Accuracy of prehospital triage systems for mass casualty incidents in trauma register studies - A systematic review and meta-analysis of diagnostic test accuracy studies

BackgroundPrioritising patients in mass casualty incidents (MCI) can be extremely difficult. Therefore, triage systems are important in every emergency medical service. This study reviews the accuracy of primary triage systems for MCI in trauma register studies.MethodsWe registered a protocol at PROSPERO ID: CRD42018115438. We searched MEDLINE, EMBASE, Central, Web of Science, Scopus, Clinical Trials, Google Scholar, and reference lists for eligible studies. We included studies that both examined a primary triage system for MCI in trauma registers and provided sensitivity and specificity for critically injured vs non-critically injured as results. We excluded studies that used paediatric, chemical, biological, radiological or nuclear MCIs populations or triage systems. Finally, we calculated intra-study relative sensitivity, specificity and diagnostic odds ratio for each triage system.ResultsTriage Sieve (TS) significantly underperformed in relative diagnostic odds ratio (DOR) when compared to START and CareFlight (CF) (START vs TS: 19.85 vs 13.23 (p<0.0001)│CF vs TS: 23.72 vs 12.83 (p<0.0001)). There was no significant difference in DOR between TS and Military Sieve (MS) (p<0.710). Compared to START, MS and CF TS had significantly higher relative specificity (START vs TS: 93.6% vs 96.1% (p=0.047)│CF vs TS: 96% vs 95.3% (p=0.0006)│MS vs TS: 94% vs 88.3% (p=0.0002)) and lower relative sensitivity (START vs TS: 57.8% vs 34.8% (p<0.0001)│CF vs TS: 53.9% vs 34.7% (p<0.0001)│MS vs TS: 51.9% vs 35.2% p<0.0001)).CF had significantly better relative DOR than START (CF vs START: 23.56 vs 27.79 (p=0.043)). MS had significantly better relative sensitivity than CF and START (MS vs CF: 49.5% vs 38.7% (p<0.0001)│MS vs START: 49.4% vs 43.9% (p=0.01)). In contrast, CF had significantly better relative specificity than MS (MS vs CF: 91.3% vs 93.3% (p<0.0001)). The remaining comparisons did not yield any significant differences.ConclusionAs the included studies were at risk of bias and had heterogenic characteristics, our results should be interpreted with caution. Nonetheless, our results point towards inferior accuracy of Triage Sieve compared to START and CareFlight, and less firmly point towards superior accuracy of Military Sieve compared to START, CareFlight and Triage Sieve     

Immunohistochemical and molecular analysis of PI3K/AKT/mTOR pathway in esophageal carcinoma

Among the numerous signaling pathways involved in tumorigenesis, PI3K‐AKT‐mTOR is a key one that regulates diverse cellular functions. However, its prognostic value in esophageal carcinoma remains unclear. In our study, we examined the immunohistochemical expression of phosphorylated (p‐) AKT, mTOR, p70S6K and 4E‐BP1 along with the mutational status of PIK3CA and AKT1 genes by High Resolution Melting Analysis and Pyrosequencing in 44 esophageal carcinomas. The results were correlated with the clinicopathological characteristics of the patients in an effort to define their possible prognostic significance. Total p‐mTOR cytoplasmic expression, assessed in 10 random areas, was positively correlated with tumor stage (Kruskal–Wallis ANOVA, I/II vs III/IV, p = 0.0500). Μoreover, maximum p‐mTOR cytoplasmic immunoexpression, estimated in hot spot areas, was positively associated with tumor grade (Mann–Whitney U test, I/II vs III, p = 0.0565). Interestingly, p‐4E‐BP1 immunoreactivity was negatively correlated with tumor histological grade (Mann–Whitney U test, I/II vs III, p = 0.0427). No mutation was observed in exons 9 and 20 of PIK3CA gene and in exon 4 of AKT1 gene. In conclusion, our findings depict the presence of activated PI3K/AKT/mTOR pathway in esophageal cancer bringing forward p‐mTOR and p‐4E‐BP1 for their potential role in esophageal carcinogenesis. Additional studies are warranted to validate our findings.     

红景天苷通过TLR4调控DC提高T细胞对肺癌3LL细胞的杀伤力

目的：探讨红景天苷（salidroside，SAL）对树突状细胞（dendritic cell，DC）表型及细胞毒性T细胞（cytotoxic T lympho‐cyte，CTL）抗肿瘤能力的影响。方法：选用Lewis肺癌细胞株3LL、野生型C57BL/6和TLR4-/-C57BL/6小鼠，获取小鼠骨髓来源的DC前体细胞，经过培养分化成未成熟DC，收获第6天的DC，经磁珠分选后获得纯度较高的CD11c+DC。将细胞分成PBS组、SAL组和脂多糖（lipopolysaccharide，LPS）组，培养48 h后用流式细胞术检测SAL体外对DC表面分子、吞噬功能、TLR4通路和对T细胞杀伤能力的影响。结果：与 PBS 组比较，SAL组DC的表面分子CD80、CD86、MHC Ⅱ表达水平显著升高（均 P<0.05）、吞噬功能显著下降（P<0.05）、TLR4 表达水平显著升高（P<0.01）；与野生型组比较，TLR4-/-组DC经SAL或LPS处理后，其表面分子CD80、CD86、MHC Ⅱ的表达水平显著降低（均P<0.05）；与PBS组比较，SAL组刺激活化的CTL对肺癌3LL细胞的杀伤效应显著升高（P<0.05）。结论：SAL可以通过调控TLR4诱导DC成熟，从而提高T细胞的杀伤能力     

Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

High-Frequency Irreversible Electroporation Using 5,000-V Waveforms to Create Reproducible 2- and 4-cm Ablation Zones—A Laboratory Investigation Using Mechanically Perfused Liver

PurposeTo investigate if high-frequency irreversible electroporation (H-FIRE) treatments can be delivered at higher voltages and with greater energy delivery rates than currently implemented in clinical irreversible electroporation protocols.Materials and MethodsTreatments using 3,000 V and 5,000 V were administered to mechanically perfused ex vivo porcine liver via a single applicator and grounding pad (A+GP) as well as a 4-applicator array (4AA). Integrated energized times (IET) 0.01–0.08 seconds and energy delivery rates 25–300 μs/s were investigated. Organs were preserved at 4°C for 10–15 hours before sectioning and gross analysis using a metabolic stain to identify the size and shape of ablation zones.ResultsA+GP ablations measured between 1.6 cm and 2.2 cm, which did not increase when IET was increased from 0.02 seconds to 0.08 seconds (P > .055; range, 1.9–2.1 cm). Changes in tissue color and texture consistent with thermal damage were observed for treatments with energy delivery rates 50–300 μs/s, but not for treatments delivered at 25 μs/s. Use of the 4AA with a 3-cm applicator spacing resulted in ablations measuring 4.4–4.9 cm with energy delivery times of 7–80 minutes.ConclusionsH-FIRE treatments can rapidly and reproducibly create 2-cm ablations using an A+GP configuration. Treatments without thermal injury were produced at the expense of extended treatment times. More rapid treatments resulted in ablations with varying degrees of thermal injury within the H-FIRE ablation zone. Production of 4-cm ablations is possible using a 4AA.     

Imaging Features of Pulmonary Immune-related Adverse Events

Pulmonary immune-related adverse events represent rare but potentially severe side effects of immunotherapies. Diagnosis is often challenging, as symptoms and imaging features are not specific and may mimic other lung diseases, thus potentially delaying appropriate patient management. In this setting, an accurate imaging evaluation is essential for a prompt detection and correct management of these drug-induced lung diseases. The purpose of this article is to review the different types of pulmonary immune-related adverse events, describe their imaging characteristics on both high-resolution computed tomography and positron emission tomography/computed tomography and stress their underlying diagnostic challenge by presenting the mimickers.     

化浊清解愈溃煎对溃疡性结肠炎大鼠p38MAPK、TNF-α、IL-4的影响

目的观察化浊清解愈溃煎对溃疡性结肠炎(UC)大鼠血清及结肠组织p38MAPK、肿瘤坏死因子-α(TNF-α)、白细胞介素-4(IL-4)含量的影响。方法清洁级Wistar雄性大鼠50只按随机数字表法分为两组,空白组8只,其余大鼠均为造模组。采用TNBS/乙醇联合造模法构建UC大鼠模型。造模成功后按照随机数字表法将模型大鼠分为模型组、西药组(予美沙拉嗪肠溶片混悬液0.42 g/kg)及中药高、中、低剂量组。中药高、中、低剂量组予化浊清解愈溃煎中药混悬液,剂量分别为22、11、5.5 g/(kg·d),每日灌胃1次,疗程14 d。采用免疫组化法检测各组大鼠结肠组织内p38MAPK的蛋白表达量。ELISA法检测各组大鼠血清内TNF-α、IL-4含量。结果与空白组比较,模型组一般情况较差,血清中TNF-α含量显著升高(P<0.05),IL-4含量则明显降低(P<0.05),结肠组织中p38MAPK水平明显升高(P<0.05)。与模型组比较,西药组、中药各剂量组大鼠一般生存状况改善明显,血清中TNF-α含量下降,IL-4含量明显升高,尤以中药高剂量组和西药组疗效显著(P<0.05)。结论化浊清解愈溃煎高、中剂量可改善UC大鼠一般生存状况,并通过调节血清中IL-4含量,下调TNF-α表达水平和结肠组织中p38MAPK蛋白表达水平而达到保护结肠黏膜和治疗UC的作用。     

Clinical Implication of Toll-Like Receptors (TLR2 and TLR4) in Acute Myeloid Leukemia Patients

Backgrounds: Toll-like receptors 2; 4 (TLR2;4) are an essential component of the innate immunity and play an important role in immune-surveillance and immune response to various microorganisms. This study aimed to investigate the association between TLR2 and TLR4 polymorphism and the risk of acquiring severe infections, and impact on AML patient’s outcome. Subjects and methods: Using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP); we analyzed three SNPs in the TLR2 (Arg753Gln) and TLR4 (Asp299Gly and Thr399Ile) in 120 AML patients and 100 healthy control subjects. Results: No significant differences in genotype or alleles frequency between healthy controls and AML patients regarding TLR2 Arg753Gln, TLR4 Asp299Gly and TLR4 Thr399Ile polymorphisms (P>0.05 for all). Neutropenic fever was detected in 110 out of 120 (91.7%) of the studied AML patients. The sepsis and pneumonia were identified in 20 out of 120 patients (16.7%). The incidence of sepsis was associated with TLR2 Arg753Gln: AG genotypes, A allele and TLR4 Asp299Gly: CT genotype and C allele as compared to other genotypes and alleles. Moreover; TLR2 (Arg753Gln) GG polymorphisms significantly associated with shortest overall survival (OS) and shortest disease-free survival (DFS); while TLR4 polymorphisms affect the DSF only but not OS. In AML patients TLR2 Arg753Gln gene polymorphism is associated with high susceptibility to sepsis and TLR4 (Asp299Gly and Thr399Ile) gene polymorphism is associated with high susceptibility for both pneumonia; and sepsis. Conclusion: TLR2 Arg753Gln (AG; GG genotype) polymorphisms are associated with shortest OS and DFS. Moreover; significant association between TLR2 polymorphisms, TLR4 Arg753Gln polymorphisms and risk of severe infections in AML patients was documented.