Clostridium difficile assoziierter Durchfall: "An emerging infection"

Zusammenfassung: Die Clostridium difficile assoziierte Diarrhö (CDAD) wird häufig als lästige und relativ banale Nebenwirkung einer Antibiotikatherapie angesehen. Während schon in den 1980er und 90er Jahren Morbidität, Mortalität und entsprechend auch die Kosten von CDAD beträchtlich waren, sind diese aufgrund des Aufkommens eines hochvirulenten Stamms von Clostridium difficile (C.difficile) Anfang2000 deutlich angestiegen. Die pathogenetischen Schlüsselereignisse sind Veränderungen der Darmflora nach Antibiotikagabe, Kolonisation mit einem toxinbildenden C.difficile und dessen intraluminale Vermehrung. Die Therapie besteht bei milden Formen im Absetzen der angeschuldigten Medikamente, bei mäßig bis schwer ausgeprägten Erkrankungen erfolgt die Gabe von Metronidazol oder Vancomycin per os. Als ultima ratio bei toxischem Megakolon muss die subtotale Hemikolektomie erwogen werden. Der verantwortungsvolle Einsatz von Antibiotika ("antibiotic stewardship") in Kombination mit spitalhygienischen Maßnahmen sind essenziell, um Ausbrüchen vorzubeugen und sie einzudämme

Genetic divergence in the cave cricket Troglophilus neglectus (Orthoptera Rhaphidophoridae): mitochondrial and nuclear DNA data.

In this study we used sequence polymorphisms at one mitochondrial and one nuclear gene (Cytochrome Oxidase subunit I and Internal Transcribed Spacer 1, respectively) to assess the degree of genetic divergence among 21 populations of the cave cricket Troglophilus neglectus (Orthoptera, Rhaphidophoridae), a species whose currently known range extends from the Balkan Peninsula to Southern Bavaria. Nineteen populations were sampled in Northern Italy, Slovenia, Croatia and Bosnia and Herzegovina, while two populations came from Germany (Lower Saxony) and Czech Republic, thus well outside the species range. Molecular data revealed a high level of fragmentation, with most of the study populations bearing exclusive haplotypes, the sole exception being the German and Czech specimens, which carried haplotypes also occurring at Slovenian locations. Spatial distribution of genetic heterogeneity and pattern of genetic divergence argue in favor of a recent origin of the two Central European populations, possibly through man-mediated dispersal event(s). These populations being not considered, our data are in remarkable agreement with a previous study based on allozymes conducted on a subset of populations of the same species and, more generally, with what is known on the population genetics of peri-Mediterranean Rhaphidophorids

Dolichopoda cave crickets from Peloponnese (Orthoptera, Rhaphidophoridae): molecular and morphological investigations reveal four new species for Greece

Three species belonging to the genus Dolichopoda (Orthoptera; Rhaphidopohoridae) are known so far from the Peloponnese, all endemic to the area. In particular, D. matsakisi is known from two mountains in the North, while D. dalensi is present in the east region. The third species, D. unicolor, is distributed in the southern part of the Peloponnese, inhabiting caves on Mt Taygetos and Mani Peninsula. Recently, extensive sampling work in most of the Peloponnese has led to the discovery of new taxa, morphologically differentiated by the above three known species. To investigate the delimitation of the Peloponnesian species of Dolichopoda, we performed both morphological and molecular analyses. Morphological analysis was carried out by considering diagnostic characters generally used to distinguish different taxa, as the shape of epiphallus in males and the subgenital plate in females. Molecular analysis was performed by sequencing three mitochondrial genes, 12S rRNA, 16S rRNA, and COI, and one nuclear gene, 28S rRNA. Results from both morphological and molecular analyses were used to revise the taxonomic arrangement of the Peloponnesian species. On the whole, we were able to distinguish seven lineages of Peloponnesian Dolichopoda species, of which D. kofinasi n.sp., D.epidavrii n.sp., D. poseidonica n.sp., and D. propanti n.sp. are described as new species

Integrated waveguides and deterministically positioned nitrogen vacancy centers in diamond created by femtosecond laser writing

Diamond's nitrogen vacancy (NV) center is an optically active defect with long spin coherence times, showing great potential for both efficient nanoscale magnetometry and quantum information processing schemes. Recently, both the formation of buried 3D optical waveguides and high quality single NVs in diamond were demonstrated using the versatile femtosecond laser-writing technique. However, until now, combining these technologies has been an outstanding challenge. In this work, we fabricate laser written photonic waveguides in quantum grade diamond which are aligned to within micron resolution to single laser-written NVs, enabling an integrated platform providing deterministically positioned waveguide-coupled NVs. This fabrication technology opens the way towards on-chip optical routing of single photons between NVs and optically integrated spin-based sensing

Broad-Range 16S rRNA Gene Polymerase Chain Reaction for Diagnosis of Culture-Negative Bacterial Infections

This study defines the role of 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR) for diagnosis of culture-negative bacterial infections. Our data show that 16S rRNA PCR is particularly valuable for identification of pathogens in patients pretreated with antibiotic

Breast Cancer Following Hodgkin's Disease

The advent of effective chemo-radiotherapy has made Hodgkin Disease (HD) a highly curable malignancy, but the great improvement in survival rates allowed the observation in long-term survivors of several treatment complications. Secondary malignancies are the most serious complications and breast cancer (BC) represents the most common solid tumor among female survivors. The aim of our analysis is to describe the clinico-pathological characteristics and management of BC occurred after HD treatment. Between 1960 and 2003, 2,039 patients were treated for HD at the Department of Radiotherapy-Oncology of the Florence University. In this study we considered 1,538 patients on whom a minimum follow up of 6 months had been obtained. Of these, 725 were women. The most represented histological subtype was nodular sclerosis (50.6%). Supradiaphragmatic alone or with subdiaphragmatic complementary extended field radiotherapy was delivered to 83.1% of patients while supradiaphragmatic involved field radiotherapy was delivered to 10.7% of patients. Concerning the characteristics and incidence of BC, we focused our analysis exclusively on the female group. We found that BC occurred in 39, with an overall incidence of 5.4%. The mean interval after Hodgkin treatment was 19.5 years (SD +/- 9.0). The median age of BC diagnosis was 50.8 years (SD +/- 13.3) while the median age of Hodgkin diagnosis was 31.2 years (SD +/- 14.5). Thirty-seven women received mediastinal irradiation. We observed a decreasing trend of the secondary BC incidence with increasing age of Hodgkin treatment with the maximum incidence registered in women treated at age 20 or younger. In Our Institute we perform a whole life follow up and recommend that annual mammography begins 10 years after HD treatment or, in any case, not later than age 40

Cardiovascular Reasons for Access to a Tertiary Oncological Emergency Service: The CARILLON Study

Background: The prevalence of acute cardiovascular diseases (CVDs) in cancer patients is steadily increasing and represents a significant reason for admission to the emergency department (ED). Methods: We conducted a prospective observational study, enrolling consecutive patients with cancer presenting to a tertiary oncological ED and consequently admitted to the oncology ward. Two groups of patients were identified based on main symptoms that lead to ED presentation: symptoms potentially related to CVD vs. symptoms potentially not related to CVD. The aims of the study were to describe the prevalence of symptoms potentially related to CVD in this specific setting and to evaluate the prevalence of definite CV diagnoses at discharge. Secondary endpoints were new intercurrent in-hospital CV events occurrence, length of stay in the oncology ward, and mid-term mortality for all-cause. Results: A total of 469 patients (51.8% female, median age 68.0 [59.1–76.3]) were enrolled. One hundred and eighty-six out of 469 (39.7%) presented to the ED with symptoms potentially related to CVD. Baseline characteristics were substantially similar between the two study groups. A discharge diagnosis of CVD was confirmed in 24/186 (12.9%) patients presenting with symptoms potentially related to CVD and in no patients presenting without symptoms potentially related to CVD (p < 0.01). During a median follow-up of 3.4 (1.2–6.5) months, 204 (43.5%) patients died (incidence rate of 10.1 per 100 person/months). No differences were found between study groups in terms of all-cause mortality (hazard ratio [HR]: 0.85, 95% confidence interval [CI] 0.64–1.12), new in-hospital CV events (HR: 1.03, 95% CI 0.77–1.37), and length of stay (p = 0.57). Conclusions: In a contemporary cohort of cancer patients presenting to a tertiary oncological ED and admitted to an oncology ward, symptoms potentially related to CVD were present in around 40% of patients, but only a minority were actually diagnosed with an acute CVD

Digital biomarker-based individualized prognosis for people at risk of dementia

Background: Research investigating treatments and interventions for cognitive decline fail due to difficulties in accurately recognizing behavioral signatures in the presymptomatic stages of the disease. For this validation study, we took our previously constructed digital biomarker-based prognostic models and focused on generalizability and robustness of the models. Method: We validated prognostic models characterizing subjects using digital biomarkers in a longitudinal, multi-site, 40-month prospective study collecting data in memory clinics, general practitioner offices, and home environments. Results: Our models were able to accurately discriminate between healthy subjects and individuals at risk to progress to dementia within 3 years. The model was also able to differentiate between people with or without amyloid neuropathology and classify fast and slow cognitive decliners with a very good diagnostic performance. Conclusion: Digital biomarker prognostic models can be a useful tool to assist large-scale population screening for the early detection of cognitive impairment and patient monitoring over time

Prognostic value of preoperative von Willebrand factor plasma levels in patients with Glioblastoma

Circulating biomarker for malignant gliomas could improve both differential diagnosis and clinical management of brain tumor patients. Among all gliomas, glioblastoma (GBM) is considered the most hypervascularized tumor with activation of multiple proangiogenic signaling pathways that enhance tumor growth. To investigate whether preoperative antigen plasma level of von Willebrand Factor (VWF:Ag) might be possible marker for GBM onset, progression, and prognosis, we retrospectively examined 57 patients with histological diagnosis for GBM and 23 meningiomas (MNGs), benign intracranial expansive lesions, enrolled as controls. Blood samples were collected from all the patients before tumor resection. Plasma von Willebrand Factor (VWF):Ag levels were determined by using a latex particle-enhanced immunoturbidimetric assay. The median levels of vWF:Ag were significantly higher in GBMs than in meningiomas (MNGs) (183 vs. 133IU/dL, P=0.01). The cumulative 1-year survival was significantly shorter in patients with VWF:Ag levels 200IU/dL than in those with levels <200IU/dL and increased VWF levels were associated with a threefold higher risk of death in GBM patients. Our data suggest that VWF:Ag could be a circulating biomarker of disease malignancy, that could be considered, in association with other genetic and epigenetic factors, currently available in the GBM management. Future studies should investigate whether plasma VWF:Ag levels could also be used to monitor therapeutic effects and whether it may have a prognostic value

The oncofetal protein IMP3: a novel grading tool and predictor of poor clinical outcome in human gliomas

Morphologic criteria illustrated in WHO guidelines are the most significant prognostic factor in human gliomas, but novel biomarkers are needed to identify patients with a poorer outcome. The present study examined the expression of the oncofetal protein IMP3 in a series of 135 patients affected by high-grade (grade III and IV) gliomas, correlating the results with proliferative activity, molecular parameters, and clinical and follow-up data. Overall, IMP3 expression was higher in glioblastomas (68%) than in grade III tumors (20%, P < 0.0001), and IMP3-positive high-grade gliomas showed a shorter overall and disease-free survival than negative ones (P = 0.0002 and P = 0.006, resp.). IMP3 expression was significantly associated with the absence of mutations of IDH1 gene (P = 0.0001) and with the unmethylated phenotype of MGMT in high-grade gliomas (P = 0.004). High Ki67 levels were correlated with better prognosis in glioblastomas but IMP3 expression was not correlated with the proliferation index. These findings confirm the role of IMP3 as a marker of poor outcome, also in consideration of its association with IDH1 wild-type phenotype and MGMT unmethylated status. The data suggest that IMP3 staining could identify a subgroup of patients with poor prognosis and at risk of recurrence in high-grade gliomas