Diagnostic significance of the histopathology of bone marrow macrophages in forensic autopsies

Forensic pathologists often encounter autopsies that require an assessment of antemortem general conditions (e.g., infection, metabolic disorders). To establish evaluation clues for such cases, we quantitatively examined macrophages and the general pathology of bone marrow in samples from 180 forensic autopsy cases of decedents with various conditions. Hematoxylin-eosin staining, Berlin blue staining, and immunostainings for CD163, CD138, and CD61 were performed. We determined the numbers per field (density) of total macrophages, swollen macrophages, macrophages with hemophagocytosis, and hemosiderin-laden macrophages. Each density was standardized by identifying its ratio to the total number of macrophages. The decedents' background data (cause of death, other pathological findings, postmortem interval, antemortem symptoms, and presence of resuscitation) were extracted. No correlations were found between the postmortem interval and the other decedent data, indicating that these data are not affected by postmortem changes. In the group in which inflammatory disease was the cause of death, there were significant elevations in the ratio of the swollen macrophage density to total macrophages. Significantly higher ratios of the density of swollen and hemophagocytic macrophages were observed in the group in which conditions with a prolonged agonal period were the cause of death. The group with a return of spontaneous circulation to resuscitation showed a significantly higher ratio of macrophage density with hemophagocytosis. This study provides the first statistical analysis focused on bone marrow histopathology in forensic autopsies. The results will be useful for elucidating causes of death and agonal-period conditions.     

Understanding congenital vertical talus

Congenital vertical talus (CVT) is a rare foot deformity that presents with a rigid flat foot at birth. CVT can present as an isolated abnormality in the newborn, however in at least 50% of cases in association with other conditions. Full neuro-axial imaging is essential to detect any associated neurologic problems. Radiographs of the foot, including forced plantar and dorsiflexion laterals, are diagnostic. Gold standard modern treatment uses the Dobbs method of serial manipulation and casting with minimally-invasive stabilization of the talonavicular joint and Achilles tendon tenotomy.     

The impact of the updated EORTC/MSG criteria on the classification of hematological patients with suspected invasive pulmonary aspergillosis

ObjectivesOur aim was to evaluate the effect of the updated European Organization for Research and Treatment of Cancer (EORTC) and Mycoses Study Group 2019 definitions for invasive pulmonary aspergillosis (IPA) on patient classification and the related all-cause 12-week mortality.MethodsIn this retrospective cohort study from our tertiary care centre, we reclassified patients with haematological malignancy who underwent bronchoalveolar lavage between 2014 and 2019 for suspected IPA using the novel EORTC 2019 criteria. We performed receiver operating characteristic curve analysis to define the optimal cut-off for positive PCR and galactomannan and present survival analyses and their possible association with these diagnostic criteria through post hoc comparisons with log rank and Cox regression.ResultsFrom 323 episodes of suspected IPA in 282 patients, 73 were reclassified: 31 (42.5%) from possible to probable IPA, 5 (6.8%) from EORTC criteria not met to probable IPA, and 37 (50.7%) from EORTC criteria not met to possible IPA. Probable IPA increased therefore 11.1% (64/323, 19.8% to 100/323, 30.9%), mostly due to positive PCR (31/36, 86.1%). There was no difference in mortality between newly defined possible and probable IPA (log rank p = 0.950). Mortality was higher in probable cases with lower cycle thresholds (Ct values) versus higher Ct values (p = 0.004). Receiver operating characteristic curve analysis showed an optimal Ct value cut-off of 36.8 with a sensitivity of 75% (95% CI 64.9%–85.1%) and a specificity of 61.7% (95% CI 53.5–69.9) for 12-week mortality.DiscussionThe new EORTC criteria led to 11.1% more probable IPA diagnoses, mostly due to Aspergillus PCR. Restricting positive PCR to below a certain threshold might improve the discrimination of the new EORTC IPA categories for mortality.     

Effects of the Clearing the Lung and Dissipating Phlegm Method in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Objective: The objective of this study is to evaluate the efficacy and safety of the clearing the lung and dissipating phlegm method in the treatment of acute exacerbation of chronic obstructive pulmonary disease(COPD) and to provide evidence for the treatment of the disease. Materials and Methods: Literature was searched from the United States National Library of Medicine(PubMed), Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database(Wanfang), and the Full?Text Database of Chinese Scientific and Technical Periodicals(VIP).A comprehensive collection was made of randomized controlled trials(RCTs) before June 2018, in which the treatment groups used either the clearing the lung and dissipating phlegm formulas only or combined it with routine Western medicine therapy, and the control group adopted routine Western medicine therapy only for the acute exacerbation of COPD. The Cochrane risk of bias method was used to evaluate the quality of the literature. The data were analyzed and retrieved independently by two reviewers before meta?analysis was carried out with RevMan 5.3 software to evaluate the primary outcome measures, including the total clinical effective rate, and the secondary outcome measures such as the pulmonary function(forced vital capacity [FVC], forced expiratory volume in the 1 s [FEV1], percentage of FEV1 [FEV1%], and FEV1/FVC)and blood gases(PaO_2 and PaCo_2). Results: A total of 13 RCTs involving 990 patients(496 in the treatment group and 494 in the control group)were included in this study. Meta?analysis revealed significant difference in the efficacy of the group that adopted solely the routine Western medicine method and the group that combined the Western medicine with the clearing the lung and dissipating phlegm method. Outcome measures including the pulmonary function(FVC, FEV1, FEV1%, and FEV1/FVC) and the blood gases(PaO_2 and PaCo_2) were significantly improved as compared to the control group(P 0.00001). However, adverse effects in the treatment group using combined traditional Chinese medicine were not reported due to the short observation time of the study. Conclusion: The clearing the lung and dissipating phlegm method can improve the efficacy in the treatment of acute exacerbation of COPD, the outcome measures of the pulmonary function and the blood gases,as well as the life quality of the patients. However, due to the fact that the existing studies are generally of poor quality in which randomization and its implementation were not properly carried out, more high?quality RCTs are necessary to confirm the findings of this study.     

骨形态发生蛋白2及碱性成纤维生长因子2对大鼠骨髓间充质干细胞膜片增殖和成骨分化的影响

文题释义： 细胞膜片技术：是在体外接种培养高密度的细胞，使其相互融合生长至100%而形成的透明致密膜状物。该技术不需要胰酶消化即可收集细胞，因此保留了大量的胞外基质、细胞间连接以及细胞-基质连接等结构。目前细胞膜片技术已成为组织工程领域的研究热点，已被推广应用于牙周膜、角膜、心脏、软骨、食管等多种组织器官修复。 成骨细胞：主要由内外骨膜和间充质始祖细胞分化而来，在复杂的骨形成过程中发挥着主要的功能，承担着骨基质的合成、分泌和矿化。骨髓间充质干细胞具有多向分化潜能，能定向分化为成骨细胞，其成骨分化过程可受多种因素的影响，如细胞因子的调控、遗传因素和激素水平等。背景：现阶段骨形态发生蛋白2和碱性成纤维生长因子2对骨髓间充质干细胞膜片增殖、成骨分化的影响和作用机制还尚未可知，如何将生长因子与组织工程细胞膜片技术相整合，最终将其用于骨缺损修复具有重要意义。 目的：探讨单独及联合应用骨形态发生蛋白2和碱性成纤维生长因子2对骨髓间充质干细胞膜片增殖和成骨分化的影响。 方法：体外分离培养鉴定SD大鼠骨髓间充质干细胞并构建细胞膜片，选用不同质量浓度的骨形态发生蛋白2和碱性成纤维生长因子2单独及联合诱导骨髓间充质干细胞膜片，CCK-8法结合碱性磷酸酶活性检测确定2种因子促进膜片增殖和成骨分化的最佳有效质量浓度；然后对骨髓间充质干细胞膜片进行成骨诱导，通过大体及显微镜观察、Vonkossa染色、茜素红染色、RT-PCR检测相关成骨标志物来评估诱导效果。 结果与结论：单独应用骨形态发生蛋白2可增强骨髓间充质干细胞膜片的碱性磷酸酶活性，最佳质量浓度为100 μg/L(P < 0.001)，单独应用碱性成纤维生长因子2能加速骨髓间充质干细胞膜片的增殖，最佳质量浓度为20 μg/L(P < 0.001)，而联合应用既可以促进膜片增殖又能提高其碱性磷酸酶活性(P < 0.001)；经成骨诱导后，4组膜片在形态学上无明显差异，均能诱导骨髓间充质干细胞膜片的成骨分化，其中联合组钙结节最明显(P < 0.001)，可显著促进膜片晚期成骨分化并抑制其早期成骨分化，具有明显的协同促进作用(P < 0.001)。结果表明，骨形态发生蛋白2和碱性成纤维生长因子2联合应用时具有协同作用，既可以促进骨髓间充质干细胞膜片增殖，又能显著增强其成骨诱导能力。ORCID: 0000-0003-1918-579X(何惠宇) 中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程     

肺癌脑转移放射治疗方式及进展

肺癌是发病率和死亡率最高的恶性肿瘤，其脑转移发生率高且预后差。近年来随着靶向以及免疫治疗药物相继研制成功，肺癌原发灶局部控制率得以提升，因此对其脑转移的治疗更加关注。放射治疗是肺癌脑转移治疗的重要手段之一，现将肺癌脑转移放射治疗方式及进展进行综述。