Early recognition of airway obstruction in Fabry disease and correlation with dyspnea: A case series

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disease that mainly affects kidney, heart and the nervous system, but a respiratory involvement, in the form of obstructive airway disease, has also been described. METHODS: We performed a complete evaluation of pulmonary functional tests (PFTs) on 18 consecutive adult patients with FD. In our cohort we identified 5 subjects with main airway obstruction, but only 2 had airway obstruction in absence of causes other than FD. RESULTS: We found in the majority of patients early signs of airway obstruction, including small-airway obstruction, mild to moderate lung hyperinflation and mild to moderate increase in specific airway resistance. Lung hyperinflation (expressed as increased residual volume at plethysmography) was positively correlated with the presence of dyspnea (both at rest and after exertion). CONCLUSIONS: Therefore complete PFTs, which can detect early signs of airway obstruction, may be considered as a useful screening tool for patients with FD, particularly for those presenting with dyspnea

Respiratory involvement in Fabry disease

Fabry disease is an inherited lysosomal storage disease affecting kidney, heart and nervous system. Respiratory involvement has been described, but complete evaluation of pulmonary functional tests (PFTs) has not been yet performed. Our aim is to evaluate the presence and severity of PFTs alteration in adult patients with Fabry disease. A prospective observational study was performed in adults with Fabry disease referring to the Nephrology clinic of San Gerardo Hospital, Monza, Italy, from 2010 to 2012. Medical history and complete PFTs were recorded for each patient. Percentage of predicted for PFT values was considered. Results are expressed as median [IQR]. 16 patients were enrolled (5 male; median age 48 yrs). Among those, 3 were previous and 1 active smoker (median pack/years 4), 3 had asthma, 6 received enzyme replacement therapy (ERT). 5 patients (31%) presented Forced Expiratory Volume in 1 second (FEV1) mildly decreased (2.1L [1.3-2.8], 81% [44-92]) and a FEV1/FVC ratio<70%, 3 of them (19% of total) had no risk factors for airway obstruction. In 10 subjects (63%), specific Airway Resistance (sRAW) and Residual Volume (RV) were increased (152% [133-171] and 140% [131-152], respectively), while Total Lung Capacity (TLC) was normal in all patients (107% [94-114]). Middle Expiratory Flow (MEF) at 75%, MEF50% and MEF25% were slightly decreased (86.5% [79-103], 78.5% [62-100] and 76.5% [57-96], respectively). A minority of patients had airway obstruction, defined as FEV1/FVC<70%, in absence of causes other than Fabry disease. Slight alterations, as increased sRAW, lung hyperinflation and small-airway obstruction, are present in the majority. Complete PFTs could be useful to detect early signs of airway obstruction in these patients

Possible pathogenetic relationship between Fabry disease and renal cell carcinoma

The occurrence of renal cell carcinoma (RCC) in Fabry disease (FD) is a rare event. We report a deep ultrastructural study of RCC in a patient with a previous histological diagnosis of FD. In order to highlight analogies and differences between the two histological samples, we used the nephrectomy specimen as a 'repeat biopsy', making a dynamic analysis of the evolution of the disease-related kidney damage. Secondly, a comparative ultrastructural analysis between non-neoplastic tissue and cancer demonstrated for the first time the presence of zebra bodies in the tumor cells. Finally, a hypothetical speculation about the relationship between the lysosomal accumulation, the oxidative damage and the genesis of the tumor was performed. The link connected the accumulation of glycosphingolipid globotriaosylceramide, characteristic of FD, with the expression of CD74 and macrophage migration inhibitory factor that may play an important role in tumorigenesis regulated by the Von Hippel-Lindau/hypoxia-inducible factor 1\u3b1 pathway

Hyperspectral imaging acquisition set-up for medical applications

Hyperspectral Imaging (HSI) is a promising practice in research medicine due to its non-contact, non-invasive, non-ionizing, and label-free characteristics. Chromophores, such as haemoglobin and melanin, are responsible for the chemical structure of tissues and determine their spectral properties. Therefore, hyperspectral technologies might serve the role of tissue diagnosis, aiding physicians during surgical or clinical operations. Hence, hyperspectral cameras produce the data used by machine and deep learning algorithms to discriminate healthy from damaged tissues. Nevertheless, data quality remains an issue, especially concerning the small-sized medical dataset available to research. Here, we propose a hyperspectral imaging blueprint, designed to work with push broom sensors, representing one of the highest quality transducers to acquire spectral data. Indeed, push broom sensors only seize one scene line at a time, offering high spatial and spectral resolutions. It can work in any scenario, such as dermatological or surgical, involving a motionless subject. We designed the system to be affordable, open-source and robust. Therefore, it comprises Python libraries, an Arduino one board, a Nema17 stepper motor, its driver controller, and a recirculating ball screw for accurate movement. Furthermore, it offers a diode-based targeting system, attached to a 3D printed circular crown and built to hit the image capture and measure the right focusing distance. We equipped the blueprint with a graphical user interface to let physicians interact with the camera, accurately move it, and acquire the diagnostic data needed

On-Chip Magnetic Platform for Single-Particle Manipulation with Integrated Electrical Feedback

Methods for the manipulation of single magnetic particles have become very interesting, in particular for in vitro biological studies. Most of these studies require an external microscope to provide the operator with feedback for controlling the particle motion, thus preventing the use of magnetic particles in high-throughput experiments. In this paper, a simple and compact system with integrated electrical feedback is presented, implementing in the very same device both the manipulation and detection of the transit of single particles. The proposed platform is based on zig-zag shaped magnetic nanostructures, where transverse magnetic domain walls are pinned at the corners and attract magnetic particles in suspension. By applying suitable external magnetic fields, the domain walls move to the nearest corner, thus causing the step by step displacement of the particles along the nanostructure. The very same structure is also employed for detecting the bead transit. Indeed, the presence of the magnetic particle in suspension over the domain wall affects the depinning field required for its displacement. This characteristic field can be monitored through anisotropic magnetoresistance measurements, thus implementing an integrated electrical feedback of the bead transit. In particular, the individual manipulation and detection of single 1-μm sized beads is demonstrated

ENUBET: A monitored neutrino beam for high precision cross section measurements

International audienceThe main source of systematic uncertainty on neutrino cross section measurements at the GeV scale is represented by the poor knowledge of the initial flux. The goal of cutting down this uncertainty to 1% can be achieved through the monitoring of charged leptons produced in association with neutrinos, by properly instrumenting the decay region of a conventional narrow-band neutrino beam. Large angle muons and positrons from kaons are measured by a sampling calorimeter on the decay tunnel walls (tagger), while muon stations after the hadron dump can be used to monitor the neutrino component from pion decays. This instrumentation can provide a full control on both the muon and electron neutrino fluxes at all energies. Furthermore, the narrow momentum width (<10%) of the beam provides a O(10%) measurement of the neutrino energy on an event by event basis, thanks to its correlation with the radial position of the interaction at the neutrino detector. The ENUBET project has been funded by the ERC in 2016 to prove the feasibility of such a monitored neutrino beam and is cast in the framework of the CERN neutrino platform (NP06) and the Physics Beyond Colliders initiative. In our contribution, we summarize the ENUBET design, physics performance and opportunities for its implementation in a timescale comparable with next long baseline neutrino experiments

Mortality in KPC-producing Klebsiella pneumoniae bloodstream infections: a changing landscape

Objectives: To assess the impact of carbapenem resistance on mortality in Klebsiella pneumoniae bloodstream infection (BSI) in the era of novel β-lactam/β-lactamase inhibitor combinations. Material and methods: Retrospective study of patients with K. pneumoniae BSI between January and August 2020 in 16 centres (CARBANEW study within the MULTI-SITA project). Results: Overall, 426 patients were included: 107/426 (25%) had carbapenem-resistant K. pneumoniae (CR-Kp) BSI and 319/426 (75%) had carbapenem-susceptible K. pneumoniae (CS-Kp) BSI. Crude cumulative 30 day mortality was 33.8% and 20.7% in patients with, respectively, CR-Kp BSI and CS-Kp BSI (P = 0.027). Carbapenemase production or carbapenemase-encoding genes were detected in 84/98 tested CR-Kp isolates (85.7%), mainly KPC (78/84; 92.9%). Ceftazidime/avibactam was the most frequently used appropriate therapy for CR-Kp BSI (80/107; 74.7%). In multivariable analyses, variables showing an unfavourable association with mortality after correction for multiple testing were age-adjusted Charlson comorbidity index (HR 1.20; 95% CI 1.10-1.31, P &lt; 0.001) and Pitt score (HR 1.33; 95% CI 1.15-1.55, P &lt; 0.001), but not carbapenem resistance (HR 1.28, 95% CI 0.74-2.22, P = 0.410). In a propensity score-matched analysis, there was no difference in mortality between patients appropriately treated with ceftazidime/avibactam for CR-Kp BSI and patients appropriately treated with other agents (mainly meropenem monotherapy or piperacillin/tazobactam monotherapy) for CS-Kp BSI (HR 1.07; 95% CI 0.50-2.29, P = 0.866). Conclusions: Our results suggest that the increased mortality in CR-Kp BSI compared with CS-Kp BSI is not (or no longer) dependent on the type of therapy in areas where ceftazidime/avibactam-susceptible KPC-producing isolates are the most prevalent type of CR-Kp

Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016

Objectives: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-na\uefve patients from 2006 to 2016. Methods: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. Results: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/\u3bcL [interquartile range (IQR) 169\u2013521 cells/\u3bcL], and the median viral load was 4.7 log10 HIV-1 RNA copies/mL (IQR 4.1\u20135.3 log10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P&nbsp;=&nbsp;0.003): TDR to NRTIs from 9.9 to 2.9% (P&nbsp;=&nbsp;0.003) and TDR to NNRTIs from 5.1 to 3.7% (P&nbsp;=&nbsp;0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P&nbsp;&lt;&nbsp;0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P&nbsp;&lt;&nbsp;0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P&nbsp;=&nbsp;0.04) but not in non-B subtypes (from 6.1 to 5.8%; P&nbsp;=&nbsp;0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93\u20134.39; P&nbsp;&lt;&nbsp;0.001], lower viral load (per log10 higher: AOR 0.86; 95% CI 0.75\u20130.99; P&nbsp;=&nbsp;0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40\u20130.91; P&nbsp;=&nbsp;0.01), and earlier calendar year (per 1&nbsp;year more recent: AOR 0.95; 95% CI 0.91\u20130.99; P&nbsp;=&nbsp;0.02). Conclusions: The prevalence of HIV-1 TDR has declined during the last 10&nbsp;years in Italy

The relationships of personal resources with symptom severity and psychosocial functioning in persons with schizophrenia: results from the Italian Network for Research on Psychoses study

The relationships of personal resources with symptom severity and psychosocial functioning have never been tested systematically in a large sample of people with schizophrenia. We applied structural equation models to a sample of 921 patients with schizophrenia collected in a nationwide Italian study, with the aim to identify, among a large set of personal resources, those that may have an association with symptom severity or psychosocial functioning. Several relevant demographic and clinical variables were considered concurrently. Poor service engagement and poor recovery style, as well as older age and younger age at onset, were related to greater symptom severity and poorer social functioning. Higher resilience and higher education were related to better social functioning only. Poor problem-focused coping and internalized stigma, as well as male gender and depression, were related to symptom severity only. The explored variables showed distinctive and partially independent associations with symptom severity and psychosocial functioning. A deeper understanding of these relationships may inform treatment decisions