Tailoring antimicrobials in febrile neutropenia: using faster diagnostic and communication tools to improve treatment in the era of extensively resistant pathogens

Febrile Neutropenia represents a medical emergency and the use of appropriate antimicrobial therapy is essential for a better outcome. Although being time-consuming, conventional cultures and antimicrobial susceptibility tests remain the golden standard practices for microbiology identification. Final reports are typically available within several days. Faster diagnostic tools, such as species identification trough Matrix Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF) and molecular techniques might help to shorten time to diagnostic and also guide definitive therapy in this scenario. Here we present a case in which the use of a diagnostic molecular workflow combining MALDI-TOF and real-time PCR for relevant genes codifying antibiotic resistant integrated with instant communication report, led to a tailored and more appropriate treatment in a patient presenting with febrile neutropenia.     

Targeted therapies forpatients withadvanced NSCLC harboring wild-type EGFR：what’s new andwhat’s enough

Historically, non?small cell lung cancer (NSCLC) is divided into squamous and nonsquamous subtypes based on histo?logic features. With a growing number of oncogenic drivers being identiifed in squamous...     

Risk of defeats in the central nervous system during deep space missions

Space flight factors (SFF) significantly affect the operating activity of astronauts during deep space missions. Gravitational overloads, hypo-magnetic field and ionizing radiation are the main SFF that perturb the normal activity of the central nervous system (CNS). Acute and chronic CNS risks include alterations in cognitive abilities, reduction of motor functions and behavioural changes. Multiple experimental works have been devoted to the SFF effects on integrative functional activity of the brain; however, the model parameters utilized have not always been ideal and consistent. Even less is known regarding the combined effects of these SFF in a real interplanetary mission, for example to Mars. Our review aims to systemize and analyse the last advancements in astrobiology, with a focus on the combined effects of SFF; as well as to discuss on unification of the parameters for ground-based models of deep space missions.     

Pathology of pancreatic ductal adenocarcinoma: Facts,challenges and future developments

Despite major improvements concerning its diagnosis and treatment, pancreatic ductal adenocarcinoma (PDAC) remains an aggressive disease with an extremely poor prognosis. Pathology, as interface discipline between basic and clinical medicine, has substantially contributed to the recent developments and has laid the basis for further progress. The definition and classification of precursor lesions of PDAC and their molecular characterization is a fundamental step for the potential identification of biomarkers and the development of imaging methods for early detection. In addition, by integrating findings in humans with the knowledge acquired through the investigation of transgenic mouse models for PDAC, a new model for pancreatic carcinogenesis has been proposed and partially validated in individuals with genetic predisposition for PDAC. The introduction and validation of a standardized system for pathology reporting based on the axial slicing technique has shown that most pancreatic cancer resections are R1 resections and that this is due to inherent anatomical and biological properties of PDAC. This standardized assessment of prognostic relevant parameters represents the basis for the successful conduction of multicentric studies and for the interpretation of their results. Finally, recent studies have shown that distinct molecular subtypes of PDAC exist and are associated with different prognosis and therapy response. The prospective validation of these results and the integration of molecular analyses in a comprehensive pathology report in the context of individualised cancer therapy represent a major challenge for the future.     

人结直肠锯齿状腺癌的研究现状

结直肠锯齿状腺癌（serrated adenocarcinoma，SAC）作为大肠癌的一种特殊临床类型，因其癌变途径的特殊性，检测以及较差的治疗反应和预后逐渐引起众多研究者的兴趣。其产生的途径主要为“锯齿状通路”途径，锯齿状通路途径以BRAF突变、微卫星体不稳定（microsatellite instability，MSI））和CpG岛的甲基化（CpG island methylator phenotype，CIMP）为特征。由于特殊的形态和内镜特征及特殊的发生部位，在结肠镜检查时很容易漏诊，甚至病理评估时也极易被忽视，临床确诊时往往已处于进展期，患者预后差，生存率低。本文针对锯齿状结直肠腺癌流行病学、危险因素、临床特征、病理学特征、分子特征等作一综述。     

Thrombotic microangiopathic hemolytic anemia in systemic lupus erythematosus associated with antiphospholipid antibodies: usefulness of monitoring coagulation–fibrinolysis markers

Abstract

We report on a 24-year-old woman with systemic lupus erythematosus and lupus anticoagulant who developed chronic thrombotic microangiopathic hemolytic anemia. The patient responded well to a combination of plasma exchange and anticoagulant therapy. Changes in the molecular markers for coagulation and fibrinolysis corresponded with the disease activity. We suggest that thrombotic microangiopathic hemolytic anemia should be suspected when anemia and thrombocytopenia of unknown etiologies occur in systemic lupus erythematosus. In such cases, the evaluation of molecular markers for coagulation and fibrinolysis might be helpful both for diagnosis and for assessing the response to therapy.     

Comparison of morphological and molecular genetic sex-typing on mediaeval human skeletal remains

Archaeological excavations conducted at an early mediaeval cemetery in Volders (Tyrol, Austria) produced 141 complete skeletal remains dated between the 5th/6th and 12th/13th centuries. These skeletons represent one of the largest historical series of human remains ever discovered in the East Alpine region. Little historical information is available for this region and time period. The good state of preservation of these bioarchaeological finds offered the opportunity of performing molecular genetic investigations. Adequate DNA extraction methods were tested in the attempt to obtain as high DNA yields as possible for further analyses. Molecular genetic sex-typing using a dedicated PCR multiplex (“Genderplex”) gave interpretable results in 88 remains, 78 of which had previously been sexed based on morphological features. We observed a discrepancy in sex determination between the two methods in 21 cases. An unbiased follow-up morphological examination of these finds showed congruence with the DNA results in all but five samples.