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 highflow 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.

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.

Abstract-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. Key Words: denervation Ⅲ sympathetic nervous system Ⅲ transplantation S ympathetic nerve activity exerts a "tonic" stiffening influence on arterial wall. 1,2 This has been shown in animals in which chemical sympathectomy was accompanied by an increase in carotid artery distensibility. 3 It has also been shown in humans in whom anesthesia of the brachial plexus and anesthesia of the low spinal cord and lumbar sympathectomy were all followed by an increase in the distensibility of the radial or the femoral artery, reflecting the stiffening effect neural influences exerted on the vessel wall. 4 Our hospital started a program of allotransplantation of the hand 2 years ago. This gave us a chance to determine what happens to arterial distensibility in transplanted organs and to make use of another human "model" on which to study the relationship between sympathetic tone and arterial distensibility, which could be measured at various times after the surgical intervention in the radial artery below the transplantation line, using the values obtained from the contralateral vessel as control. This article reports the results obtained in 2 patients. MethodsWe studied 2 men (patient 1, age 35 years; patient 2, age 31 years) who underwent allotransplantation of the right hand, which had been lost in a previous car accident. Both patients underwent a routine pretransplantation investigation and morphological and functional testing of the forearm stumps to ensure immunologic and mechanical donor-recipient compatibility. They were administered treatment with monoclonal antibodies anti-CD25 (Baxilimab, Simulect), FK506 (tacrolimus, Prograf), mycophenolate mofetil (Cell Cept), and prednisone immediately after surgery to prevent graft rejection. Maintenance therapy was unchanged throughout the study duration. The post -treatment program of rehabilitation (started as the swelling subsided...

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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.