Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness.

OBJECTIVES: To assess the characteristics and risk factors for mortality in patients with severe coronavirus disease-2019 (COVID-19) treated with tocilizumab (TCZ), alone or in combination with corticosteroids (CS). METHODS: From March 17 to April 7, 2020, a real-world observational retrospective analysis of consecutive hospitalized adult patients receiving TCZ to treat severe COVID-19 was conducted at our 750-bed university hospital. The main outcome was all-cause in-hospital mortality. RESULTS: A total of 1,092 patients with COVID-19 were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186 patients, 155 (83.3 %) patients were receiving noninvasive ventilation when TCZ was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (±4.3) and 4.3 days (±3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR = 1.09, p < 0.001), chronic heart failure (HR = 4.4, p = 0.003), and chronic liver disease (HR = 4.69, p = 0.004). The use of CS, in combination with TCZ, was identified as a protective factor against mortality (HR = 0.26, p < 0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. CONCLUSIONS: In patients with severe COVID-19 receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed a beneficial effect in preventing in-hospital mortality.

Development of a novel automatable fabrication method based on electrospinning co electrospraying for rotator cuff augmentation patches.

Rotator cuff tear is one of the most common shoulder diseases. Rotator cuff augmentation (RCA) is trying to solve the high retear failure percentage after the surgery procedures (20-90%). The ideal augmentation patch must provide a temporal mechanical support during the healing process. In this work, we proposed a simple method for the fabrication of synthetic RCA patches. This method combines the use of electrospraying to produce poly-L-lactic-co-ε-caprolactone (PLC) films in an organogel form and electrospinning to produce poly(lactic) acid (PLA) nanofibers. The device consists in a combination of layers, creating a multilayered construct, enabling the possibility of tuning its mechanical properties and thickness. Besides, both techniques are simple to escalate for industrial production. A complete characterization has been performed to optimize the involved number of layers and production time of PLC films and PLA nanofibers fabrication, obtaining a final optimal configuration for RCA devices. Structural, mechanical and suture properties were evaluated. Also, the possibility of surface functionalization to improve the bioactivity of the scaffold was studied, adding aligned electrospun PLA nanofibers on the surface of the device to mimic the natural tendon topography. Surface modification was characterized by culturing adult normal human dermal fibroblasts. Lack of toxicity was detected for material presented, and cell alignment shape orientation guided by aligned fibers, mimicking tendon structure, was obtained. Cell proliferation and protein production were also evaluated.

Postoperative analgesic effects of either a constant rate infusion of fentanyl, lidocaine, ketamine, dexmedetomidine, or the combination lidocaine-ketamine-dexmedetomidine after ovariohysterectomy in dogs.

OBJECTIVE: To evaluate the postoperative analgesic effects of a constant rate infusion (CRI) of either fentanyl (FENT), lidocaine (LIDO), ketamine (KET), dexmedetomidine (DEX), or the combination lidocaine-ketamine-dexmedetomidine (LKD) in dogs. STUDY DESIGN: Randomized, prospective, blinded, clinical study. ANIMALS: Fifty-four dogs. METHODS: Anesthesia was induced with propofol and maintained with isoflurane. Treatments were intravenous (IV) administration of a bolus at start of anesthesia, followed by an IV CRI until the end of anesthesia, then a CRI at a decreased dose for a further 4 hours: CONTROL/BUT (butorphanol 0.4 mg kg(-1), infusion rate of saline 0.9% 2 mLkg(-1) hour(-1)); FENT (5 µg kg(-1), 10 µg kg(-1) hour(-1), then 2.5 µg kg(-1) hour(-1)); KET (1 mgkg(-1) , 40 µg kg(-1) minute(-1), then 10 µg kg(-1) minute(-1) ; LIDO (2 mg kg(-1), 100 µg kg(-1) minute(-1), then 25 µg kg(-1) minute(-1)); DEX (1 µgkg(-1), 3 µg kg(-1) hour(-1), then 1 µg kg(-1) hour(-1)); or a combination of LKD at the aforementioned doses. Postoperative analgesia was evaluated using the Glasgow composite pain scale, University of Melbourne pain scale, and numerical rating scale. Rescue analgesia was morphine and carprofen. Data were analyzed using Friedman or Kruskal-Wallis test with appropriate post-hoc testing (p < 0.05). RESULTS: Animals requiring rescue analgesia included CONTROL/BUT (n = 8), KET (n = 3), DEX (n = 2), and LIDO (n = 2); significantly higher in CONTROL/BUT than other groups. No dogs in LKD and FENT groups received rescue analgesia. CONTROL/BUT pain scores were significantly higher at 1 hour than FENT, DEX and LKD, but not than KET or LIDO. Fentanyl and LKD sedation scores were higher than CONTROL/BUT at 1 hour. CONCLUSIONS AND CLINICAL RELEVANCE: LKD and FENT resulted in adequate postoperative analgesia. LIDO, CONTROL/BUT, KET and DEX may not be effective for treatment of postoperative pain in dogs undergoing ovariohysterectomy.

Lidocaine, dexmedetomidine and their combination reduce isoflurane minimum alveolar concentration in dogs.

The effects of intravenous (i.v.) lidocaine, dexmedetomidine and their combination delivered as a bolus followed by a constant rate infusion (CRI) on the minimum alveolar concentration of isoflurane (MACISO) in dogs were evaluated. Seven healthy adult dogs were included. Anaesthesia was induced with propofol and maintained with isoflurane. For each dog, baseline MAC (MACISO/BASAL) was determined after a 90-minute equilibration period. Thereafter, each dog received one of the following treatments (loading dose, CRI): lidocaine 2 mg kg(-1), 100 µg kg(-1) minute(-1); dexmedetomidine 2 µg kg(-1), 2 µg kg(-1) hour(-1); or their combination. MAC was then determined again after 45- minutes of treatment by CRI. At the doses administered, lidocaine, dexmedetomidine and their combination significantly reduced MACISO by 27.3% (range: 12.5-39.2%), 43.4% (33.3-53.3%) and 60.9% (46.1-78.1%), respectively, when compared to MACISO/BASAL. The combination resulted in a greater MACISO reduction than the two drugs alone. Their use, at the doses studied, provides a clinically important reduction in the concentration of ISO during anaesthesia in dogs.

Evaluation of the isoflurane-sparing effects of fentanyl, lidocaine, ketamine, dexmedetomidine, or the combination lidocaine-ketamine-dexmedetomidine during ovariohysterectomy in dogs.

OBJECTIVE: To evaluate the isoflurane-sparing effects of an intravenous (IV) constant rate infusion (CRI) of fentanyl, lidocaine, ketamine, dexmedetomidine, or lidocaine-ketamine-dexmedetomidine (LKD) in dogs undergoing ovariohysterectomy. STUDY DESIGN: Randomized, prospective, blinded, clinical study. ANIMALS: Fifty four dogs. METHODS: Anesthesia was induced with propofol and maintained with isoflurane with one of the following IV treatments: butorphanol/saline (butorphanol 0.4 mg kg(-1), saline 0.9% CRI, CONTROL/BUT); fentanyl (5 µg kg(-1), 10 µg kg(-1) hour(-1), FENT); ketamine (1 mg kg(-1), 40 µg kg(-1) minute(-1), KET), lidocaine (2 mg kg(-1), 100 µg kg(-1) minute(-1), LIDO); dexmedetomidine (1 µg kg(-1), 3 µg kg(-1) hour(-1), DEX); or a LKD combination. Positive pressure ventilation maintained eucapnia. An anesthetist unaware of treatment and end-tidal isoflurane concentration (Fe'Iso) adjusted vaporizer settings to maintain surgical anesthetic depth. Cardiopulmonary variables and Fe'Iso concentrations were monitored. Data were analyzed using anova (p < 0.05). RESULTS: At most time points, heart rate (HR) was lower in FENT than in other groups, except for DEX and LKD. Mean arterial blood pressure (MAP) was lower in FENT and CONTROL/BUT than in DEX. Overall mean ± SD Fe'Iso and % reduced isoflurane requirements were 1.01 ± 0.31/41.6% (range, 0.75 ± 0.31/56.6% to 1.12 ± 0.80/35.3%, FENT), 1.37 ± 0.19/20.8% (1.23 ± 0.14/28.9% to 1.51 ± 0.22/12.7%, KET), 1.34 ± 0.19/22.5% (1.24 ± 0.19/28.3% to 1.44 ± 0.21/16.8%, LIDO), 1.30 ± 0.28/24.8% (1.16 ± 0.18/32.9% to 1.43 ± 0.32/17.3%, DEX), 0.95 ± 0.19/54.9% (0.7 ± 0.16/59.5% to 1.12 ± 0.16/35.3%, LKD) and 1.73 ± 0.18/0.0% (1.64 ± 0.21 to 1.82 ± 0.14, CONTROL/BUT) during surgery. FENT and LKD significantly reduced Fe'Iso. CONCLUSIONS AND CLINICAL RELEVANCE: At the doses administered, FENT and LKD had greater isoflurane-sparing effect than LIDO, KET or CONTROL/BUT, but not at all times. Low HR during FENT may limit improvement in MAP expected with reduced Fe'Iso.

True vertical validation in facial orthognathic surgery planning.

OBJECTIVES: To validate the effectiveness of the original standards of True Vertical (TV) Subnasal Line in orthognatic surgery planning. The present study evaluates the changes occurring in patients with skeletal Class II alterations programmed for orthognathic surgery with a view to improving their facial profile. STUDY DESIGN: [corrected] We showed a series of black profiles (composed by a first control group of subjects with normal occlusion, and another two additional groups comprised patients before -Group 2- and after orthognatic surgical correction of Class II malocclusion -Group 3-) for three groups of observers (orthodontists, surgeons and laypeople). The facial images became black silhouettes in order to determine a series of parameters (including aesthetic assessment) by means of the observers. Their observation were assessed using a 5-point Likert scale. RESULTS: The sample was composed of 52 profile's subjects who were tested for a total of 72 observers. Aesthetic assessment yielded mean scores of 2.57, 1.67 and 2.46 for groups 1, 2 and 3, respectively. There was a statistically significant difference (p<0.001) between group 1 versus group 2. There were no significant differences in terms of observer assessment of aesthetics, with the exception of a wider perception range among the orthodontists. Regarding the studied profile measures, significant differences were recorded for point B' and Pg' (p<0.02) between groups 2 and 3 (i.e., pre- versus post-surgery). CONCLUSIONS: The results of our study suggest the subnasale vertical and sagittal measures of the lower third of the face are decisive in facial aesthetics, and therefore also for the planning of orthognathic surgery. Consequently, these aesthetic parameters can be used as an objective tool for the planning of orthodontic treatment. Key words:Facial profile, Class II, orthognathic surgery, cephalometric analysis, facial soft tissue, subnasale vertical.