Background: Metagenomic next-generation sequencing (mNGS) demonstrates great promise as a diagnostic tool for determining the cause of pathogenic infections. The standard diagnostic procedures (SDP) include smears and cultures and are typically viewed as less sensitive and more time-consuming when compared to mNGS. There are concerns about the logistics and ease of transition from SDP to mNGS. mNGS lacks standardization of collection processes, databases, and sequencing. Additionally, there is the burden of training clinicians on interpreting mNGS results. background: Metagenomic next-generation sequencing (mNGS) demonstrates great promise as a diagnostic tool for determining the cause of pathogenic infections. The current standard diagnostic procedures (SDP) include smears and cultures and are typically viewed as less sensitive and more time-consuming when compared to mNGS. There are concerns about the logistics and ease of transition from SDP to mNGS. mNGS lacks standardization of collection processes, databases, and sequencing. Additionally, there is the burden of training clinicians on interpreting mNGS results. Objective: Until now, few studies have explored factors that could be used as early adoption candidates to ease the transition between SDP and mNGS. This study evaluated 123 patients who had received both SDP and mNGS and compared several variables across a diagnostic test evaluation. objective: Until now, few studies have explored factors that could be used as early adoption candidates to ease the transition between current diagnostic procedures and mNGS. This study evaluated 123 patients who had received both SDP and mNGS and compared several variables across a diagnostic test evaluation. Methods: The diagnostic test evaluation observed metrics such as sensitivity, specificity, positive and negative likelihood ratios (PLR, NLR), positive and negative predictive values (PPV, NPV), and accuracy. Factors included various sample sources such as bronchoalveolar lavage fluid (BALF), lung tissue, and cerebral spinal fluid (CSF). An additional factor observed was the patient's immune status. Results: Pathogen detection was found to be significantly greater for mNGS for total patients, BALF sample source, CSF sample source, and non-immunocompromised patients (p<0.05). Pathogen detection was found to be insignificant for lung tissue sample sources and immunocompromised patients. Sensitivity, PLR, NLR, PPV, NPV, and accuracy appeared to be higher with mNGS for the total patients, BALF sample source, and non-immunocompromised patients when compared with SDP (p<0.05). result: Disease detection was found to be significantly different (p&lt;0&gt;0.05) for lung tissue sample sources and immunocompromised patients. Sensitivity, PLR, NLR, PPV, NPV, and accuracy appeared to be higher for the total patients, BALF sample source, and non-immunocompromised patients when comparing mNGS and SDP. Conclusion: With higher metrics in sensitivity, specificity, PLR, NLR, PPV, NPV, and accuracy for overall patients, mNGS may prove a better diagnostic tool than SDP. When addressing sample sources, mNGS for BALF-collected samples appeared to have higher scores than SDP for the same metrics. When patients were in a non-immunocompromised state, mNGS also demonstrated greater diagnostic benefits to BALF and overall patients compared to SDP. This study demonstrates that using BALF as a sample source and selecting non-immunocompromised patients may prove beneficial as early adoption factors for mNGS standard protocol. Such a study may pave the road for mNGS as a routine clinical method for determining the exact pathogenic etiology of lung infections.

中文翻译：

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确定呼吸系统感染宏基因组下一代测序早期采用和标准化的理想因素

背景：宏基因组下一代测序（mNGS）显示出作为确定致病性感染原因的诊断工具的巨大前景。标准诊断程序 (SDP) 包括涂片和培养，与 mNGS 相比，通常被认为灵敏度较低且更耗时。人们对从 SDP 到 mNGS 过渡的物流和难易程度感到担忧。mNGS 缺乏采集流程、数据库和测序的标准化。此外，还存在培训临床医生解释 mNGS 结果的负担。背景：宏基因组下一代测序（mNGS）显示出作为确定致病性感染原因的诊断工具的巨大前景。当前的标准诊断程序 (SDP) 包括涂片和培养，与 mNGS 相比，通常被认为灵敏度较低且更耗时。人们对从 SDP 到 mNGS 过渡的物流和难易程度感到担忧。mNGS 缺乏采集流程、数据库和测序的标准化。此外，还存在培训临床医生解释 mNGS 结果的负担。目标：到目前为止，很少有研究探索可作为早期采用候选因素以简化 SDP 和 mNGS 之间过渡的因素。这项研究评估了 123 名接受过 SDP 和 mNGS 的患者，并比较了诊断测试评估中的几个变量。目标：到目前为止，很少有研究探索可作为早期采用候选因素以简化当前诊断程序和 mNGS 之间过渡的因素。这项研究评估了 123 名接受过 SDP 和 mNGS 的患者，并比较了诊断测试评估中的几个变量。方法：诊断测试评估观察灵敏度、特异性、阳性和阴性似然比（PLR、NLR）、阳性和阴性预测值（PPV、NPV）和准确性等指标。因素包括各种样本来源，例如支气管肺泡灌洗液 (BALF)、肺组织和脑脊液 (CSF)。观察到的另一个因素是患者的免疫状态。结果：发现 mNGS 对总患者、BALF 样本源、CSF 样本源和非免疫功能低下患者的病原体检测显着更高 (p<0.05)。研究发现，病原体检测对于肺组织样本来源和免疫功能低下的患者来说意义不大。与 SDP 相比，mNGS 对于总患者、BALF 样本来源和非免疫功能低下患者的敏感性、PLR、NLR、PPV、NPV 和准确性似乎更高 (p<0.05)。结果：发现肺组织样品来源和免疫受损患者的疾病检测显着不同(p＜0.05)。比较 mNGS 和 SDP 时，总患者、BALF 样本来源和非免疫功能低下患者的灵敏度、PLR、NLR、PPV、NPV 和准确性似乎更高。结论：mNGS 具有更高的灵敏度、特异性、PLR、NLR、PPV、NPV 和整体患者准确度指标，可能会被证明是比 SDP 更好的诊断工具。在解决样本来源问题时，对于相同指标，BALF 收集样本的 mNGS 得分似乎高于 SDP。当患者处于非免疫功能低下状态时，与 SDP 相比，mNGS 还表现出对 BALF 和整体患者更大的诊断益处。这项研究表明，使用 BALF 作为样本来源并选择非免疫功能低下的患者可能会被证明是有益的，作为 mNGS 标准方案的早期采用因素。这样的研究可能为 mNGS 作为确定肺部感染确切致病病因的常规临床方法铺平道路。