Epidemic Spread of a Single Clone of Methicillin-Resistant Staphylococcus aureus among Injection Drug Users in Zurich, Switzerland

We describe an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) among injection drug users (IDUs). From August 1994 through December 1999, we registered 31 IDUs with MRSA infections (12 with soft-tissue infection, 7 with pneumonia [fatal in 1], 7 with endocarditis [fatal in 1], 2 with osteomyelitis, 2 with septic arthritis, and 1 with ulcerative tonsillitis), with a marked increase in the number of IDUs registered during 1998 and 1999. Of 31 patients, 15 (48%) were infected with human immunodeficiency virus. A point-prevalence study among IDUs who frequented outpatient facilities in Zurich revealed an MRSA carriage rate of 10.3% (range, 0%-28.6%) in various facilities. In all but 1 case, pulsed-field gel electrophoresis banding patterns of isolates obtained from these patients were indistinguishable from isolates of the initial 31 IDUs registered. Risk factors for MRSA carriage were disability and prior hospitalization in a hospice. In summary, MRSA became endemic in IDUs in Zurich as a result of the spread of a single clone. This clone caused major morbidity and was responsible for a lethal outcome in 2 case

Application of light shelves in a refurbished student dormitory: Energy, lightings and comfort aspects

The transparent elements of the building envelope have a crucial role not only in term of heat and mass transfers control, but also for natural light penetration, sound insulation, thermal and visual comfort of the occupants and their health. Among passive technologies, the light shelves could be architectural solutions for improving daylight penetration and for controlling thermal loads. The available research papers usually focus on one aspect. For this reason, the aim of the present study is to analyse the application of the light shelves with multidisciplinary approach and thus, taking into account: daylight, electricity for lighting, cooling and heating needs and thermo-hygrometric comfort. The case study is a real dormitory building placed in Athens and subject to a deep energy renovation toward the nearly zero energy building target. EnergyPlus, by means of DesignBuilder interface, has been used as dynamic simulation tool. Among ten different configurations, the optimal one turns out to be the internal horizontal light shelf placed at 50 cm from the top of the window with a depth of 90 cm or 60 cm. It has been found that in some cases the reduction of electricity for lighting cannot balance the variation in heating and cooling needs

Multi-disciplinary analysis of light shelves application within a student dormitory refurbishment

The achievement of sustainable cities and communities is closely linked to an accurate design of the buildings. In this context, the transparent elements of the building envelope have a crucial role since, on one hand, they are a bottleneck in regards to heat and mass transfers and sound propagation, while, on the other hand, they must allow daylight penetration. Thus, they are responsible for occupants' thermal and visual comfort and their health. Considering passive solutions for windows, the light shelves can improve natural light penetration, reducing the lights' electricity demand and controlling windows' related thermal aspects. The scientific literature is characterized by several studies that analyze this topic, which, however, focus only on the daylight field and sometimes the energy saving for lights. Moreover, they often refer to fixed sky type for the simulations. The aim of the present study is to analyze the application of the light shelves with a multi-disciplinary approach, by means of dynamic simulations, in the EnergyPlus engine, for a whole year. A new methodological approach is presented in order to investigate the technology under different fields of interest: daylight, lighting energy, cooling and heating needs, and thermo-hygrometric comfort. The case study chosen is an existing building, a student dormitory belonging to the University of Athens. It is subject to a deep energy renovation to conform to the "nearly Zero Energy Building" target, in the frame of a European research project called Pro-GET-onE (G.A No. 723747). By means of the calibrated numerical model of this HVAC-building system, ten different configurations of light shelves have been investigated. The best solution is given by the application of an internal horizontal light shelf placed at 50 cm from the top of the window with a depth of 90 or 60 cm. It has been found that despite the reduction in electricity demand for lighting, the variation in heating and cooling needs does not always lead to a benefit

Neuroendocrine neoplasms of the esophagus and stomach.

Esophageal neuroendocrine neoplasms (E-NENs) are much rarer than other gastro-entero-pancreatic neuroendocrine neoplasms, the majority showing aggressive behavior with early dissemination and poor prognosis. Among E-NENs, exceptionally rare well differentiated neuroendocrine tumors (E-NET) and more frequent esophageal poorly differentiated neuroendocrine carcinomas (E-NEC) and mixed neuroendocrine-non neuroendocrine neoplasms (MiNEN) can be recognized. E-NECs usually exhibit a small cell morphology or mixed small and large cells. Esophageal MiNEN are composed of NEC component admixed with adenocarcinoma or squamous cell carcinoma. Gastric (G) NENs encompass a wide spectrum of entities ranging from indolent G-NETs to highly aggressive G-NECs and MiNENs. Among G-NETs, ECL-cell NETs are the most common and, although composed of histamine-producing cells, are a heterogeneous group of neoplastic proliferations showing different clinical and prognostic features depending on the patient's clinico-pathological background including the morphology of the peri-tumoral mucosa, gastrin serum levels, presence or absence of antral G-cell hyperplasia, and presence or absence of MEN1 syndrome. In general, NET associated with hypergastrinemia show a better outcome than NET not associated with hypergastrinemia. G-NECs and MiNENs are aggressive neoplasms more frequently observed in males and associated with a dismal prognosis

Knowledge translation in challenging healthcare environments: The PIOPPO experience at the National Centre of Oncological Hadrontherapy (CNAO Foundation).

Knowledge translation is the ability to translate concepts and ideas effectively among different stakeholders, leading to innovation and new knowledge. Translating knowledge is particularly challenging in the healthcare sector, which has been experiencing a shift from a centralized and sequential model of value creation to a more distributed and open model, where various stakeholders (including patients) act as co-creators of the outcome. According to management as well as the medical literature, knowledge translation in healthcare has been mainly seen as the translation of scientific research into clinical practice. However, different types of knowledge translation emerge, such as when multidisciplinary teams need to work together on a joint medical project. In this situation, multiple backgrounds, competencies, skills, and emotional feelings of the different stakeholders are a compelling barrier that prevents the effective transfer and sharing of knowledge. This is why knowledge translation needs a set of enablers to facilitate the transfer, sharing, and creation of new knowledge, innovation, and ideas. This paper investigates such a perspective by analyzing the PIOPPO project from the National Centre of Oncological Hadrontherapy (CNAO Foundation) in Pavia, Italy. The CNAO is one of the few dual-beam Hadrontherapy centres in the world that provides a beam that is able to irradiate patients with protons or carbon ions to treat radioresistant tumours. The PIOPPO project is an experimental phase 2 trial involving preoperative chemotherapy and carbon ion therapy to treat resectable and borderline-resectable pancreatic adenocarcinoma. The stakeholders involved in the PIOPPO trial have different characteristics, both in terms of competencies and emotions. The PIOPPO multidisciplinary team includes highly skilled professionals from several disciplines, which are not all related to medicine (from oncologists to physicists, from biologists to surgeons). Pancreatic cancer patients are also involved while experiencing a challenging personal time. The paper analyses the knowledge translation flows, instruments, and issues among such different stakeholders

Simultaneous PET-MRI Studies of the Concordance of Atrophy and Hypometabolism in Syndromic Variants of Alzheimer's Disease and Frontotemporal Dementia: An Extended Case Series

Background: Simultaneous PET-MRI is used to compare patterns of cerebral hypometabolism and atrophy in six different dementia syndromes. Objectives: The primary objective was to conduct an initial exploratory study regarding the concordance of atrophy and hypometabolism in syndromic variants of Alzheimer’s disease (AD) and frontotemporal dementia (FTD). The secondary objective was to determine the effect of image analysis methods on determination of atrophy and hypometabolism. Method: PET and MRI data were acquired simultaneously on 24 subjects with six variants of AD and FTD (n = 4 per group). Atrophy was rated visually and also quantified with measures of cortical thickness. Hypometabolism was rated visually and also quantified using atlas- and SPM-based approaches. Concordance was measured using weighted Cohen’s kappa. Results: Atrophy-hypometabolism concordance differed markedly between patient groups; kappa scores ranged from 0.13 (nonfluent/agrammatic variant of primary progressive aphasia, nfvPPA) to 0.49 (posterior cortical variant of AD, PCA). Heterogeneity was also observed within groups; the confidence intervals of kappa scores ranging from 0–0.25 for PCA to 0.29–0.61 for nfvPPA. More widespread MRI and PET changes were identified using quantitative methods than on visual rating. Conclusion: The marked differences in concordance identified in this initial study may reflect differences in the molecular pathologies underlying AD and FTD syndromic variants but also operational differences in the methods used to diagnose these syndromes. The superior ability of quantitative methodologies to detect changes on PET and MRI, if confirmed on larger cohorts, may favor their usage over qualitative visual inspection in future clinical diagnostic practic

Autonomic pain responses during sleep: a study of heart rate variability

The autonomic nervous system (ANS) reacts to nociceptive stimulation during sleep, but whether this reaction is contingent to cortical arousal, and whether one of the autonomic arms (sympathetic/parasympathetic) predominates over the other remains unknown. We assessed ANS reactivity to nociceptive stimulation during all sleep stages through heart rate variability, and correlated the results with the presence of cortical arousal measured in concomitant 32-channel EEG. Fourteen healthy volunteers underwent whole-night polysomnography during which nociceptive laser stimuli were applied over the hand. RR intervals (RR) and spectral analysis by wavelet transform were performed to assess parasympathetic (HF(WV)) and sympathetic (LF(WV) and LF(WV)/HF(WV) ratio) reactivity. During all sleep stages, RR significantly decreased in reaction to nociceptive stimulations, reaching a level similar to that of wakefulness, at the 3rd beat post-stimulus and returning to baseline after seven beats. This RR decrease was associated with an increase in sympathetic LF(WV) and LF(WV)/HF(WV) ratio without any parasympathetic HF(WV) change. Albeit RR decrease existed even in the absence of arousals, it was significantly higher when an arousal followed the noxious stimulus. These results suggest that the sympathetic-dependent cardiac activation induced by nociceptive stimuli is modulated by a sleep dependent phenomenon related to cortical activation and not by sleep itself, since it reaches a same intensity whatever the state of vigilance

Re-irradiation with carbon ion radiotherapy for pelvic rectal cancer recurrences in patients previously irradiated to the pelvis

Background/Aim: Re-irradiation of locally recurrent rectal cancer poses challenges due to the proximity of critical organs, such as the bowel. This study aimed at evaluating the safety and efficacy of re-irradiation with Carbon Ion Radiotherapy (CIRT) in rectal cancer patients with local recurrence. Patients and Methods: Between 2014 and 2018, 14 patients were treated at the National Center of Oncological Hadrontherapy (CNAO Foundation) with CIRT for locally recurrent rectal cancer. Results: All patients concluded the treatment. No G≥3 acute/late reaction nor pelvic infections were observed. The 1-year and 2-year local control rates were, 78% and 52%, respectively, and relapse occurred close to the bowel in 6 patients. The 1-year and 2-year overall survival rates were 100% and 76.2% each; while the 1-year and 2-year metastasis free survival rates were 64.3% and 43%. Conclusion: CIRT as re-irradiation for locally recurrent rectal cancer emerges as a safe and valid treatment with an acceptable rate of morbidity of surrounding healthy tissue

Loss of Primary Cilia Potentiates BRAF/MAPK Pathway Activation in Rhabdoid Colorectal Carcinoma: A Series of 21 Cases Showing Ciliary Rootlet CoiledCoil (CROCC) Alterations

A rhabdoid colorectal tumor (RCT) is a rare cancer with aggressive clinical behavior. Recently, it has been recognized as a distinct disease entity, characterized by genetic alterations in the SMARCB1 and Ciliary Rootlet Coiled-Coil (CROCC). We here investigate the genetic and immunophenotypic profiling of 21 RCTs using immunohistochemistry and next-generation sequencing. Mismatch repair-deficient phenotypes were identified in 60% of RCTs. Similarly, a large proportion of cancers exhibited the combined marker phenotype (CK7-/CK20-/CDX2-) not common to classical adenocarcinoma variants. More than 70% of cases displayed aberrant activation of the mitogen-activated protein kinase (MAPK) pathway with mutations prevalently in BRAF V600E. SMARCB1/INI1 expression was normal in a large majority of lesions. In contrast, ciliogenic markers including CROCC and γ-tubulin were globally altered in tumors. Notably, CROCC and γ-tubulin were observed to colocalize in large cilia found on cancer tissues but not in normal controls. Taken together, our findings indicate that primary ciliogenesis and MAPK pathway activation contribute to the aggressiveness of RCTs and, therefore, may constitute a novel therapeutic target

BRAF Rearrangements and BRAF V600E Mutations Are Seen in a Subset of Pancreatic Carcinomas With Acinar Differentiation.

Comprehensive genomic profiling has demonstrated that approximately 20% of pancreatic carcinomas with acinar differentiation harbor potentially targetable BRAF fusions that activate the MAPK pathway. To validate the above finding by BRAF break-apart fluorescence in situ hybridization (FISH) in a large series of pure acinar cell carcinomas (ACCs), evaluate tumors for the presence of BRAF V600E mutations, and compare clinicopathologic features of tumors with BRAF rearrangements with those without. Thirty cases of pure ACC and 6 cases of mixed acinar-neuroendocrine carcinoma (ACC-NEC) were retrieved. A break-apart FISH probe was used to detect BRAF rearrangements. Immunohistochemistry for BRAF V600E was performed. BRAF rearrangements by FISH were found in 6 of 36 cases (17%), 5 of which were pure ACC and 1 was a mixed ACC-NEC. Follow-up was available in 29 of 36 (81%). The median survival was 22 months for BRAF-rearranged cases and 16 months for BRAF-intact cases; the 2-year overall survival was 50% for BRAF-rearranged cases and 35% for BRAF-intact cases. No significant clinicopathologic differences were identified in cases with BRAF rearrangement compared with those without BRAF rearrangement. BRAF V600E mutation was identified in 2 of 34 cases (6%), both of which were pure ACC and were BRAF-intact by FISH. This study supports the finding that BRAF rearrangements are present in approximately 20% of cases and identified BRAF V600E mutations in approximately 5% of cases. These cases may benefit from targeted therapy