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Simple Summary: During the awakening phase from general anesthesia, phases of agitation, excitement, vocalization, or violent movements are present in both human and veterinary medicine. Treatment for this phase involves the administration of sedatives such as alpha-2 agonist drugs that represents an established practice in equine anesthesia recovery. Dexmedetomidine is an alpha-2 agonist with sedative properties commonly used in veterinary clinical practice as a preanesthetic agent. The possibility of preventing these episodes of agitated awakening with the preventive administration of dexmedetomidine in canine patients has been studied in different populations. The objective of our study was to evaluate the quality of recovery from general anesthesia in dogs with the administration of two low doses of intravenous 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Sepsis is a widespread concern in human and veterinary medicine. Over the past several years, numerous strategies have been implemented to try to combat it; however, mortality remains high in all species. The use of dexmedetomidine, an alpha-two agonist drug with sedative and analgesic properties, is gaining popularity as a synergistic treatment strategy in the management of sepsis, thanks to its anti-apoptotic and neuroprotective properties and its ability to preserve hemodynamic function. We therefore hypothesized that a continuous rate infusion of dexmedetomidine in septic patients, undergoing emergency surgery, could decrease the requirement for vasopressors. The results of this study show that an infusion of 1 mcg/kg/h of dexmedetomidine decreases intraoperative vasopressor use and improves 28-day mortality. However, given the small sample size, a larger prospective study should be undertaken to confirm these findings. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Locoregional anaesthesia plays a fundamental role in the correct management of surgical interventions. Veterinary ultrasound-guided techniques are in continuous evolution to obtain adequate analgesia with minimal motor impact. We hypothesized that the block of the obturator nerve in the inguinal compartment, combined with the block of the saphenous and the sciatic nerves, without the block of the femoral nerve, could produce analgesia with less motor function impairment for tibial-plateau-levelling-osteotomy (TPLO) surgery. Having easily identified a window during the anatomical study that included an inguinal approach, we could correctly perform this new ultrasound-guided obturator-nerve-block technique. Patients that received three blocks with ropivacaine had statistically significantly less need for rescue analgesia during surgery than those that received saline solution at the level of the obturator nerve. In the group that did not receive ropivacaine for the obturator nerve block, nociception occurred in almost all patients at the time of incision of the joint capsule, showing the obturator nerve role in the innervation of the knee joint. The use of this new technique in association with the block of the sciatic and saphenous nerves represents an improvement in locoregional techniques in knee surgery, as the patient not only has a reduction in intraoperative nociception but also has better postoperative mobility, resulting from the fact that the femoral nerve, which is responsible for the innervation of the quadriceps muscles, was not blocked. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Laparoscopic ovariectomy is currently considered the gold standard for neutering female dogs thanks to the reduced surgical trauma, lower perioperative pain, and decreased hospitalization stays. Perioperative analgesic management becomes crucial to reduce the occurrence of uncontrolled post-surgery stress response. The quadratus lumborum block is an ultrasound-guided block capable of providing somatic and visceral analgesia to the abdomen. The aims of this study were (I) to evaluate the efficacy of the transversal quadratus lumborum block performed with two different concentrations of ropivacaine (0.5% and 0.33%) in prolonging the time to the first postoperative rescue analgesia in dogs undergoing laparoscopic ovariectomy, in comparison with a fentanyl-based protocol, and (II) to investigate the cardiovascular impact of the block on the arterial blood pressure. The results of this study showed a significantly longer time to the first postoperative rescue analgesia in groups receiving the block, in comparison with the group receiving a fentanyl-based protocol. Surprisingly, ropivacaine 0.33% produce a more important reduction in the arterial blood pressure than ropivacaine 0.5%. Further studies are needed to better assess the intraoperative efficacy of the quadratus lumborum block. The aim of this study was to evaluate the effect of the transverse quadratus lumborum block (QLBLQL-T) on time to the first postoperative rescue analgesia in dogs submitted to laparoscopic ovariectomy. A total of twenty-three female dogs were included. Dogs were randomly assigned to receive a bilateral QLBLQL-T, performed either with 0.3 mL kg−1 ropivacaine 0.5% [group QLB0.5% (n = 8)] or with ropivacaine 0.33% [group QLB0.33% (n = 8)] or a fentanyl-based protocol [group No-QLB (n = 7)]. Dogs were premedicated intravenously (IV) with fentanyl 5 mcg kg−1, general anesthesia was induced IV with propofol and maintained with sevoflurane. Invasive mean arterial pressure (MAP) values were recorded five minutes before and five minutes after performing the QLBLQL-T. The short-form of the Glasgow composite measure pain scale was used every hour after extubation, and methadone 0.2 mg kg−1 was administered IV when pain score was ≥5/24. Kolmogorov–Smirnov test, ANOVA test combined with Tukey post hoc test, Student's T-test and Chi-square test were used to analyze data; p < 0.05. Time from QLBLQL-T to the first rescue analgesia was significantly longer in QLB0.5% than in group QLB0.33% and No-QLB. MAP pre- and post-block decreased significantly only in group QLB0.33%. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

There is still a need for an efficient method for the isolation of extracellular vesicles (EVs) from human blood that provides a reliable yield with acceptable purity. Blood is a source of circulating EVs, but soluble proteins and lipoproteins hamper their concentration, isolation, and detection. This study aims to investigate the efficiency of EV isolation and characterization methods not defined as "gold standard". EVs were isolated from human platelet-free plasma (PFP) of patients and healthy donors through size-exclusion chromatography (SEC) combined with ultrafiltration (UF). Then, EVs were characterized using transmission electron microscopy (TEM), imaging flow cytometry (IFC), and nanoparticle tracking analysis (NTA). TEM images showed intact and roundish nanoparticles in pure samples. IFC analysis detected a prevalence of CD63+ EVs compared to CD9+, CD81+, and CD11c+ EVs. NTA confirmed the presence of small EVs with a concentration of ~1010 EVs/mL that were comparable when stratifying the subjects by baseline demographics; conversely, concentration differed according to the health status across healthy donors and patients affected with autoimmune diseases (130 subjects in total, with 65 healthy donors and 65 idiopathic inflammatory myopathy (IIM) patients). Altogether, our data show that a combined EV isolation method, i.e., SEC followed by UF, is a reliable approach to isolate intact EVs with a significant yield from complex fluids, which might characterize disease conditions early. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are extensively studied as therapeutic tools. Evaluation of their biodistribution is fundamental to understanding MSC-EVs' impact on target organs. In our work, MSC-EVs were initially labeled with DiR, a fluorescent lipophilic dye, and administered to BALB/c mice (2.00 × 1010 EV/mice) through the following routes: intravenous (IV), intratracheal (IT) and intranasal (IN). DiR-labeled MSC-EVs were monitored immediately after injection, and after 3 and 24 hours (h). Whole-body analysis, 3 h after IV injection, showed an accumulation of MSC-EVs in the mice abdominal region, compared to IT and IN, where EVs mainly localized at the levels of the chest and brain region, respectively. After 24 h, EV-injected mice retained a stronger positivity in the same regions identified after 3 h from injection. The analyses of isolated organs confirmed the accumulation of EVs in the spleen and liver after IV administration. Twenty-four hours after the IT injection of MSC-EVs, a stronger positivity was detected selectively in the isolated lungs, while for IN, the signal was confined to the brain. In conclusion, these results show that local administration of EVs can increase their concentration in selective organs, limiting their systemic biodistribution and possibly the extra-organ effects. Biodistribution studies can help in the selection of the most appropriate way of administration of MSC-EVs for the treatment of different diseases. [ABSTRACT FROM AUTHOR]

This article presents the results of a qualitative study aiming to consider the relationship between ambiguous loss and anticipatory mourning amongst relatives of missing people in Italy. Eight people participated in the research, narrating their experiences of losing a beloved person (one found alive, three found dead, and four still missing). Findings suggest the presence of a particular form of ambiguous loss, characterised by traits typical of both prolonged and traumatic grief. These findings describe how families are faced with an emotional vortex related to a never-ending wait, and how the mourning is solved only when the missing person is found dead or alive. The discovery of a corpse is traumatic but it allows mourners to fully recognise their grief. When a person is found, it changes the relationship in a positive way. When neither of these events happen, mourners have two different kinds of reactions: they experience either a prolonged grief or a drive to solve their suffering by helping other people (post-traumatic growth). In this study, it is highlighted how a community can be useful or detrimental in this process, and the importance of psychological and social support to prevent significant clinical outcomes is stressed. [ABSTRACT FROM AUTHOR]