Factors affecting signal quality in implantable cardiac monitors with long sensing vector.

PURPOSE: Electrical artefacts are frequent in implantable cardiac monitors (ICMs). We analyzed the subcutaneous electrogram (sECG) provided by an ICM with a long sensing vector and factors potentially affecting its quality. METHODS: Consecutive ICM recipients underwent a follow-up where demographics, body mass index (BMI), implant location, and surface ECG were collected. The sECG was then analyzed in terms of R-wave amplitude and P-wave visibility. RESULTS: A total of 84 patients (43% female, median age 68 [58-76] years) were enrolled at 3 sites. ICMs were positioned with intermediate inclination (n = 44, 52%), parallel (n = 35, 43%), or perpendicular (n = 5, 6%) to the sternum. The median R-wave amplitude was 1.10 (0.72-1.48) mV with P waves readily visible in 69.2% (95% confidence interval, CI: 57.8%-79.2%), partially visible in 23.1% [95% CI: 14.3%-34.0%], and never visible in 7.7% [95% CI: 2.9%-16.0%] of patients. Men had higher R-wave amplitudes compared to women (1.40 [0.96-1.80] mV vs 1.00 [0.60-1.20] mV, P = .001), while obese people tended to have lower values (0.80 [0.62-1.28] mV vs 1.10 [0.90-1.50] mV, P = .074). The P-wave visibility reached 86.2% [95% CI: 68.3%-96.1%] in patients with high-voltage P waves (≥0.2 mV) at surface ECG. The sECG quality was not affected by implant site. CONCLUSION: In ordinary clinical practice, ICMs with long sensing vector provided median R-wave amplitude above 1 mV and reliable P-wave visibility of nearly 70%, regardless of the position of the device. Women and obese patients showed lower but still very good signal quality.

Use of the FebriDx point-of-care test for the exclusion of SARS-CoV-2 diagnosis in a population with acute respiratory infection during the second (COVID-19) wave in Italy.

OBJECTIVE: Evaluate the real-world accuracy of Myxovirus resistance protein A (MxA) detected by the rapid, point-of-care FebriDx test during the second-wave pandemic in Italy in patients with acute respiratory infection (ARI) and a clinical suspicion of COVID-19. DESIGN AND METHODS: Prospective, observational, diagnostic accuracy study whereby hospitalized patients with ARI were consecutively enrolled in a single tertiary care center in Italy from August 1, 2020 to January 31, 2021. RESULTS: COVID-19 was diagnosed in 136/200 (68.0%) patients and Non-COVID-19 was diagnosed in 64/200 (32.0%) patients. COVID-19 patients were younger and had a lower Charlson comorbidity index compared to Non-COVID-19 patients (p < 0.001). Concordance between FebriDx, MxA and rt-PCR for SARS-CoV-2 (gold standard) was good (k 0.93, 95% CI 0.87-0.99). Overall sensitivity and specificity were 97.8% [95% CI 93.7-99.5] and 95.3% [95% CI 86.9%-99.0%], respectively. FebriDx demonstrated a negative predictive value of 95.3% (95% CI 86.9-99.0) for an observed disease prevalence of 68%. CONCLUSIONS: FebriDx MxA showed high diagnostic accuracy to identify COVID-19 and could be considered as a real-time triage tool to streamline the management of suspected COVID-19 patients. FebriDx also detected bacterial etiology in Non-COVID-19 patients suggesting good performance to distinguish bacterial from viral respiratory infection.

Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study.

Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus high-flow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.

Inter-individual differences in control of alveolar capillary blood volume in exercise and hypoxia.

We compared by non-invasive technique the adaptive response of alveolar capillary network to edemagenic conditions (exercise and high altitude [HA, PIO2 107mmHg] in subjects with different resting sea level (SL) capillary blood volume (normalized to alveolar volume, Vc/Va): Group 1 (N=10, Vc/Va=16.1±6.8ml/L- mean±SD) and Group 2 (N=10, Vc/Va=25±7.7). In Group 1 Vc/Va remained unchanged in HA at rest and increased during exercise at SL (26.3±8.6) and HA (28.75±10.2); in Group 2 Vc/Va significantly decreased in HA (19±6) and did not increase in exercise at SL and HA. We hypothesize that Group2 exerts a tight control on Vc/Va being more exposed to the risk of lung edema due to inborn greater microvascular permeability. Conversely, Group 1 appears more resistant to lung edema given the large capillary recruitment in the most edemagenic condition. The 4-fold increase in frequency dependence of respiratory resistance in Group2 in HA stems for greater proneness for lung water perturbation compared to Group 1.

Enantioselective separation of the novel antidepressant mirtazapine and its main metabolites by CEC.

In this work, the simultaneous enantioseparation of the second-generation antidepressant drug mirtazapine and its main metabolites 8-hydroxymirtazapine and N-desmethylmirtazapine by chiral CEC is reported. The separation of all enantiomers under study was achieved employing a capillary column packed with a vancomycin-modified diol stationary phase. With the aim to optimize the separation of the three pairs of enantiomers in the same run, different experimental parameters were studied including the mobile phase composition (buffer concentration and pH, organic modifier type and ratio, and water content), stationary phase composition, and capillary temperature. A capillary column packed with vancomycin mixed with silica particles in the ratio (3:1) and a mobile phase composed of 100 mM ammonium acetate buffer (pH 6)/H(2)O/MeOH/ACN (5:15:30:50, by vol.) allowed the complete enantioresolution of each pair of enantiomers but not the simultaneous separation of all the studied compounds. For this purpose, a packing bed composed of vancomycin-CSP only was tested and the baseline resolution of the three couples of enantiomers was achieved in a single run in less than 30 min, setting the applied voltage and temperature at 25 kV and 20 degrees C, respectively. In order to show the potential applicability of the developed CEC method to biomedical analysis, a study concerning precision, sensitivity, and linearity was performed. The method was then applied to the separation of the enantiomers in a human urine sample spiked with the studied compounds after suitable SPE procedure with strong cation-exchange (SCX) cartridges.

Arterial stiffening influence of sympathetic nerve activity: evidence from hand transplantation in humans.

Studies in animals and humans suggest that sympathetic activity exerts a stiffening influence on large and middle-sized artery walls. We sought to obtain further evidence on this issue by measuring radial artery distensibility in an allotransplanted and thus denervated hand using the contralateral artery as control. In 2 men, blood pressure was measured by a semiautomatic device (Dinamap). Diastolic diameter, systo-diastolic diameter excursion (ultrasound Wall Track system), and distensibility (Reneman formula) of both radial arteries were measured at a level corresponding to 4 cm below the suture of the transplanted hand 40 days after surgery and every 4 weeks for the next 6 months. After surgery, systo-diastolic diameter excursion and distensibility were much greater in the transplanted radial artery than in the contralateral vessel, reaching values similar to the contralateral ones after 4 months, when signs of reinnervation of the transplanted hands had appeared. Radial deinnervation was accompanied by an increased arterial distensibility, which provides further evidence of the sympathetic stiffening effect on arterial wall in humans.

[Study of arterial distensibility in man. Modulating mechanisms, pathological conditions and effects of treatment]. / Studio della distensibilità arteriosa nell'uomo. Quali i meccanismi di modulazione, come varia in condizioni patologiche ed effetto della terapia.

The reduction of large arterial distensibility has several adverse consequences for the cardiovascular system. This paper reviews the evidence we have obtained by measuring distensibility through quantification of changes in arterial diameter vs blood pressure changes at large elastic and middle size muscle artery sites. Evidence shows that arterial distensibility is reduced in conditions such as hypercholesterolemia, hypertension, diabetes, and congestive heart failure. In some conditions (e.g. hypertension) the alterations are not uniformly distributed in the arteries of different structure and size whereas in others (e.g. diabetes and heart failure) they are widespread. In diabetes evidence is available that distensibility changes occur early in the course of the disease. Evidence is also available that in all above conditions treatment can improve arterial distensibility thereby reversing the initial abnormality. This is due to a variable combination of structural and functional factors. However, technical ability to determine their precise role in distensibility changes in humans is limited.