NTRK-Fusions – A new kid on the block

The neurotrophic tyrosine receptor kinases (NTRK) play an important role in the development and function of the nervous system. Fusions involving NTRK and a wide range of genes that act as fusion partners are oncogenic and activate well-known signal transduction pathways like the MAPK-ERK pathway. NTRK fusions occur in many very different tumor entities in children and youth as well as in adults. There are a few tumors like secretory breast cancer and congenital fibrosarcoma for which NTRK fusions are pathognomonic. At the same time there a large number of tumors in which NTRK fusions occur in very rare frequency (e.g., lung cancer). TRK inhibitors offer now the possibility to use NTRK fusion as antitumorigenic targets in a tumor agnostic fashion regardless of the basic histology. It is the task of modern pathology to identify such targetable fusions in a highly effective and efficient manner.     

综合ICU导尿管相关性尿路感染目标性监测数据分析与探讨

目的分析重症监护病房（ICU）导尿管相关性尿路感染目标性监测数据,探讨ICU导尿管相关性尿路感染现状,分析发展趋势,为制订干预措施提供参考。同时,分析现行的导尿管相关性尿路感染（CAUTIs）诊断标准对ICU患者的临床适用性。方法 2012年9月~2013年8月所有收住ICU〉48h的留置导尿患者,进行导尿管相关性尿路感染目标性监测,收集临床资料,计算导尿管使用率及导管相关性感染发病率。结果 2012年9月~2013年8月综合ICU共收住患者357例,留置导尿患者336例;留置时间最长172d,最短2d;共留取386份尿培养标本,细菌培养结果阳性10份,阳性率2.59%;总住院天数2 969d,总留置导尿管日数2 831d,尿道插管使用率95.35%,千日感染率0.353%。结论尿培养结果阳性率与留置导尿管时间长短无相关性;重症监护病房导尿管相关性尿路感染目标性监测有助于规范医疗护理行为,按标准要求进行操作与护理,但使用目前推行的导尿管相关性尿路感染诊断标准（以生物学检查结果为准）会降低感染病例的诊断率,对重症监护病房患者的临床适用性有待进一步考量和验证。     

Comparison of nucleic acid sequence-based amplification and loop-mediated isothermal amplification for diagnosis of human African trypanosomiasis

Diagnosis of human African trypanosomiasis (HAT) using molecular tests should ideally achieve high sensitivity without compromising specificity. This study compared 2 simplified tests, nucleic acid sequence-based amplification (NASBA) combined with oligochromatography (OC) and loop-mediated isothermal amplification (LAMP), executed on 181 blood samples from 65 Trypanosoma brucei gambiense HAT patients, 86 controls, and 30 serological suspects from Uganda. Basing on the composite reference standard, the diagnostic sensitivity and specificity of NASBA were 93.9% (95% confidence interval [CI] = 84.9–98.3%) and 100% (95% CI = 94.9–100%), respectively. The same parameters for LAMP were 76.9% (95% CI = 64.8–86.5%) and 100% (95% CI = 91.6–100%), respectively. The level of agreement between LAMP and microscopy was good with a kappa (κ) value of 79.2% (95% CI = 69.4–88.9%), while that of NASBA-OC/microscopy was very good (κ value 94.6%; 95% CI = 89.3–99.8%). The sensitivity of NASBA-OC was significantly higher than that of LAMP (Z = 2.723; P = 0.007). These tests have potential application to HAT surveillance.     

Reduction in the environmental exposure of pharmaceuticals through diagnostics,Personalised Healthcare and other approaches. A mini review and discussion paper

Pharmaceuticals enter the environment from production, through incorrect disposal as well as from patient use and excretion. Patients’ excretions into wastewater have been judged to form the highest fraction of pharmaceuticals released to the environment. There are concepts and technologies available to address pharmaceuticals emissions from production, incorrect disposal and patient excretion. However, while normal physiological excretion in patients cannot be prevented, there may still be ways to optimise the administration of pharmaceuticals with a view to reducing environmental exposure, while ensuring satisfactory pharmacologically active concentrations in the patient. Towards this goal, state-of-the-art diagnostics emerge as critically important. Describing different approaches for a reduction of environmental exposure, specifically addressing interindividual differences in drug metabolism and personalised healthcare, with recognising antibiotics administration as a related problem, this paper is not strictly speaking a scientific research article but is meant to be more of a compilation of existing and new ideas and a thought-starter.     

Copan WASPLab automation significantly reduces incubation times and allows earlier culture readings

ObjectiveThe aim was to evaluate whether laboratory automation (inoculation and automated incubation combined with timely defined high-resolution digital imaging) may help reduce the time required to obtain reliable culture analysis results.MethodsWe compared the results obtained by WASPLab automation against WASP-based automated inoculation coupled to conventional incubation and manual diagnostic on 1294 clinical samples (483 for the derivation set and 811 for the independent validation set) that included urine, genital tract and non-sterile site specimens, as well as ESwabs for screening of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus aureus (MSSA), extended-spectrum beta-lactamases (ESBLs) and carbapenemase-producing Enterobacteriaceae (CPE). We used sequential routine specimens referred to the bacteriology laboratory at Geneva University Hospitals between October 2018 and March 2019.ResultsThe detection sensitivity of MRSA and MSSA at 18 hr on WASPLab was 100% (95% confidence interval [CI], 94.48–100.00%). The detection sensitivity of ESBL and CPE at 16 hr on WASPLab was 100% (95% confidence interval [CI], 94.87% to 100.00%). For urine specimens, the similarity was 79% (295/375) between 18 hr and 24 hr of incubation on WASPLab. For genital tract and non-sterile site specimens, the similarity between 16 hr and 28 hr of incubation on WASPLab were 26% (72/281) and 77% (123/159) respectively. Thus, 28 hr was defined as the final incubation time on WASPLab for genital tract and non-sterile site specimens.ConclusionsThe results of this study show that WASPLab automation enables a reduction of the culture reading time for all specimens tested without affecting performances. Implementing the established and duly validated incubation times will allow appropriate laboratory workflows for improved efficiency to be built.     

Diagnostic power of VEGF,MMP-9 and TIMP-1 in patients with breast cancer. A multivariate statistical analysis with ROC curve

PurposeVascular endothelial growth factor is an important factor in promoting angiogenesis in malignant processes, matrix metalloproteinase-9 in the degradation of extracellular matrix, which enhances metastasis, and tissue inhibitor of metalloproteinase-1 is its inhibitor. The aim of this study was to investigate the diagnostic power of these parameters in comparison to CA15-3 in breast cancer patients and in relation to the control group.Materials/methodsThe study included 120 breast cancer patients, 60 patients with benign breast tumors and 60 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, CA15-3 by chemiluminescent microparticle immuno assay.ResultsTissue inhibitor of metalloproteinase-1 showed the highest value of sensitivity in breast cancer group (86.25%) and, more importantly, highest value in breast cancer stage I (85%). Vascular endothelial growth factor also showed high sensitivity (stage I and II–75%, III–85%, IV–70% and 76.25% in total breast cancer group) and the highest specificity (85%) from all tested parameters. It was also the only parameter which had statistically significant area under curve in all stages. In the total breast cancer group all tested parameters showed statistically significant area under curve, but the maximum range was obtained for combination: ‘vascular endothelial growth factor + CA15-3′. Vascular endothelial growth factor seems to be the best candidate for diagnosing breast cancer stage I and for differentiating between breast cancer and non-carcinoma cases.ConclusionsThe combined analysis of tested parameters and CA15-3 resulted in an increase in sensitivity and area under curve values, which provides hope for developing new panel of biomarkers that may be used in diagnosing breast cancer in the future.     

The top 100 papers in dry eye – A bibliometric analysis

Purpose

Citation analysis represents one of the best currently available methods for quantifying the impact of articles. Bibliometric studies list the ‘‘best sellers’’ in a single field of interest. The purpose of the present study was to identify and analyze the most frequently cited papers in dry eye research that may be of high interest for researchers and clinicians.