Lung Screening Benefits and Challenges: A Review of The Data and Outline for Implementation

Lung cancer is the leading cause of cancer-related deaths worldwide, accounting for almost a fifth of all cancer-related deaths. Annual computed tomographic lung cancer screening (CTLS) detects lung cancer at earlier stages and reduces lung cancer-related mortality among high-risk individuals. Many medical organizations, including the U.S. Preventive Services Task Force, recommend annual CTLS in high-risk populations. However, fewer than 5% of individuals worldwide at high risk for lung cancer have undergone screening. In large part, this is owing to delayed implementation of CTLS in many countries throughout the world. Factors contributing to low uptake in countries with longstanding CTLS endorsement, such as the United States, include lack of patient and clinician awareness of current recommendations in favor of CTLS and clinician concerns about CTLS-related radiation exposure, false-positive results, overdiagnosis, and cost. This review of the literature serves to address these concerns by evaluating the potential risks and benefits of CTLS. Review of key components of a lung screening program, along with an updated shared decision aid, provides guidance for program development and optimization. Review of studies evaluating the population considered “high-risk” is included as this may affect future guidelines within the United States and other countries considering lung screening implementation.     

Circulating histocompatibility antigen (HLA) gene products may help differentiate benign from malignant indeterminate pulmonary lesions

Background

This study explores the potential diagnostic utility of soluble Human Leukocyte Antigen (sHLA) molecules differentially released by lung adenocarcinoma and benign lung lesions.

腹部低剂量CT技术的临床应用

本文介绍了迭代重建算法、非对称性屏蔽采集、X-Care等7种CT低剂量技术及在腹部扫描中的临床应用。在保证CT图像质量能满足诊断要求的前提下,尽可能降低辐射剂量是目前普遍关注的问题。腹部CT检查一般要进行多期增强扫描,与其他部位相比,病人接受的辐射量将成倍增加,损害人类健康,所以有必要采用低剂量扫描方式。     

Cell division cycle 25 homolog c effects on low-dose hyper-radiosensitivity and induced radioresistance at elevated dosage in A549 cells

The underlying mechanisms behind both low-dose hyper-radiosensitivity (HRS) and induced radioresistance (IRR), generally occurring at elevated radiation levels, remain unclear; however, elucidation of the relationship between cell cycle division 25 homolog c (Cdc25c) phosphatase and HRS/IRR may provide important insights into this process. Two cell lines with disparate HRS status, A549 and SiHa cells, were selected as cell models for comparison of dose-dependent Cdc25c phosphatase expression subsequent to low-dose irradiation. Knockdown of Cdc25c in A549 cells was mediated by transfection with a pGCsi-RAN-U6neo vector containing hairpin siRNA sequences. S216-phosphorylated Cdc25c protein [p-Cdc25c (Ser216)], cell survival and mitotic ratio were measured by western blot, colony-forming assay and histone H3 phosphorylation analysis. Variant p-Cdc25c (Ser216) expression was observed in the two cell lines after irradiation. The p-Cdc25c (Ser216) expression noted in SiHa cells after administration of 0–1 Gy radiation was similar to the radioresistance model; however, in A549 cells, the dose response for the phosphorylation of the Cdc25c Ser216 residue overlapped the level required to overcome the HRS response. Furthermore, Cdc25c repression prior to low-dose radiation induced more distinct HRS and prevented the development of IRR. The dose required to overcome the HRS response coincided with the effect of early G2-phase checkpoint arrest in A549 cells (approximately 0.3 Gy), and Cdc25c knockdown in A549 cells (approximately 0.5 Gy) corresponded to the phosphorylation of the Cdc25c Ser216 residue. Resultant data confirmed that dose-dependent Cdc25c phosphatase does effectively act as an early G2-phase checkpoint, thus indicating mechanistic importance in the HRS to IRR transition in A549 cells.     

Transfusion of platelet concentrates cryopreserved with ThromboSol plus low-dose dimethylsulphoxide in patients with severe thrombocytopenia: a pilot study

We have recently reported the possibility of supporting the phase of severe thrombocytopenia after high-dose chemotherapy (HDC) and stem cell transplantation using 5% dimethylsulphoxide (DMSO)-cryopreserved autologous platelet concentrates (PCs). The aim of the present study was to evaluate the therapeutic potential of ThromboSol (a recently developed platelet storage solution) plus PCs cryopreserved in 2% DMSO in patients undergoing myeloablative chemotherapy and autologous transplantation. PCs were collected from 14 women with breast cancer by a single plateletapheresis and cryopreserved in ThromboSol/2% DMSO by either direct insertion in a -80 degrees C freezer or in liquid nitrogen after computer-controlled rate (CR) freezing. When required, PCs were thawed, centrifuged to remove the cryoprotectants and transfused. In vitro studies on thawed platelets showed loss of epitopes of surface glycoproteins and a marked reduction of functional activity compared with fresh platelets. Transfusion of CR-frozen PCs was associated with a mean 1 h corrected count increment (CCI) of 9.2 +/- 5.4 x 109/l and only one allogeneic PC was required in this group. In contrast, six out of seven patients required additional allogeneic transfusions in the -80 degrees C group (CCI = 2.7 +/- 1.4 x 109/l). ThromboSol-treated PCs have the ability to overcome thrombocytopenia if processed by a CR freezing protocol, but appear ineffective when frozen by direct placing at -80 degrees C.     

The effects of a low-dose intravenous insulin infusion upon plasma glucose and non-esterified fatty acid levels in very obese and non-obese human subjects

Summary After an overnight fast, the effects of a 30-min low-dose intravenous insulin infusion (2.6 units/h) upon plasma glucose and non-esterified fatty acids were compared in 29 very obese patients and 17 nonobese controls. The dose of insulin was chosen so as to have its sole or predominant hypoglycaemic effect upon hepatic glucose release. The proportional fall from basal values at 30 min of both plasma glucose and non-esterified fatty acids was significantly greater in the controls and there was no difference between males and females. In the controls the fall in plasma glucose and non-esterified fatty acids was significantly and inversely correlated with the basal plasma insulin level. Neither index of insulin sensitivity was significantly related with the basal plasma insulin in the obese subjects. Weight loss in the obese subjects led to increased insulin sensitivity; in particular, the degree of change in insulin-induced nonesterified fatty acids was significantly related to the percentage change in weight. Despite their extreme degree of obesity, the distributions of basal plasma insulin levels and the indices of insulin sensitivity in the obese subjects overlapped with those of the nonobese controls.     

低剂量CT联合血清P16甲基化检测在肺癌早期诊断中的研究

目的研究在无症状的肺癌高危人群中低剂量CT(LDCT)联合血清P16基因甲基化检测对肺癌早期诊断的可行性。方法405例受试者随机分入LDCT P16甲基化检测组(221例)和前后位胸片(CXR)组(184例)。入选标准为男性,55~75岁,吸烟指数≥200年支。结果LDCT P16甲基化组97.7%(216例)和CXR组93.5%(173例)的受试者完成检测。LDCT P16甲基化组与CXR组分别有22例(10.2%)和13例(7.5%)可疑肺癌,3例及1例确诊肺癌。结论LDCT联合P16基因甲基化检测比CXR检查发现更多的肺癌。     

The anti-diabetogenic effect of essential fatty acid deficiency in multiple low-dose streptozotocin-treated mice persists if essential fatty acid repletion occurs outside of a brief window of susceptibility

Summary We have previously shown that essential fatty acid deficiency prevents diabetes mellitus and ameliorates insulitis in multiple low-dose streptozotocin-treated male CD-1 mice and that repletion with 99% pure methyl linoleate 3 days after the last injection causes diabetes. In the present study, we examined whether repletion of low-dose streptozotocin-treated deficient mice will cause diabetes whenever repletion occurs. Essential fatty acid deficiency was induced by dietary manipulation and was confirmed biochemically. Groups of deficient mice were repleted 6 h, 1 week, 2 weeks, 4 weeks and 8 weeks after the last low-dose streptozotocin treatment; the incidence of diabetes (i.e., non-fasting plasma glucose levels > 11.2 mmol/l) and group mean plasma glucose levels were 93% (19.4 mmol/l), 37% (14.8 mmol/l), 40% (13.7 mmol/l), 20% (9.0 mmol/l), and 8% (7.8 mmol/l) respectively. The incidence and mean glucose levels for low-dose streptozotocin-induced control chow-fed and non-repleted essential fatty acid deficient CD-1 mice were 100% (30.2 mmol/l) and 0% (4.2 mmol/l). The incidence and severity of insulitis also decreased with increasing repletion intervals. These results demonstrate a brief window of susceptibility of less than 8 weeks duration during which repletion will initiate an autoimmune response directed at low-dose streptozotocin-induced Beta-cell neoantigens in low-dose streptozotocin-treated essential fatty acid deficient mice.     

Low-dose dobutamine stress test for the evaluation of cardiac function using ultrafast computed tomography

High dose-dobutamine (DOB) has been previously used as a pharmacological stress test to evaluate wall motion abnormalities. As a result, recent stress echocardiography with low-dose DOB has been reported to be valuable for investigating stunned myocardium after thrombolysis. However, echocardiography requires an operator's skill and experience to evaluate wall motion abnormalities which are subjectively determined by the observer. In contrast, ultrafast computed tomography (UFCT) does not necessarily require extreme technical skill and experience. To evaluate the feasibility of stress UFCT with low-dose DOB, we scanned 10 normal subjects along the short-axis by 8-slice-multicine mode. After scanning at rest for baseline, we scanned during the administration of 4 and 8 m?g/kg/min of DOB, respectively, for 5 min. Ejection fraction, contraction, and thickening were higher during 8 m?g/kg/min of DOB than during 4 m?g/kg/min of DOB and baseline, while the above values were higher during 4 m?g/kg/min of DOB than during baseline (p < 0.01). It was possible to detect changes of cardiac function and wall motion due to low-dose DOB by UFCT. We therefore conclude that UFCT is a reliable modality for evaluating cardiac function and wall motion for low-dose DOB stress test because of its excellent spatial and contrast resolution.