The T2Bacteria Assay Is a Sensitive and Rapid Detector of Bacteremia That Can Be Initiated in the Emergency Department and Has Potential to Favorably Influence Subsequent Therapy

BackgroundBacteremia causes a major worldwide burden, in terms of financial and productivity costs, as well the morbidity and mortality it can ultimately cause. Proper treatment of bacteremia is a challenge because of the species-dependent response to antibiotics. The T2Bacteria Panel is a U.S. Food and Drug Administration–cleared and culture-independent assay for detection of bacteremia, including common ESKAPE pathogens—Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa—and provides species identification in as little as 3.6 h directly from blood.ObjectiveOur aim was to evaluate the T2Bacteria assay performance and potential to affect patient care in the emergency department (ED).MethodsED patients from a Louisiana and Florida center were enrolled as part of the T2Bacteria Panel clinical study, which was prospective and noninterventional. Blood samples for blood culture (BC) and T2Bacteria were matched in time and anatomic location.ResultsData from 137 ED patients were evaluated. Relative to BC, T2Bacteria showed 100% positive percent agreement and 98.4% negative percent agreement. In addition, for species on the T2Bacteria Panel, the T2Bacteria assay detected 25% more positives associated with infection, and on average identified the infectious species 56.6 h faster. The T2Bacteria assay covered 70.5% of all species detected by BC. Finally, relative to actual care, the T2Bacteria assay could have potentially focused therapy in 8 patients, reduced time to a species-directed therapy in 4 patients, and reduced time to effective therapy in 4 patients.ConclusionsIn this ED population, the T2Bacteria assay was a rapid and sensitive detector of bacteremia from common ESKAPE pathogens and showed the theoretical potential to influence subsequent patient therapy, ranging from antibiotic de-escalation to faster time to effective therapy.     

Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma

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Novel HLA-A2-restricted human metapneumovirus epitopes reduce viral titers in mice and are recognized by human T cells

Human metapneumovirus (HMPV) is a major cause of morbidity and mortality from acute lower respiratory tract illness, with most individuals seropositive by age five. Despite the presence of neutralizing antibodies, secondary infections are common and can be severe in young, elderly, and immunocompromised persons. Preclinical vaccine studies for HMPV have suggested a need for a balanced antibody and T cell immune response to enhance protection and avoid lung immunopathology. We infected transgenic mice expressing human HLA-A*0201 with HMPV and used ELISPOT to screen overlapping and predicted epitope peptides. We identified six novel HLA-A2 restricted CD8⁺ T cell (T_CD8) epitopes, with M_39–47 (M39) immunodominant. Tetramer staining detected M39-specific T_CD8 in lungs and spleen of HMPV-immune mice. Immunization with adjuvant-formulated M39 peptide reduced lung virus titers upon challenge. Finally, we show that T_CD8 from HLA-A*0201 positive humans recognize M39 by IFNγ ELISPOT and tetramer staining. These results will facilitate HMPV vaccine development and human studies.     

AAV-CRISPR Gene Editing Is Negated by Pre-existing Immunity to Cas9

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“Diabetes care at doorsteps”: A customised mobile van for the prevention,screening, detection and management of diabetes in the urban underprivileged populations of Delhi

Diabetes is on the rise in India and recently shown to be increasing in the urban underprivileged. Lack of awareness of the disease, its complications, combined with lack of financial resources among the underprivileged, often results in late detection and more complications in them. To combat this, healthcare delivered at the doorstep through the use of a customised mobile medical van is a potentially attractive option.We used a customized mobile van (included trained personnel, glucose meters, fundus evaluation camera, apparatus for detection of neuropathy and foot circulation and net enabled Skype calling for remote consultation) for educating general population regarding healthy lifestyle and screening, management and intervention in patients with diabetes.The project covered 10 underprivileged areas (n, 2,31,000 people) in Delhi. Total of 24,072 individuals (10.9% of total population) attended 352 awareness sessions. A total 3,12,347 visits (included repeat visits) were carried out for screening, education and management for obesity and diabetes. During screening (n, 16,834), 2933 subjects (18.7%) had high random blood glucose levels (>200 mg/dL) and had a blood pressure averaging 127.1 ± 23.6/81.3 ± 16.6 mm of mercury (n, 16,339). A pre-post intensive lifestyle counselling for 6 months in a subset of 352 diabetic patients (of which 77.8% i.e. n, 274 were overweight/obese) showed a significant lowering in weight (p < 0.001). In addition, 292 frontline workers and 256 paramedical workers were given training regarding lifestyle and diabetes, over 20 sessions.Based on achievements of this project of spreading awareness, screening, and management of diabetes and obesity in the large number of individuals in urban underprivileged colony, we believe this project could be extended to other cities and rural areas of India, and to other developing countries as well.     

中性粒细胞与淋巴细胞比值对三阴性乳腺癌临床预后及与Ki - 67表达的影响

目的 探讨中性粒细胞与淋巴细胞比值（neutrophil to lymphocyte ratio，NLR）对三阴性乳腺癌的临床预后影响及与Ki - 67表达的关系。方法 回顾性分析2006年1月 - 2012年12月于我院乳腺外科住院治疗的134例三阴性乳腺癌患者。NLR最佳临床分界值采用ROC曲线确定，并依此分NLR＜2.64组和NLR≥2.64组。临床独立预后因素采用单因素和多因素Cox回归模型分析。术后生存时间和生存曲线比较采用Kaplan - Meier和log - rank方法。Ki - 67的表达采用免疫组织化学方法检测。结果 NLR是三阴性乳腺癌的独立预后因素，最佳临界值为2.64。NLR＜2.64组术后中位DFS为39.10月，中位OS为52.30月；NLR≥2.64组术后中位DFS为27.35月，中位OS为37.35月。2组术后DFS和OS比较，差异具有统计学意义（P＜0.05）。NLR低组伴Ki - 67表达阴性的三阴性患者术后中位DFS和OS生存时间显著高于其他情况。结论 NLR是三阴性乳腺癌的关键影响预后因素，具有重复性强、非侵袭性、方便实用等特性，可用于预测三阴性乳腺癌临床预后。     

TACE对原发性肝癌患者的疗效及NLR、PLR的影响研究

目的研究经导管动脉化疗栓塞(TACE)对原发性肝癌患者的疗效及中性粒细胞/淋巴细胞计数比(NLR)、血小板/淋巴细胞计数比(PLR)的影响。方法选择2015年6月～2019年1月我院接诊的原发性肝癌患者80例作为研究对象,采用随机数表法将患者分为两组,每组各40例。对照组予传统肝切除术治疗,观察组采用TACE治疗。对比两组治疗后的临床效果,NLR、PLR、癌胚抗原(CEA)、可溶性B7-H4、可溶性白细胞介素-2受体(sIL-2R)及并发症发生情况。结果治疗后,两组患者的总有效率分别为75.00%和52.50%,观察组高于对照组,差异有统计学意义(P0.05);治疗前,两组患者NLR、PLR水平对比,差异无统计学意义(P0.05);治疗后,患者NLR、PLR水平下降,观察组低于对照组,差异有统计学意义(P0.05);治疗前,两组患者CEA、B7-H4、sIL-2R水平对比,差异无统计学意义(P0.05);治疗后,两组患者CEA、B7-H4、sIL-2R水平下降,观察组低于对照组,差异有统计学意义(P0.05);两组患者并发症发生率分别为17.50%、40.00%,观察组低于对照组,差异有统计学意义(P0.05)。结论在原发性肝癌患者中使用TACE效果显著,可有效改善患者肿瘤标志物水平,减少并发症,值得推广应用。     

Association between Increased Inducible Costimulator/Inducible Costimulator Ligand Expression with Bone Destruction in Apical Periodontitis

IntroductionThe aim was to assess the association of inducible costimulator (ICOS) and ICOS ligand with bone destruction in apical periodontitis (AP).MethodsSpecimens from patients presenting with AP were obtained during apicoectomy and subjected to histopathologic analysis and molecular assessment of ICOS/ICOS ligand. In addition, the experimental AP was induced by exposing the pulp of first mandibular molars of rats. Histologic and radiographic examinations were performed to validate the periapical lesions. The immunolocalization and messenger RNA expression of ICOS/ICOS ligand were evaluated by immunofluorescence staining and quantitative real-time polymerase chain reaction. The osteoclastic activities in periapical lesions, including the lesion size and the expression of tartrate-resistant acid phosphatase and the receptor activator of nuclear factor kappa B ligand, were recorded and followed by correlation analysis with ICOS/ICOS ligand expression.ResultsIn excisional specimens from AP patients, a significantly increased expression of ICOS/ICOS ligand was found compared with the healthy control. In the experimental AP samples, the expression of ICOS/ICOS ligand, tartrate-resistant acid phosphatase, and receptor activator of nuclear factor kappa B ligand was significantly elevated in inflamed periapical tissues (AP group) when compared with the healthy control. The number of ICOS⁺/ICOS ligand⁺ cells was highly correlated with the periapical lesion size (r = 0.892, P < .01 and r = 0.930, P < .01, respectively).ConclusionsThe increased expression of ICOS/ICOS ligand in periapical lesions was associated with the inflammatory infiltration and alveolar bone destruction of AP.