Development of clinical tools to estimate the breathing effort during high-flow oxygen therapy: A multicenter cohort study.

INTRODUCTION AND OBJECTIVES: Quantifying breathing effort in non-intubated patients is important but difficult. We aimed to develop two models to estimate it in patients treated with high-flow oxygen therapy. PATIENTS AND METHODS: We analyzed the data of 260 patients from previous studies who received high-flow oxygen therapy. Their breathing effort was measured as the maximal deflection of esophageal pressure (ΔPes). We developed a multivariable linear regression model to estimate ΔPes (in cmH2O) and a multivariable logistic regression model to predict the risk of ΔPes being >10 cmH2O. Candidate predictors included age, sex, diagnosis of the coronavirus disease 2019 (COVID-19), respiratory rate, heart rate, mean arterial pressure, the results of arterial blood gas analysis, including base excess concentration (BEa) and the ratio of arterial tension to the inspiratory fraction of oxygen (PaO2:FiO2), and the product term between COVID-19 and PaO2:FiO2. RESULTS: We found that ΔPes can be estimated from the presence or absence of COVID-19, BEa, respiratory rate, PaO2:FiO2, and the product term between COVID-19 and PaO2:FiO2. The adjusted R2 was 0.39. The risk of ΔPes being >10 cmH2O can be predicted from BEa, respiratory rate, and PaO2:FiO2. The area under the receiver operating characteristic curve was 0.79 (0.73-0.85). We called these two models BREF, where BREF stands for BReathing EFfort and the three common predictors: BEa (B), respiratory rate (RE), and PaO2:FiO2 (F). CONCLUSIONS: We developed two models to estimate the breathing effort of patients on high-flow oxygen therapy. Our initial findings are promising and suggest that these models merit further evaluation.

Imaging of Magnetic Nanoparticles With Permeability Tomography.

Magnetic nanoparticles are being increasingly used in numerous biomedical applications for diagnosis and therapy. During the course of these applications nanoparticle biodegradation and body clearance may occur. In this context, a portable, non-invasive, non-destructive and contactless imaging device can be relevant to trace the nanoparticle distribution before and after the medical procedure. We present a method for in vivo imaging the nanoparticles based on the magnetic induction technique, and we show how to properly tune it for magnetic permeability tomography, maximizing the permeability selectivity. A tomograph prototype was designed and built to demonstrate the feasibility of the proposed method. It includes data collection, signal processing and image reconstruction. Useful selectivity and resolution are achieved on phantoms and animals, proving that the device can be used to monitor the presence of magnetic nanoparticles without requiring any particular sample preparation. By this way, we show that magnetic permeability tomography may become a powerful technique to assist medical procedures.

Survival prediction models in motor neuron disease.

BACKGROUND AND PURPOSE: This study aimed to assess the predictive value of multimodal brain magnetic resonance imaging (MRI) on survival in a large cohort of patients with motor neuron disease (MND), in combination with clinical and cognitive features. METHODS: Two hundred MND patients were followed up prospectively for a median of 4.13 years. At baseline, subjects underwent neurological examination, cognitive assessment and brain MRI. Grey matter volumes of cortical and subcortical structures and diffusion tensor MRI metrics of white matter tracts were obtained. A multivariable Royston-Parmar survival model was created using clinical and cognitive variables. The increase of survival prediction accuracy provided by MRI variables was assessed. RESULTS: The multivariable clinical model included predominant upper or lower motor neuron presentations and diagnostic delay as significant prognostic predictors, reaching an area under the receiver operating characteristic curve (AUC) of a 4-year survival prediction of 0.79. The combined clinical and MRI model including selected grey matter fronto-temporal volumes and diffusion tensor MRI metrics of the corticospinal and extra-motor tracts reached an AUC of 0.89. Considering amyotrophic lateral sclerosis patients only, the clinical model including diagnostic delay and semantic fluency scores provided an AUC of 0.62, whereas the combined clinical and MRI model reached an AUC of 0.77. CONCLUSION: Our study demonstrated that brain MRI measures of motor and extra-motor structural damage, when combined with clinical and cognitive features, are useful predictors of survival in patients with MND, particularly when a diagnosis of amyotrophic lateral sclerosis is made.

Nanoclusters of crystallographically aligned nanoparticles for magnetic thermotherapy: aqueous ferrofluid, agarose phantoms and ex vivo melanoma tumour assessment.

Magnetic hyperthermia is an oncological therapy where magnetic nanostructures, under a radiofrequency field, act as heat transducers increasing tumour temperature and killing cancerous cells. Nanostructure heating efficiency depends both on the field conditions and on the nanostructure properties and mobility inside the tumour. Such nanostructures are often incorrectly bench-marketed in the colloidal state and using field settings far off from the recommended therapeutic values. Here, we prepared nanoclusters composed of iron oxide magnetite nanoparticles crystallographically aligned and their specific absorption rate (SAR) values were calorimetrically determined in physiological fluids, agarose-gel-phantoms and ex vivo tumours extracted from mice challenged with B16-F0 melanoma cells. A portable, multipurpose applicator using medical field settings; 100 kHz and 9.3 kA m-1, was developed and the results were fully analysed in terms of nanoclusters' structural and magnetic properties. A careful evaluation of the nanoclusters' heating capacity in the three milieus clearly indicates that the SAR values of fluid suspensions or agarose-gel-phantoms are not adequate to predict the real tissue temperature increase or the dosage needed to heat a tumour. Our results show that besides nanostructure mobility, perfusion and local thermoregulation, the nanostructure distribution inside the tumour plays a key role in effective heating. A suppression of the magnetic material effective heating efficiency appears in tumour tissue. In fact, dosage had to be increased considerably, from the SAR values predicted from fluid or agarose, to achieve the desired temperature increase. These results represent an important contribution towards the design of more efficient nanostructures and towards the clinical translation of hyperthermia.

Progressive visual function impairment as the predominant symptom of the transition phase to secondary progressive multiple sclerosis: A case report.

BACKGROUND: No reliable indicators of the transition to the progressive course in multiple sclerosis (MS) have been identified so far. The main clinical feature of the progressive phase of MS is usually impairment of walking. Magnetic resonance imaging and optical coherence tomography have emerged recently as promising tools to assess increasing neurodegeneration and axonal loss in disease progression in MS. RESULTS: We report a case of progressive visual impairment as the dominant symptom in the transition to secondary progressive MS. CONCLUSIONS: Impairment of vision, together with walking and cognition, should be considered to better define the transition from relapsing/remitting to secondary-progressive MS.

Selective anti-leukaemic activity of low-dose histone deacetylase inhibitor ITF2357 on AML1/ETO-positive cells.

We analysed the in vitro effects of a new hydroxamate derivative, ITF2357, on AML cells. ITF2357 potently induced histone acetylation. ITF2357 0.1 microM blocked proliferation and induced apoptosis in AML1/ETO-positive Kasumi-1 cells, while AML1/ETO-negative HL60, THP1 and NB4 cell lines were sensitive only to 1 microM ITF2357. Apoptosis was induced by 0.1 microM ITF2357 in AML1/ETO-positive primary blasts and U937-A/E cells induced to express AML1/ETO, but not in U937-A/E cells non-expressing AML1/ETO. In Kasumi-1 cells 0.1 microM ITF2357 induced AML1/ETO degradation through a caspase-dependent mechanism. ITF2357 0.1 microM also determined DNMT1 efflux from, and p300 influx to, the nucleus. Moreover, 0.1 microM ITF2357 determined local H4 acetylation and release of DNMT1, HDAC1 and AML1/ETO, paralleled by recruitment of p300 to the IL-3 gene promoter. ITF2357 treatment, however, did not induce re-expression of IL-3 gene. Accordingly, the methylation level of IL-3 promoter, as well as of several other genes, was unmodified. In conclusion, ITF2357 emerged as an anti-leukaemic agent very potent on AML cells, and on AML1/ETO-positive cells in particular. More relevantly, clearly emerged from our results that ITF2357 could be an ideal agent to treat AML subtypes presenting AML1/ETO fusion protein which determine HDAC involvement in leukaemogenesis.

Class A plexin expression in axotomized rubrospinal and facial motoneurons.

The semaphorin family of guidance molecules plays a role in many aspects of neural development, and more recently semaphorins have been implicated to contribute to the failure of injured CNS neurons to regenerate. While semaphorin expression patterns after neural injury are partially understood, little is known about the expression of their signal transducing transmembrane receptors, the plexins. Therefore, in this study, we compared the expression patterns of all class A plexins (Plxn-A1, A2, A3, A4) in mouse CNS (rubrospinal) and peripheral nervous system (PNS)-projecting (facial) motoneurons for up to two weeks following axonal injury. Using in situ hybridization, immunohistochemistry, and Western blot analysis, in rubrospinal neurons, Plxn-A1 mRNA and protein and Plxn-A4 expression did not change as a result of injury while Plxn-A2 mRNA increased and Plxn-A3 mRNA was undetectable. In facial motoneurons, Plxn-A1, -A3 and -A4 mRNA expression increased, Plxn-A2 mRNA decreased while Plxn-A1 protein expression did not change following injury. We demonstrate that with the exception of the absence of Plxn-A3 mRNA in rubrospinal neurons, both injured rubrospinal (CNS) and facial (PNS) neurons maintain expression of all plexin A family members tested. Hence, there are distinct expression patterns of the individual plexin-A family members suggesting that regenerating rubrospinal and facial motoneurons have a differential ability to transduce semaphorin signals.

Considerations about the complete resection in NSCLC surgery. Review.

The complete resection for NSCLC is analyzed through the study of a series of retrospective surgical reports upon the incomplete resection, due to a microscopic residual tumor at the resection margin. Following Shields' statement in 1974, the incomplete resection represents, in fact, the basic study protocol for the local recurrence following the resection of primary NSCLC. First of all, the obligation for a careful intraoperative pathologic assessment upon the resection margins, clearly emerges from this study. Secondly, two main aspects featuring the incomplete resection have also been pointed out. The first is represented by the historical microscopic residual tumor at the bronchial resection margin, while the second, more recently recognized, is represented by the critical resection margin within the involved ipsilateral mediastinal lymphatic area. The analysis of such different figures leads to different considerations when dealing with the basic matter of the local-regional completeness of resection and the oncological result in terms of cure. In fact, while the problem of the bronchial remnant appears amenable to further improvement by activating the surgical attention, the second, instead, is to be considered unmodifiable by the surgery alone. It basically depends on the extended microvascularity of the large lymphatic mediastinal network which appears to be the crucial factor of risk for such a "lymphatic" resection margin. In conclusion, the matter of complete resection is still open to further research provided that the design is strictly prospective. As a matter of fact, so far the expectation for cure in any apparently completely resected NSCLC is ruled by other well-known factors of prognosis which do not consider the quality of the resected margin at all.

Propagation velocity measurement: autocorrelation technique applied to the electromyogram.

Muscle fibre conduction velocity is an important measurement in electrophysiology, both in the research laboratory and in clinical practice. It is usually measured by placing electrodes spaced at known distances and estimating the transit time of the action potential. The problem, common to all methods, is the estimation of this time delay. Several measurement procedures, in the time and frequency domains, have been proposed. Time-domain strategies usually require two acquisition channels, whereas some frequency-domain methods can be implemented using a single one. The method described operates in the time domain, making use of the autocorrelation function of the difference signal obtained from two needle electrodes and only one acquisition channel. Experimental results were obtained from the electromyogram of two biceps muscles (two adult male subjects, nine records each) under voluntary contraction, yielding an average of 3.58 m s(-1) (SD=0.04 m s(-1)) and 3.37m s(-1) (SD=0.03 m s(-1)), respectively. Several tests showed that the proposed method works properly with electromyogram records as short as 0.3 s.

Listening to our clients: a dangerous proposal.

Although therapeutic thinking and practice have entered their second century, most practitioners remain largely uncertain as to what data to trust, including "what works" and, "why it works." If anything, practitioners' reliance on ever-increasing numbers of theoretical models and either vague or contradictory research findings as primary guidelines to their practice has added to the confusion. What can the practitioner trust? This paper puts forward the "dangerous proposal" that it is of primary value for clinical professionals to place their trust on an often overlooked variable: the clients' statements about their therapy and their relationship to and with their therapist. It is argued that through the clarification of this variable will emerge a better understanding of the nonspecific variables of the therapeutic relationship itself and, as significantly, of the encompassing interrelational realms of discourse evident in all therapeutic models.

A single supply biopotential amplifier.

A biopotential amplifier for single supply operation is presented. It uses a Driven Right Leg Circuit (DRL) to drive the patient's body to a DC common mode voltage, centering biopotential signals with respect to the amplifier's input voltage range. This scheme ensures proper range operation when a single power supply is used. The circuit described is especially suited for low consumption, battery-powered applications, requiring a single battery and avoiding switching voltage inverters to achieve dual supplies. The generic circuit is described and, as an example, a biopotential amplifier with a gain of 60 dB and a DC input range of +/-200 mV was implemented using low power operational amplifiers. A Common Mode Rejection Ratio (CMRR) of 126 dB at 50 Hz was achieved without trimming.

AC coupled three op-amp biopotential amplifier with active DC suppression.

A three op-amps instrumentation amplifier (I.A) with active dc suppression is presented. dc suppression is achieved by means of a controlled floating source at the input stage, to compensate electrode and op-amps offset voltages. This isolated floating source is built around an optical-isolated device using a general-purpose optocoupler, working as a photovoltaic generator. The proposed circuit has many interesting characteristics regarding simplicity and cost, while preserving common mode rejection ratio (CMRR) and high input impedance characteristics of the classic three op-amps I.A. As an example, a biopotential amplifier with a gain of 80 dB, a lower cutoff frequency of 0.1 Hz, and a dc input range of +/- 8 mV was built and tested. Using general-purpose op-amps, a CMRR of 105 was achieved without trimmings.

A transconductance driven-right-leg circuit.

Biopotential measurements are very sensitive to electromagnetic interference (EMI). EMI gets into the acquisition system by many ways, both as differential and common mode signals, driven-right-leg circuits (DRL) are widely used to reduce common mode interference. This paper reports an improvement on the classic DRL. The proposed circuit uses a transconductance amplifier to drive the patient's body. This configuration has some interesting properties, which provide an extended bandwidth for high-frequency EMI rejection (such as fluorescent lights interference). The improvement is around 20 dB for frequencies of few kilohertz and the circuit is easy to compensate for stability. A comparative analysis against a typical DRL is presented, the results obtained have been experimentally tested.

[Decubitus lesions in patients referred to acute and post-acute home nursing care for the elderly in Genova]. / Le lesioni da decubito nella popolazione afferente al nucleo operativo assistenza anziani e RSA post-acuti della USL 3 "Genovese".

The Elderly Services of USL 3 "Genovese" together with the team for Continuing Education designed and implemented a survey on the elderly clients referred to the home care and nursing home services. The aim of the study was to describe the frequency, distribution and severity of pressure ulcers. The data were collected during a period of seven months: from 1st November 1997 to 31st May 1998. One thousand seven hundred and twenty nine clients were observed; 705 (41%) had single or multiple pressure ulcers. Patients with multiple pressure ulcers accounted for 42% of the total. The sacrum was the most affected site (43% of the patients with a single ulcer and 33% with multiple ulcers). Patients with severe pressure ulcers (stages 3 degrees and 4 degrees NPUAP classification) accounted for 42% of the total. Pressure sores were observed in 15% of "at no risk" patients and in 40% of those at low risk (Norton Scale score). The study highlighted a lack of documentation (90% patients) on treatments performed in the hospital and prescribed at discharge for the pressure sores. These findings reflects possibly the fact that this aspect of care is unduly disregarded by nursing personnel, and that a goal-oriented retraining, underlining also the need of appropriate documentation, is warranted.

The new international staging system for lung cancer. Evolution of the system and concerned remarks.

The rationale of the Staging System of Lung Cancer is discussed from his presentation (Mountain, 1985) to the recent revision and proposals of new classifications. Survival rates offered a strong statistical support to the latest revision in 1997. Stage Group have become 7 out of Stage 0 (Tis). In the New Lymph Node Map, station 4 is confirmed as mediastinal (N2). The improved definition of Stage Grouping requires a golden standard of staging and a worldwide consensus on the surgical approach to mediastinal lymphadenectomy. IASLC, the International Association for the Study of Lung Cancer, is now moving to collect a new largest database with the aim to offer the next expected Revision.

The "Will Rogers effect" on stage grading.

Will Rogers phenomenon affects survival statistics applied to clinical research and could determine a misreading of results. Stage migration due to new methods of diagnostic imaging and staging invasive procedures could improve actuarial survival in each stage. TNM System is impaired when survival rates come from different inhomogeneous countries, regions and eras. Randomized trials suffer this fallacious phenomenon when staging depends on the different treatments which are to be evaluated.

The invasive staging and the role of complete resection in the surgical treatment of NSCLC.

Years of debates couldn't solve the discussion between the NSCLC assessment founded on CT scan and mediastinoscopy as in the Western countries and the refined extensive bronchoscopy, CT imaging and exploratory thoracotomy as practiced in Japan. Recently, the clinical onset of combined therapy protocols, the recognised value of the intrathoracic staging (also in the West) and survival rates in the earlier N2 disease moved towards change this steady situation. The role of complete resection in N2 NSCLC is therefore debated from the preoperative assessment to survival results in resected cases. Accuracy of CT scan and cervical mediastinoscopy is discussed also in the light of neoadjuvant therapy. The clinical value of intrathoracic staging is improved by Japanese experiences while a rationale assessment of Complete/Incomplete Resections is defined. Moreover, technical details of intraoperative recognition are cleared.