Extranodal Lymphoproliferative Processes and Flow Cytometry

Objective: Fine-needle aspiration (FNA) cytology is a safe and cost-effective technique for the diagnosis of lymphoproliferative processes, especially when correlated with clinical and imaging studies. However, cytology alone may be unable to detect a lymphoid neoplastic process, as architectural features are less obvious than in histologic preparations and, in certain cases, reactive processes may mimic lymphoma. Flow cytometry (FC) has been recognized as an important ancillary technique in the diagnosis of lymphoid neoplasms and it can be used in conjunction with FNA in the evaluation of lymphoproliferative processes. Study Design: We performed a review of the published literature concerning FC applied to the detection of salivary glands and thyroid lymphoproliferative processes, which are frequently related to autoimmune diseases and difficult to diagnose by cytomorphology alone. Results: FC is able to detect and subtype non-Hodgkin lymphomas and may contribute to the exclusion of a neoplastic process in cytologically unclear cases. Conclusions: FC can be successfully applied in the differential diagnosis of lymphoproliferative processes in the head and neck region. The FNA-FC combined approach can reduce time to therapy and may prevent unnecessary surgical biopsies

Supramolecular spectrally encoded microgels with double strand probes for absolute and direct miRNA fluorescence detection at high sensitivity

We present novel microgels as a particle-based suspension array for direct and absolute microRNA (miRNA) detection. The microgels feature a flexible molecular architecture, antifouling properties, and enhanced sensitivity with a large dynamic range of detection. Specifically, they possess a core-shell molecular architecture with two different fluorescent dyes for multiplex spectral analyses and are endowed with a fluorescent probe for miRNA detection. Encoding and detection fluorescence signals are distinguishable by nonoverlapping emission spectra. Tunable fluorescence probe conjugation and emission confinement on single microgels allow for ultrasensitive miRNA detection. Indeed, the suspension array has high selectivity and sensitivity with absolute quantification, a detection limit of 10(-15) M, a dynamic range from 10(-9) to 10(-15) M, and higher accuracy than qRT-PCR. The antifouling properties of the microgels also permit the direct measurement of miRNAs in serum, without sample pretreatment or target amplification. A multiplexed assay has been tested for a set of miRNAs chosen as cancer biomarkers

Building energy modelling and monitoring by integration of IoT devices and Building Information Models

In recent years, the research about energy waste and CO2 emission reduction has gained a strong momentum, also pushed by European and national funding initiatives. The main purpose of this large effort is to reduce the effects of greenhouse emission, climate change to head for a sustainable society. In this scenario, Information and Communication Technologies (ICT) play a key role. From one side, advances in physical and environmental information sensing, communication and processing, enabled the monitoring of energy behaviour of buildings in real-time. The access to this information has been made easy and ubiquitous thank to Internet-of-Things (IoT) devices and protocols. From the other side, the creation of digital repositories of buildings and districts (i.e. Building Information Models - BIM) enabled the development of complex and rich energy models that can be used for simulation and prediction purposes. As such, an opportunity is emerging of mixing these two information categories to either create better models and to detect unwanted or inefficient energy behaviours. In this paper, we present a software architecture for management and simulation of energy behaviours in buildings that integrates heterogeneous data such as BIM, IoT, GIS (Geographical Information System) and meteorological services. This integration allows: i) (near-) real-time visualisation of energy consumption information in the building context and ii) building performance evaluation through energy modelling and simulation exploiting data from the field and real weather conditions. Finally, we discuss the experimental results obtained in a real-world case-study

Indoor Air-Temperature Forecast for Energy-Efficient Management in Smart Buildings

In the last few years, the reduction of energy consumption and pollution became mandatory. It became also a common goal of many countries. Only in Europe, the building sector is responsible for the total 40% of energy consumption and 36% of CO2 pollution. Therefore, new control policies based on the forecast of buildings energy behaviors can be developed to reduce energy waste (i.e. policies for Demand Response and Demand Side Management). This paper discusses an innovative methodology for smart building indoor air-temperature forecasting. This methodology is based on a Non-linear Autoregressive neural network. This neural network has been trained and validated with a dataset consisting of six years indoor air-temperature values of a building demonstrator. In detail, we have studied three characterizing rooms and the whole building. Experimental results of energy prediction are presented and discussed

Positive end expiratory pressure in acute hypoxemic respiratory failure due to community acquired pneumonia: Do we need a personalized approach?

Background. Acute respiratory failure (ARF) is a life-threatening complication in patients with community acquired pneumonia (CAP). The use of non-invasive ventilation is controversial. With this prospective, observational study we aimed to describe a protocol to assess whether a patient with moderate-to-severe hypoxemic ARF secondary to CAP benefits, in clinical and laboratoristic terms, from the application of a positive end expiratory pressure (PEEP) + oxygen vs oxygen alone. Methods. Patients who benefit from PEEP application (PEEP-responders) were defined as those with partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) increase > 20% and/or reduction of respiratory distress during PEEP + oxygen therapy compared to oxygen therapy alone. Clinical characteristics and outcomes were compared between PEEP-responders and PEEP-non responders. Results. Out of 41 patients, 27 (66%) benefit from PEEP application (PEEPresponders), the best response was obtained with a PEEP of 10 cmH2O in 13 patients, 7.5 cmH2O in eight and 5 cmH2O in six. PEEP-responders were less likely to present comorbidities compared to PEEP-non responders. No differences between groups were found in regards to endotracheal intubation criteria fullfillment, intensive care unit admission and in-hospital mortality, while PEEP-responders had a shorter length of hospital stay. Discussion. The application of a protocol to evaluate PEEP responsiveness might be useful in patients with moderate-to-severe hypoxemic ARF due to CAP in order to personalize and maximize the effectiveness of therapy, and prevent the inappropriate PEEP use. PEEP responsiveness does not seem to be associated with better outcomes, with the exception of a shorter length of hospital stay

The immune cell landscape of metastatic uveal melanoma correlates with overall survival

Uveal melanoma (UM) represents the most common primary intra-ocular malignancy in adults. Up to 50% of the patients develop distant metastases within 10\u2009years from diagnosis, with the liver as the most common site. Upon metastatization, life expectancy strongly reduces and immune checkpoint inhibitors that prove effective in cutaneous melanoma do not modify clinical outcome. To date, few studies have focused on deciphering the immunomodulatory features of metastatic UM microenvironment, and there are no prognostic models for clinical use. This highlights the urgent need to understand the delicate interplay between tumor and immune cells acting at the site of metastasis

Characterizing non-tuberculous mycobacteria infection in bronchiectasis

Chronic airway infection is a key aspect of the pathogenesis of bronchiectasis. A growing interest has been raised on non-tuberculous mycobacteria (NTM) infection. We aimed at describing the clinical characteristics, diagnostic process, therapeutic options and outcomes of bronchiectasis patients with pulmonary NTM (pNTM) disease. This was a prospective, observational study enrolling 261 adult bronchiectasis patients during the stable state at the San Gerardo Hospital, Monza, Italy, from 2012 to 2015. Three groups were identified: pNTM disease; chronic P. aeruginosa infection; chronic infection due to bacteria other than P. aeruginosa. NTM were isolated in 32 (12%) patients, and among them, a diagnosis of pNTM disease was reached in 23 cases. When compared to chronic P. aeruginosa infection, patients with pNTM were more likely to have cylindrical bronchiectasis and a “tree-in-bud” pattern, a history of weight loss, a lower disease severity and a lower number of pulmonary exacerbations. Among pNTM patients who started treatment, 68% showed a radiological improvement, and 37% achieved culture conversion without recurrence, while 21% showed NTM isolation recurrence. NTM isolation seems to be a frequent event in bronchiectasis patients, and few parameters might help to suspect NTM infection. Treatment indications and monitoring still remain an important area for future research

Comparison of different sets of immunological tests to identify treatable immunodeficiencies in adult bronchiectasis patients

BACKGROUND: The reported prevalence of immunodeficiencies in bronchiectasis patients is variable depending on the frequency and extent of immunological tests performed. European Respiratory Society guidelines recommend a minimum bundle of tests. Broadening the spectrum of immunological tests could increase the number of patients diagnosed with an immunodeficiency and those who could receive specific therapy. The primary objective of the present study was to assess the performance of different sets of immunological tests in diagnosing any, primary, secondary or treatable immunodeficiencies in adults with bronchiectasis. METHODS: An observational, cross-sectional study was conducted at the Bronchiectasis Program of the Policlinico University Hospital in Milan, Italy, from September 2016 to June 2019. Adult outpatients with a clinical and radiological diagnosis of bronchiectasis underwent the same immunological screening during the first visit when clinically stable consisting of: complete blood count; immunoglobulin (Ig) subclass tests for IgA, IgG, IgM and IgG; total IgE; lymphocyte subsets; and HIV antibodies. The primary endpoint was the prevalence of patients with any immunodeficiencies using five different sets of immunological tests. RESULTS: A total of 401 bronchiectasis patients underwent the immunological screening. A significantly different prevalence of bronchiectasis patients diagnosed with any, primary or secondary immunodeficiencies was found across different bundles. 44.6% of bronchiectasis patients had a diagnosis of immunodeficiency when IgG subclasses and lymphocyte subsets were added to the minimum bundle suggested by the guidelines. CONCLUSION: A four-fold increase in the diagnosis of immunodeficiencies can be found in adults with bronchiectasis when IgG subclasses and lymphocyte subsets are added to the bundle of tests recommended by guidelines

Characterization of the “frequent exacerbator phenotype” in bronchiectasis

Rationale: Exacerbations are key events in the natural history of bronchiectasis, but clinical predictors and outcomes of patients with frequently exacerbating disease are not well described. Objectives: To establish if there is a \u201cfrequent exacerbator phenotype\u201d in bronchiectasis and the impact of exacerbations on long-term clinical outcomes. Methods: We studied patients with bronchiectasis enrolled from 10 clinical centers in Europe and Israel, with up to 5 years of follow-up. Patients were categorized by baseline exacerbation frequency (zero, one, two, or three or more per year). The repeatability of exacerbation status was assessed, as well as the independent impact of exacerbation history on hospitalizations, quality of life, and mortality. Measurements and Main Results: A total of 2,572 patients were included. Frequent exacerbations were the strongest predictor of future exacerbation frequency, suggesting a consistent phenotype.The incident rate ratios for future exacerbations were 1.73 (95% confidence interval [CI], 1.47-2.02; P, 0.0001) for one exacerbation per year, 3.14 (95% CI, 2.70-3.66; P, 0.0001) for two exacerbations, and 5.97 (95% CI, 5.27-6.78; P, 0.0001) for patients with three or more exacerbations per year at baseline. Additional independent predictors of future exacerbation frequency were Haemophilus influenzae and Pseudomonas aeruginosa infection, FEV1, radiological severity of disease, and coexisting chronic obstructive pulmonary disease. Patients with frequently exacerbating disease had worse quality of life and were more likely to be hospitalized during followup. Mortality over up to 5 years of follow-up increased with increasing exacerbation frequency. Conclusions: The frequent exacerbator phenotype in bronchiectasis is consistent over time and shows high disease severity, poor quality of life, and increased mortality during follow-up

Prevalence, risk factors and outcomes of patients coming from the community with sepsis due to multidrug resistant bacteria

Background: Although previous studies showed an increasing prevalence of infections due to multi-drug resistant (MDR) bacteria in the community, specific data on sepsis are lacking. We aimed to assess prevalence, risk factors and outcomes of patients with sepsis due to MDR bacteria. Methods: An observational, retrospective study was conducted on consecutive adult patients coming from the community and admitted to the Policlinico Hospital, Milan, Italy, with a diagnosis of sepsis between January 2011 and December 2015. Primary study outcome was in-hospital mortality. Results: Among 518 patients, at least one MDR bacteria was isolated in 88 (17%). ESBL+ Enterobacteriaceae were the most prevalent MDR bacteria (9.7%) followed by MRSA (3.9%). Independent risk factors for sepsis due to MDR bacteria were septic shock (OR: 2.2; p = 0.002) and hospitalization in the previous 90 days (OR: 2.3; p = 0.003). Independent risk factors for sepsis due to ESBL+ bacteria were hospitalization in the previous 90 days (OR: 2.1; p = 0.02) and stroke (OR: 2.1; p = 0.04). A significantly higher mortality was detected among patients with vs. without MDR bacteria (40.2% vs. 23.1% respectively, p = 0.001). Independent risk factors for mortality among patients with sepsis were coagulation dysfunction (OR: 3.2; p = 0.03), septic shock (OR: 3.2; p = 0.003), and isolation of a MDR bacteria (OR: 4.6; p < 0.001). Conclusion: In light of the prevalence and impact of MDR bacteria causing sepsis in patients coming from the community, physicians should consider ESBL coverage when starting an empiric antibiotic therapy in patients with specific risk factors, especially in the presence of septic shock