BACKGROUND: SARS-CoV-2 seems to affect the regulation of pulmonary perfusion. Hypoperfusion in areas of well-aerated lung parenchyma results in a ventilation-perfusion mismatch that can be characterized using subtraction computed tomography angiography (sCTA). This study aims to evaluate the efficacy of oral sildenafil in treating COVID-19 inpatients showing perfusion abnormalities in sCTA. METHODS: Triple-blinded, randomized, placebo-controlled trial was conducted in Chile in a tertiary-care hospital able to provide on-site sCTA scans and ventilatory support when needed between August 2020 and March 2021. In total, 82 eligible adults were admitted to the ED with RT-PCR-confirmed or highly probable SARS-COV-2 infection and sCTA performed within 24 h of admission showing perfusion abnormalities in areas of well-aerated lung parenchyma; 42 were excluded and 40 participants were enrolled and randomized (1:1 ratio) once hospitalized. The active intervention group received sildenafil (25 mg orally three times a day for seven days), and the control group received identical placebo capsules in the same way. Primary outcomes were differences in oxygenation parameters measured daily during follow-up (PaO2/FiO2 ratio and A-a gradient). Secondary outcomes included admission to the ICU, requirement of non-invasive ventilation, invasive mechanical ventilation (IMV), and mortality rates. Analysis was performed on an intention-to-treat basis. RESULTS: Totally, 40 participants were enrolled (20 in the placebo group and 20 in the sildenafil group); 33 [82.5%] were male; and median age was 57 [IQR 41-68] years. No significant differences in mean PaO2/FiO2 ratios and A-a gradients were found between groups (repeated-measures ANOVA p = 0.67 and p = 0.69). IMV was required in 4 patients who received placebo and none in the sildenafil arm (logrank p = 0.04). Patients in the sildenafil arm showed a significantly shorter median length of hospital stay than the placebo group (9 IQR 7-12 days vs. 12 IQR 9-21 days, p = 0.04). CONCLUSIONS: No statistically significant differences were found in the oxygenation parameters. Sildenafil treatment could have a potential therapeutic role regarding the need for IMV in COVID-19 patients with specific perfusion patterns in sCTA. A large-scale study is needed to confirm these results. TRIAL REGISTRATION: Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial, NCT04489446, Registered 28 July 2020, https://clinicaltrials.gov/ct2/show/NCT04489446 .
COVID-19 Drug Treatment , COVID-19 , Sildenafil Citrate , Vasodilator Agents , Administration, Oral , Adult , Aged , COVID-19/physiopathology , Female , Humans , Male , Middle Aged , Pilot Projects , Sildenafil Citrate/administration & dosage , Treatment Outcome , Vasodilator Agents/administration & dosage , Ventilation-Perfusion Ratio
Eosinophilic fasciitis (EF) is a scleroderma-like disease of unknown etiology characterized by cutaneous swelling and induration that affects predominantly the extremities, elevated immune globulins, and peripheral eosinophilia. We report three patients with clinical, laboratory and pathologic characteristics of EF. The main symptoms were cutaneous and included "peau d' orange", groove signs and induration of the affected extremities. Two patients had skin changes after exercising and one had a hypothyroidism. None had extra-cutaneous manifestations. All patients had peripheral eosinophilia. Pathologic findings were thickening and inflammation of the fascia and normal epidermis. Only one patient was treated with prednisone 30 mg daily and showed only moderate improvement. There is no follow up information about the other two cases. EF is a rare disorder classified at times as scleroderma variants. However, its clinical picture, capillary microscopy findings, pathology and prognosis differentiate it from systemic sclerosis
Humans , Male , Female , Adult , Middle Aged , Eosinophilia , Fasciitis
Background: The Infectious Systemic Inflammatory Response syndrome and multiple organic dysfunction have common physiopathological mechanisms. Multiple organic dysfunction can be assessed using severity scores. Aim: To relate cytokine kinetics with a multiple organic dysfunction score during sepsis. Material and methods : Tumor necrosis factor a (TNFa) and interleukin 6 (IL6) kinetics were studied in 25 patients with severe sepsis with less than 48 h of evolution and interleukin 1ß (ILß) kinetics was studied in 13 patients. Measurements were made at 0, 12, 24 and 48 hours after admission to the study, using an ELISA technique. These parameters were correlated with the Marshall multiple organic dysfunction score and survival. Results: Mean age of study subjects was 70 years, the APACHE II score was 16.9ñ6 and the Marshall score was 6.8ñ3.6. Sepsis was of pulmonary origin in 56 percent of patients and intra abdominal in 32 percent. Mortality was 36 percent. TNFa increased during the study period (24.1 pg/ml initially and 37.8 pg/ml at 24 hours, with a slight posterior reduction, p<0.02). These levels had no association with mortality or organic dysfunction. IL6 remained elevated during the first hours and had a tendency to decrease thereafter. Deceased patients had higher values than survivors (306 pg/ml and 55.4 pg/ml respectively, p=0.011). Its values were tightly correlated with Marshall score, with the number of failing organs, with the presence of shock and with probability of dying during hospitalization. IL1ß remained low and was not associated with clinical parameters. Conclusions: There is a tight correlation between the elevation of IL6 and the severity of the Systemic Inflammatory Response and mortality in these patients with sepsis
Humans , Male , Female , Adult , Middle Aged , Cytokines , Systemic Inflammatory Response Syndrome/physiopathology , Interleukin-6 , Interleukin-1 , Multiple Organ Failure/physiopathology , Shock, Septic/physiopathology , Systemic Inflammatory Response Syndrome/mortality
