘要
背景： 对继发于结直肠癌（CRC）的肺转移（LM）灶，目前手术治疗的作用尚存有争议。大量证据来自单中心的手术系列病例报道，无法得出任何确切的结论。本研究旨在比较接受手术和未接受手术的CRC肺转移患者的转归。
患者和方法： 从1 411例患者的数据库提取出以肺转移作为结肠癌晚期首发征象的409例患者的数据。将患者分为三组：G1，包括155例有肺和肺外转移的患者；G2，包括104例仅有肺转移且未手术的患者；G3，包括50例仅有肺转移且接受手术的患者。
结果： G1和G2的缓解率无差异。G1、G2和G3的中位无进展生存（PFS）时间分别为10.3个月、10.5个月和26.2个月。G1和G2的PFS时间无差异，而G2和G3的PFS时间有统计学显著差异。G1、G2和G3的中位总生存时间分别为24.2个月、31.5个月和72.4个月。手术切除患者的生存时间更长：17例患者的生存时间> 5年，3例患者的生存时间> 10年。在仅有肺转移且未手术的患者中，4例患者生存5年，无一例患者生存时间超过10年。
结论： 虽然肺转移灶可切除患者更可能有更好的转归，但是本研究证据提示手术在改善肺转移灶可切除患者的生存转归中起到积极作用。
The outcomes of colorectal cancer patients with lung metastases submitted to surgery were compared with those who did not receive surgery. Evidence suggesting an active role of surgery in improving survival outcomes in this patient subset is presented.
Thymulin is a thymic hormone exclusively produced by the thymic epithelial cells. It consists of a nonapeptide component coupled to the ion zinc, which confers biological activity to the molecule. ...After its discovery in the early 1970s, thymulin was characterized as a thymic hormone involved in several aspects of intrathymic and extrathymic T cell differentiation. Subsequently, it was demonstrated that thymulin production and secretion is strongly influenced by the neuroendocrine system. Conversely, a growing core of information, to be reviewed here, points to thymulin as a hypophysotropic peptide. In recent years, interest has arisen in the potential use of thymulin as a therapeutic agent. Thymulin was shown to possess anti-inflammatory and analgesic properties in the brain. Furthermore, an adenoviral vector harboring a synthetic gene for thymulin, stereotaxically injected in the rat brain, achieved a much longer expression than the adenovirally mediated expression in the brain of other genes, thus suggesting that an anti-inflammatory activity of thymulin prevents the immune system from destroying virus-transduced brain cells. Other studies suggest that thymulin gene therapy may also be a suitable therapeutic strategy to prevent some of the endocrine and metabolic alterations that typically appear in thymus-deficient animal models. The present article briefly reviews the literature on the physiology, molecular biology, and therapeutic potential of thymulin.
CUPID-0 is the first large array of scintillating Zn 82 Se cryogenic calorimeters (bolometers) implementing particle identification for the search of the neutrinoless double beta decay (0 ν β β ). ...The detector consists of 24 enriched Zn 82 Se bolometers for a total 82 Se mass of 5.28 kg and it has been taking data in the underground LNGS (Italy) since March 2017. In this article we show how the dual read-out provides a powerful tool for the α particles rejection. The simultaneous use of the heat and light information allows us to reduce the background down to (3.2 − 1.1 + 1.3 )×10 − 3 counts/(keV kg year), an unprecedented level for cryogenic calorimeters. In a total exposure of 5.46 kg year Zn 82 Se we set the most stringent limit on the 0 ν β β decay 82 Se half-life T 1 / 2 0 ν > 4.0 × 10 24 year at 90% C.I.
Abstract
To evaluate disease characteristics of childhood onset SLE in Latin America and to compare this information with an adult population in the same cohort of GLADEL. A protocol was designed as ...a multicenter, multinational, inception cohort of lupus patients to evaluate demographic, clinical, laboratory and serological variables, as well as classification criteria, disease activity, organ damage and mortality. Descriptive statistics, chi square, Fisher's exact test, Student's t test and multiple logistic regression were used to compare childhood and adult onset SLE. 230 patients were < 18 years and 884 were adult SLE patients. Malar rash, fever, oral ulcers, thrombocytopenia and hemolytic anemia and some neurologic manifestations were more prevalent in children (p < 0.05). On the other hand, myalgias, Sjögren’s syndrome and cranial nerve involvement were more frequently seen in adults (p < 0.05). Afro-Latin-American children had a higher prevalence of fever, thrombocytopenia and hemolytic anemia. White and mestizo children had a higher prevalence of malar rash. Mestizo children had a higher prevalence of cerebrovascular disease and cranial nerve involvement. Children met SLE ACR criteria earlier with higher mean values than adults (p: 0.001). They also had higher disease activity scores (p: 0.01), whereas adults had greater disease damage (p: 0.02). In Latin America, childhood onset SLE seems to be a more severe disease than adults. Some differences can be detected among ethnic groups.
The implementation of experimental gene therapy in animal models of neurological diseases is an area of growing interest. Although the neuroendocrine system offers unique advantages for the ...assessment of in vivo gene therapy, little work has been done in this model. Here we review the core of documented studies in which in vivo gene therapy has been implemented in the neuroendocrine system of rodent models. In the hypothalamus, restorative gene therapy has been successfully implemented in Brattleboro rats, an arginine vasopressin (AVP) mutant which suffers from diabetes insipidus, in Koletsky (fa(k)/fa(k)) and in Zucker (fa/fa) rats which have leptin receptor mutations that render them obese, hyperphagic and hyperinsulinemic. In the above models, viral vectors expressing AVP, leptin receptor b and proopiomelanocortin, respectively were stereotaxically injected in the relevant hypothalamic regions. In rats, aging brings about a progressive degeneration and loss of hypothalamic tuberoinfundibular dopaminergic neurons, which are involved in the tonic inhibitory control of prolactin secretion and lactotrophic cell proliferation. Stereotaxic injection of an adenoviral vector expressing Insulin-like Growth Factor-I (IGF-I) was able to correct their chronic hyperprolactinemia and restore tuberoinfundibular dopaminergic (TIDA) neuron numbers. In young and old F-344 male rats, Glial Cell Line-derived Neurotrophic Factor (GDNF) gene delivery in the hypothalamus induced body weight loss. These results suggest that further implementation of gene therapy strategies in neuroendocrine models may be highly rewarding.
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