Effect of dexmedetomidine constant rate infusion on the analgesic duration of peripheral nerve blocks in dogs: a randomized clinical study.

The aim of this study was to evaluate whether a constant rate infusion of dexmedetomidine could prolong the analgesic effect of peripheral nerve blocks. Twenty client-owned dogs were enrolled and randomly divided into 2 groups. The DEX group received dexmedetomidine infusion at 1 mcg kg-1 h-1, and the NaCl group received an equivalent volume infusion of saline. Infusions were started after securing vascular access and continued for 10 min, after which intravenous (IV) methadone at 0.2 mg kg-1 and propofol to effect were administered. All animals were maintained with isoflurane in 70% oxygen. Sciatic, saphenous and obturator nerve blocks were performed using 0.1 mL kg-1 0.5% ropivacaine/block. Intraoperative fentanyl was administered if the heart rate and/or mean arterial pressure (MAP) increased > 15% from the previous measurement, and vasopressors were administered if MAP was ≤ 70 mmHg. Postoperative pain was assessed every hour using the Glasgow Composite Pain Scale (GCPS) until the first rescue analgesia administration. Postoperative rescue analgesia (methadone (0.2 mg kg-1 IV) and carprofen (2 mg kg-1 IV)) was administered if the pain score was higher than 6/24 or 5/20. Duration of analgesia was defined as the time between the nerve block procedure and initial postoperative rescue analgesia. Ambulation, proprioception, and skin sensitivity were evaluated to assess the duration of the motor and sensory block. A Student T and chi-square test were used to compare groups for duration of postoperative analgesia and intraoperative fentanyl and vasopressor use, respectively (p values ≤ 0.5 considered significant). A greater number of dogs in the NaCl group required fentanyl (5/10 p = 0.03) and vasopressors (8/10, p = 0.02) than did those in the DEX group (0/10 and 2/10, respectively). The duration of postoperative analgesia was significantly longer (604 ± 130 min) in the DEX group than in the NaCl group (400 ± 81 min, p = 0.0005).Dexmedetomidine infusion at 1 mcg kg-1 h-1 delays the time to first administration of rescue analgesia and reduces intraoperative analgesic and vasopressor requirements during Tibial Tuberosity Advancement surgery.

Circulating extracellular vesicles and small non-coding RNAs cargo in idiopathic inflammatory myopathies reveal differences across myositis subsets.

OBJECTIVE: To investigate the epigenetic footprint of idiopathic inflammatory myopathies (IIM) through characterization of circulating extracellular vesicles (EVs) and the expression of EV-derived small non-coding RNAs (sncRNAs). METHODS: In this cross-sectional study, EVs were isolated by size-exclusion chromatography from plasma of patients with IIM and age- and sex-matched healthy donors (HD). EV-derived sncRNAs were sequenced and quantified using Next-Generation Sequencing (NGS). Following quality control and normalization, filtered count reads were used for differential microRNA (miRNA) and piwi-interacting RNA (piRNA) expression analyses. Putative gene targets enriched for pathways implicated in IIM were analyzed. Patients' clinical and laboratory characteristics at the time of sampling were recorded. RESULTS: Forty-seven IIM patients and 45 HD were enrolled. MiR-486-5p (p < 0.01), miR-122-5p, miR-192-5p, and miR-32-5p were significantly upregulated (p < 0.05 for all), while miR-142-3p (p < 0.001), miR-141-3p (p < 0.01), let-7a-5p (p < 0.05) and miR-3613-5p (p < 0.05) downregulated in EVs from IIM patients versus HD. MiR-486-5p was associated with raised muscle enzymes levels. Several target genes of up/downregulated miRNAs in IIM participate in inflammation, necroptosis, interferon and immune signaling. Six piRNAs were significantly dysregulated in IIM EVs versus HD (p < 0.05). Within IIM, miR-335-5p was selectively upregulated and miR-27a-5p downregulated in dermatomyositis (n = 21, p < 0.01). Finally, plasma EV levels were significantly increased in cancer-associated myositis (CAM, n = 12) versus non-CAM IIM (n = 35, p = 0.02) and HD (p < 0.01). EVs cargo in CAM was significantly enriched of let-7f-5p and depleted of miR-143-3p. CONCLUSION: Through an unbiased screening of EV-derived sncRNAs, we characterize miRNAs and piRNAs in the EVs cargo as potential biomarkers and modifiers of diverse IIM phenotypes.

Evaluation of the Quality of Recovery from General Anesthesia in Dogs with Two Different Low Doses of Dexmedetomidine.

The purpose of this study was to evaluate the quality of recovery from general anesthesia with the administration of two low doses of dexmedetomidine in canine patients. For this blind randomized clinical trial study, 30 dogs undergoing general anesthesia for diagnostic procedures or elective surgery (ovariectomy/castration) were included. The patients were randomly divided into three groups, and at the end of anesthesia, they received a bolus of dexmedetomidine at 1 mcg/kg IV (D1), or a bolus of dexmedetomidine at 0.5 mcg/kg (D0.5), or a bolus of NaCl, in a total of 0.5 mL of solution for all three groups. After administration of the bolus, the anesthetist monitored the patients every 5 min by measuring heart rate, systolic and mean blood pressure, respiratory rate, and oxygen saturation. The quality of recovery was also assessed using 4 different scales. The extubation time, time of headlift, and standing position were also recorded. Both groups receiving dexmedetomidine had better awakening and a lower incidence of delirium when compared to saline administration. The heart rate was lower, while the systolic pressure was higher in the two groups D1 and D0.5 compared to the NaCl with a low presence of atrioventricular blocks. The extubation time resulted significantly higher in the D1 (17 ± 6 min) compared to the D0.5 (10 ± 4 min) and NaCl (8 ± 3 min) (p < 0.0001); the headlift time D1 (25 ± 10 min) resulted significantly longer than the NaCl group (11 ± 5 min) (p = 0.0023) but not than the D0.5 (18 ± 9 min). No significant differences were found among the three groups for standing positioning (D1 50 ± 18 min, D0.5 39 ± 22 min, NaCl 28 ± 17 min). The preventive administration of a bolus of dexmedetomidine at a dosage of 0.5 mcg/kg or 1 mcg/kg IV during the recovery phase improves the quality of recovery in patients undergoing general anesthesia.

Impact of a Dexmedetomidine Intravenous Infusion in Septic Dogs: Preliminary Study.

The purpose of this study was to determine if a continuous rate infusion (CRI) of dexmedetomidine decreases vasopressor requirements in septic dogs undergoing surgery. Vital parameters, sequential organ failure assessment (SOFA) score, vasopressor requirement, and 28-day mortality were recorded. Dogs were randomly divided into two groups: a dexmedetomidine (DEX) (1 mcg/kg/h) group and a control group (NaCl), which received an equivalent CRI of NaCl. Dogs were premedicated with fentanyl 5 mcg/kg IV, induced with propofol, and maintained with sevoflurane and a variable rate fentanyl infusion. DEX or NaCl infusions were started 10 min prior to induction. Fluid-responsive hypotensive patients received repeated Ringer's lactate boluses (2 mL/kg) until stable or they were no longer fluid-responsive. Patients that remained hypotensive following fluid boluses received norepinephrine at a starting dose of 0.05 mcg/kg/min, with increases of 0.05 mcg/kg/min. Rescue adrenaline boluses were administered (0.001 mg/kg) if normotension was not achieved within 30 min of starting norepinephrine. The NaCl group received a significantly higher dose of norepinephrine (0.8, 0.4-2 mcg/kg/min) than the DEX group (0.12, 0-0.86 mcg/kg/min). Mortality was statistically lower in the DEX group (1/10) vs. the NaCl group (5/6). Results of this study suggest that a 1 mcg/kg/h CRI of dexmedetomidine decreases the demand for intraoperative vasopressors and may improve survival in septic dogs.

Saphenous and Sciatic Nerve Blockade with and without Obturator Nerve Block for Tibial Plateau Levelling Osteotomy Surgery in Dogs: A Randomized Controlled Trial.

The objective of our study was to compare the efficacy of sciatic and saphenous ultrasound nerve blocks with and without US-guided obturator nerve block in dogs undergoing tibial-plateau-levelling-osteotomy (TPLO) surgery. This study was developed in two phases: identification of an ultrasound window in the inguinal region for obturator nerve block and utilization of it in dogs undergoing TPLO. Dogs were assigned randomly to one of two groups: one received the three blocks with 0.5% ropivacaine (ON group) and the second one (NoON group) with NaCl instead of ropivacaine for the obturator block. In phase 1, the obturator nerve was visible between the pectineus and the abductor muscles and was approached using an in-plane technique. It was possible to use the ultrasound window for phase two. The number of dogs that received at least one bolus of intraoperative rescue analgesia in the NoON group (12/15 dogs) was significantly higher (p = 0.003) in comparison with the ON group (4/15). An ultrasound window to block the obturator nerve in the inguinal compartment with an in-plane technique was found. The use of this approach could produce adequate analgesia with less motor function impairment in dogs for TPLO surgery.

Detection of Myositis Autoantibodies by Multi-Analytic Immunoassays in a Large Multicenter Cohort of Patients with Definite Idiopathic Inflammatory Myopathies.

BACKGROUND: The usefulness of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) for the assessment of idiopathic inflammatory myopathies (IIMs) is acknowledged, but laboratory standardization remains a challenge. We detected MSAs/MAAs by multi-analytic line immunoassay (LIA) and particle-based multi-analyte technology (PMAT) in a multicenter cohort of patients with IIMs. METHODS: We tested the sera from 411 patients affected with definite IIM, including 142 polymyositis (PM), 147 dermatomyositis (DM), 19 cancer-associated myositis, and 103 overlap myositis syndrome (OM), and from 269 controls. MSAs/MAAs were determined by 16Ags LIA in all sera, and anti-HMGCR by ELISA in 157/411 IIM sera and 91/269 control sera. The analytical specificity of LIA/HMGCR ELISA was compared with that of PMAT in 89 MSA+ IIM sera. RESULTS: MSAs/MAAs were positive in 307/411 (75%) IIM patients and 65/269 (24%) controls by LIA (Odds Ratio 9.26, 95% CI 6.43-13.13, p < 0.0001). The sensitivity/specificity of individual MSAs/MAAs were: 20%/100% (Jo-1), 3%/99.3% (PL-7), 4%/98.8% (PL-12), 1%/100% (EJ), 0.7%/100% (OJ), 9%/98% (SRP), 5.6%/99.6% (TIF1γ), 4.6%/99.6% (MDA5), 8%/96% (Mi-2), 1.5%/98% (NXP2), 1.7%/100% (SAE1), 4%/92% (Ku), 8.5%/99% (PM/Scl-100), 8%/96% (PM/Scl-75), and 25.5%/79% (Ro52). Anti-HMGCR was found in 8/157 (5%) IIM patients and 0/176 (0%) controls by ELISA (p = 0.007). Concordance between LIA/HMGCR ELISA and PMAT was found in 78/89 (88%) samples. Individual MSAs detected by LIA were associated with IIM subsets: Jo-1 with PM and OM, PL-12 with OM, Mi-2, TIF1γ, and MDA5 with DM, SRP with PM, and PM/Scl-75/100 with OM (p < 0.001 for all). CONCLUSIONS: Since MSAs are mostly mutually exclusive, multi-specific antibody profiling seems effective for a targeted clinical-serologic approach to the diagnosis of IIMs.

Characterization of Serum Cytokine Profiles of Patients with Active Lupus Nephritis.

Cytokines contribute to the pathogenesis of lupus nephritis (LN), yet their value as prognostic biomarkers is still debated. We aimed to describe the serum cytokines' profiles and prospectively assess correlations with disease features and renal response in a multicentric cohort of consecutive adult patients with biopsy-proven active LN. Cytokine associations with clinical and serological data were performed at LN diagnosis (T0), and at 3 (T3) and 6 months (T6) of follow up. Renal response according to EULAR definition was assessed at T3, T6 and T12. BAFF and interleukin (IL)-37 were measured by ELISA; IL-2, IL-10, IL-17A and IL-18 by a bead-based multiplex cytokine assay (Luminex). Thirty-nine patients with active LN (age 40.5 ± 15.6 years; F 71.8%; 84.6% proliferative LN) were enrolled, of whom twenty-nine displayed complete longitudinal records. At T0, we observed higher levels of IL-37 and IL-17 in proliferative vs. non-proliferative LN (IL-37: 0.0510 (0.0110-0.2300) vs. 0.0000 (0.0000-0.0397) ng/mL, p = 0.0441; IL-17: 2.0920 (0.5125-17.9400) vs. 0.0000 (0.0000-0.6025) pg/mL, p = 0.0026, respectively), and positive correlations between IL-10 and 24 h proteinuria (r = 0.416, p = 0.0249) and anti-dsDNA levels (r = 0.639, p = 0.0003). BAFF was higher in patients with low complement (p < 0.0001). We observed a sustained correlation between BAFF and IL-10 throughout T6 (r = 0.654, p = 0.0210). Higher baseline IL-37 and BAFF levels were associated with renal response at T3 and T6, respectively, while baseline IL-18 levels were higher in patients achieving response at T12. Our study highlights the complexity of the cytokine network and its potential value as a marker of active LN and renal response.

Anti-MDA5 dermatomyositis: an update from bench to bedside.

PURPOSE OF REVIEW: This review summarizes the recent developments about anti-MDA5 antibody positive dermatomyositis with a focus on its pathogenesis, clinical features and treatment options of rapidly progressive interstitial lung disease, its most ominous complication. RECENT FINDINGS: Anti-MDA5+ dermatomyositis has a heterogeneous clinical spectrum with different patient subsets exhibiting widely different outcomes; severe acute interstitial lung disease is the main factor impacting prognosis. The pathogenetic role of anti-MDA5 antibodies is an active area of investigation. SUMMARY: Anti-MDA5+ dermatomyositis has a wider spectrum of manifestations than previously thought. A high index of suspicion is needed not to miss atypical presentations. In the setting of acute interstitial lung involvement, once a confident diagnosis is made, an aggressive approach with early combined immunosuppression affords the best chances of survival.

IgG anti-Pentraxin 3 antibodies are a novel biomarker of ANCA-associated vasculitis and better identify patients with eosinophilic granulomatosis with polyangiitis.

OBJECTIVE: To investigate prevalence of anti-Pentraxin 3 (PTX3) antibodies in sera of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients. METHODS: Anti-PTX3 and PTX3 levels were analysed by enzyme-linked immunosorbent assays in sera from unselected patients with AAV and compared with patients with systemic lupus erythematosus (SLE, n = 130), other connective tissue diseases (CTDs, n = 97) and matched healthy controls (n = 97). Optical density (OD) cut-off for positive anti-PTX3 antibodies was determined by ROC curve analysis and set as 0.234. Indirect immunofluorescence (IIF) on fixed human granulocytes was used to analyze the fluorescence pattern of anti-PTX3 antibodies. Liquid-phase inhibition tests were conducted to assess potential interferences. RESULTS: We included 101 AAV patients (females 58%, median age 60[51-69] years) affected either with granulomatosis with polyangiitis (GPA, n = 51), microscopic polyangiitis (MPA, n = 12) or eosinophilic granulomatosis with polyangiitis (EGPA, n = 38). Anti-PTX3 antibodies were detected in 29.7% AAV patients, being significantly higher than in healthy controls (p < 0.001) and CTDs (p = 0.030) but lower than in SLE (p = 0.004). Anti-PTX3 antibody prevalence was 44.7% in EGPA, 25% in MPA and 19% in GPA (p = 0.034). Among ANCA negative patients, 35.7% displayed positive anti-PTX3 antibodies. Anti-PTX3 were associated with a lower prevalence of systemic (p = 0.002), ear-nose-throat (p = 0.006) and renal manifestations (p = 0.016). Anti-PTX3 antibodies were characterized by a specific IIF pattern on fixed granulocytes. PTX3 serum levels resulted lower in AAV than healthy controls (p < 0.001). PTX3 inhibited anti-PTX3 binding in a dose-dependent manner. CONCLUSIONS: Anti-PTX3 autoantibodies appear a promising novel biomarker of AAV, especially EGPA.