Beneficial effects of recombinant CER-001 high-density lipoprotein infusion in sepsis: results from a bench to bedside translational research project.

BACKGROUND: Sepsis is characterized by a dysregulated immune response and metabolic alterations, including decreased high-density lipoprotein cholesterol (HDL-C) levels. HDL exhibits beneficial properties, such as lipopolysaccharides (LPS) scavenging, exerting anti-inflammatory effects and providing endothelial protection. We investigated the effects of CER-001, an engineered HDL-mimetic, in a swine model of LPS-induced acute kidney injury (AKI) and a Phase 2a clinical trial, aiming to better understand its molecular basis in systemic inflammation and renal function. METHODS: We carried out a translational approach to study the effects of HDL administration on sepsis. Sterile systemic inflammation was induced in pigs by LPS infusion. Animals were randomized into LPS (n = 6), CER20 (single dose of CER-001 20 mg/kg; n = 6), and CER20 × 2 (two doses of CER-001 20 mg/kg; n = 6) groups. Survival rate, endothelial dysfunction biomarkers, pro-inflammatory mediators, LPS, and apolipoprotein A-I (ApoA-I) levels were assessed. Renal and liver histology and biochemistry were analyzed. Subsequently, we performed an open-label, randomized, dose-ranging (Phase 2a) study included 20 patients with sepsis due to intra-abdominal infection or urosepsis, randomized into Group A (conventional treatment, n = 5), Group B (CER-001 5 mg/kg BID, n = 5), Group C (CER-001 10 mg/kg BID, n = 5), and Group D (CER-001 20 mg/kg BID, n = 5). Primary outcomes were safety and efficacy in preventing AKI onset and severity; secondary outcomes include changes in inflammatory and endothelial dysfunction markers. RESULTS: CER-001 increased median survival, reduced inflammatory mediators, complement activation, and endothelial dysfunction in endotoxemic pigs. It enhanced LPS elimination through the bile and preserved liver and renal parenchyma. In the clinical study, CER-001 was well-tolerated with no serious adverse events related to study treatment. Rapid ApoA-I normalization was associated with enhanced LPS removal and immunomodulation with improvement of clinical outcomes, independently of the type and gravity of the sepsis. CER-001-treated patients had reduced risk for the onset and progression to severe AKI (stage 2 or 3) and, in a subset of critically ill patients, a reduced need for organ support and shorter ICU length of stay. CONCLUSIONS: CER-001 shows promise as a therapeutic strategy for sepsis management, improving outcomes and mitigating inflammation and organ damage. TRIAL REGISTRATION: The study was approved by the Agenzia Italiana del Farmaco (AIFA) and by the Local Ethic Committee (N° EUDRACT 2020-004202-60, Protocol CER-001- SEP_AKI_01) and was added to the EU Clinical Trials Register on January 13, 2021.

Cannabinoid Receptors Overexpression in a Rat Model of Irritable Bowel Syndrome (IBS) after Treatment with a Ketogenic Diet.

The administration of a ketogenic diet (KD) has been considered therapeutic in subjects with irritable bowel syndrome (IBS). This study aimed to investigate the molecular mechanisms by which a low-carbohydrate diet, such as KD, can improve gastrointestinal symptoms and functions in an animal model of IBS by evaluating possible changes in intestinal tissue expression of endocannabinoid receptors. In rats fed a KD, we detected a significant restoration of cell damage to the intestinal crypt base, a histological feature of IBS condition, and upregulation of CB1 and CB2 receptors. The diet also affected glucose metabolism and intestinal membrane permeability, with an overexpression of the glucose transporter GLUT1 and tight junction proteins in treated rats. The present data suggest that CB receptors represent one of the molecular pathways through which the KD works and support possible cannabinoid-mediated protection at the intestinal level in the IBS rats after dietary treatment.

Absorbable fixation straps for laparoscopic gastropexy in dogs.

OBJECTIVE: To evaluate the feasibility and efficacy of laparoscopic absorbable fixation straps (AFS) for laparoscopic gastropexy in dogs. STUDY DESIGN: Cadaveric and prospective clinical study. ANIMALS: Five dog cadavers for the cadaveric study; 12 dogs for the clinical study. METHODS: The pyloric antrum was affixed to the abdominal wall laparoscopically by applying a series of straps. The cadaveric study assessed potential challenges during the procedure and stomach mucosal penetration. For the clinical study, the total duration of surgery, time to complete the gastropexy, and the number of straps used were recorded. Ultrasound evidence of adhesion, complications, and weight were monitored at 7, 30, and 90 days after surgery. Owner satisfaction was evaluated at the 6-month follow-up. RESULTS: The total duration of surgery was 25.8 minutes (range, 19-39; SD, 6.7), and the time to complete the gastropexy was 10.1 minutes (range, 7-19; SD, 3.9). The linear regression analysis revealed an inverse correlation between the time to complete the gastropexy and the order of the surgeries (r2  = 0.75, P < .05). No complications were recorded. Ultrasound examination was used to confirm gastropexy at all follow-ups. CONCLUSION: Laparoscopic gastropexy with AFS was performed in both cadavers and clinical animals with minimal complications. Persistent adhesion was demonstrated during ultrasound evaluations and in one postmortem evaluation. CLINICAL SIGNIFICANCE: This novel laparoscopic technique can be employed safely, effectively, and reasonably quickly, and the learning curve is expected to be relatively short.

Iron Overload Mimicking Conditions Skews Bone Marrow Dendritic Cells Differentiation into MHCIIlowCD11c+CD11b+F4/80+ Cells.

Iron overload is an undesired effect of frequent blood transfusions or genetic diseases. Myelodysplastic syndrome (MDS) patients become transfusion dependent, but due to the combination of ineffective haematopoiesis and repeated blood transfusions they are often subject to iron overload. In this study, we demonstrate that iron-overload mimicking condition alters bone marrow progenitor differentiation towards dendritic cells (DCs). Cells cultured in iron-enriched culture medium for seven days fail to differentiate into conventional CD11c+MHCIIhi DCs and fail to efficiently respond to LPS (Lipopolysaccharides). Cells appear smaller than control DCs but vital and able to perform FITC-dextran (Fluorescein isothiocyanate-dextran) endocytosis. At molecular level, cells cultured in iron-enriched conditions show increased ARG1 and PU.1, and decreased IRF8 expression.

Surface glycan pattern of canine, equine, and ovine bone marrow-derived mesenchymal stem cells.

The use of bone marrow-derived mesenchymal stem cells (MSCs) for clinical and experimental studies is increasing, but full characterization of MSCs in veterinary species is hindered by the variability in species-specific cell surface marker expression and antibody cross reactivity. Recent studies demonstrated that the glycans in the glycocalyx of MSCs are promising candidates as cell biomarkers. In the present study, we analyzed the glycocalyx of canine MSCs (cMSCs), ovine MSCs (oMSCs), and equine MSCs (eMSCs) using a cell microarray procedure in which MSCs were spotted on microarray slides and incubated with a panel of 14 biotinylated lectins and Cy3-conjugated streptavidin. The signal intensity was then detected using a microarray scanner. The lectin-binding signals indicated that the MSC surface of the investigated species contained both N- and O-linked glycan types, with N-glycosylation predominating over O-glycosylation and fucosylation being more abundant than sialylation. Relative quantification revealed an interspecific difference between these glycans. In addition, cMSCs expressed more α2,3-linked sialic acid (MAL II), terminal lactosamine (RCA120 ), and α1,6 and α1,3 fucosylated oligosaccharides (PSA, LTA); oMSCs exhibited more T antigen (Jacalin), GalNAcα1,3(LFucα1,2)Galß1,3/4GlcNAcß1 (DBA), chitotriose (succinylated WGA), and α1,2-linked fucose (UEA I); and eMSCs showed a higher density of α2,6 sialic acids (SNA) and high mannose N-glycans (Con A). Using cell microarray methodology, we have for the first time demonstrated differences in the glycosylation profiles of cMSC, oMSC, and eMSC surfaces. These results could be valuable as resources and references for MSC differentiation and molecular remodeling in clinical cell-based therapy and tissue engineering studies. © 2017 International Society for Advancement of Cytometry.

Perioperative analgesic effects of an ultrasound-guided transversus abdominis plane block with a mixture of bupivacaine and lidocaine in cats undergoing ovariectomy.

OBJECTIVE: To evaluate the perioperative analgesic effects of a transversus abdominis plane (TAP) block with a mixture of lidocaine and bupivacaine administered to cats undergoing ovariectomy. STUDY DESIGN: Controlled, randomized, prospective, blinded clinical study. ANIMALS: A group of 20 healthy cats. METHODS: Robenacoxib (2 mg kg-1) was administered subcutaneously 0.5 hour before intramuscular (IM) administration of ketamine (5 mg kg-1), methadone (0.1 mg kg-1) and dexmedetomidine (0.01 mg kg-1). General anesthesia was induced with intravenous (IV) propofol and maintained with isoflurane. An ultrasound-guided TAP block was performed by injecting 0.5% bupivacaine (0.2 mL kg-1) diluted in a total volume of 1.5 mL 2% lidocaine bilaterally (TAP group, n = 10) or the same volume of saline solution bilaterally in controls (CTR group, n = 10). During surgery, a 20% increase in heart rate and respiratory frequency was treated with IV fentanyl (0.001 mg kg-1). Before premedication and at 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 hours after extubation, pain was assessed with a simple descriptive pain scale, that ranged from 0 (no pain) to 4 (intense pain). For pain scores ≥3, IM methadone (0.1 mg kg-1) was administered. Data were analyzed with the Friedman or the analysis of variance (anova) test, and p < 0.05 was considered statistically significant. RESULTS: Only two cats in the CTR group were administered one dose of fentanyl during surgery. At 2, 6, 8, 12, 16, 20 and 24 hours after surgery, the pain score was higher in the CTR group. A mean dose of 0.5 ± 0.2 mg kg-1 methadone was administered to all cats in the CTR groups within 24 hours. Methadone was not administered to the TAP group (pain score < 3). CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasound-guided TAP block can be a reliable adjunctive technique, providing analgesia for up to 24 hours in cats undergoing ovariectomy.

Infiltrating mast cells correlate with angiogenesis in bone metastases from gastric cancer patients.

While gastric cancer is a well established angiogenesis driven tumor, no data has been published regarding angiogenesis stimulated by mast cells (MCs) positive for tryptase in bone metastases from gastric cancer patients (BMGCP). It is well established that MCs play a role in immune responses and more recently it was demonstrated that MCs have been involved in tumor angiogenesis. We analyzed infiltrating MCs and neovascularization in BMGCP diagnosed by histology. A series of 15 stage T3-4N2-3M1 (by AJCC for Gastric Cancer Staging 7th Edition) BMGCP from bone biopsies were selected. Tumour tissue samples were evaluated by mean of immunohistochemistry and image analysis methods in terms of MCs density positive to tryptase (MCDPT), MCs area positive to tryptase (MCAPT), microvascular density (MVD) and endothelial area (EA). A significant correlation between MCDPT, MCAPT, MVD and EA groups to each other was found by Pearson and t-test analysis (r ranged from 0.68 to 0.82; p-value ranged from 0.00 to 0.02). Our very preliminary data suggest that infiltrating MCs positive for tryptase may play a role in BMGCP angiogenesis, and could be further evaluated as a novel target of anti-angiogenic therapy.

Recruitment-to-inflation ratio reflects the impact of peep on dynamic lung strain in a highly recruitable model of ARDS.

BACKGROUND: The recruitment-to-inflation ratio (R/I) has been recently proposed to bedside assess response to PEEP. The impact of PEEP on ventilator-induced lung injury depends on the extent of dynamic strain reduction. We hypothesized that R/I may reflect the potential for lung recruitment (i.e. recruitability) and, consequently, estimate the impact of PEEP on dynamic lung strain, both assessed through computed tomography scan. METHODS: Fourteen lung-damaged pigs (lipopolysaccharide infusion) underwent ventilation at low (5 cmH2O) and high PEEP (i.e., PEEP generating a plateau pressure of 28-30 cmH2O). R/I was measured through a one-breath derecruitment maneuver from high to low PEEP. PEEP-induced changes in dynamic lung strain, difference in nonaerated lung tissue weight (tissue recruitment) and amount of gas entering previously nonaerated lung units (gas recruitment) were assessed through computed tomography scan. Tissue and gas recruitment were normalized to the weight and gas volume of previously ventilated lung areas at low PEEP (normalized-tissue recruitment and normalized-gas recruitment, respectively). RESULTS: Between high (median [interquartile range] 20 cmH2O [18-21]) and low PEEP, median R/I was 1.08 [0.88-1.82], indicating high lung recruitability. Compared to low PEEP, tissue and gas recruitment at high PEEP were 246 g [182-288] and 385 ml [318-668], respectively. R/I was linearly related to normalized-gas recruitment (r = 0.90; [95% CI 0.71 to 0.97) and normalized-tissue recruitment (r = 0.69; [95% CI 0.25 to 0.89]). Dynamic lung strain was 0.37 [0.29-0.44] at high PEEP and 0.59 [0.46-0.80] at low PEEP (p < 0.001). R/I was significantly related to PEEP-induced reduction in dynamic (r = - 0.93; [95% CI - 0.78 to - 0.98]) and global lung strain (r = - 0.57; [95% CI - 0.05 to - 0.84]). No correlation was found between R/I and and PEEP-induced changes in static lung strain (r = 0.34; [95% CI - 0.23 to 0.74]). CONCLUSIONS: In a highly recruitable ARDS model, R/I reflects the potential for lung recruitment and well estimates the extent of PEEP-induced reduction in dynamic lung strain.

In vivo validation of highly customized cranial Ti-6AL-4V ELI prostheses fabricated through incremental forming and superplastic forming: an ovine model study.

Cranial reconstructions are essential for restoring both function and aesthetics in patients with craniofacial deformities or traumatic injuries. Titanium prostheses have gained popularity due to their biocompatibility, strength, and corrosion resistance. The use of Superplastic Forming (SPF) and Single Point Incremental Forming (SPIF) techniques to create titanium prostheses, specifically designed for cranial reconstructions was investigated in an ovine model through microtomographic and histomorphometric analyses. The results obtained from the explanted specimens revealed significant variations in bone volume, trabecular thickness, spacing, and number across different regions of interest (VOIs or ROIs). Those regions next to the center of the cranial defect exhibited the most immature bone, characterized by higher porosity, decreased trabecular thickness, and wider trabecular spacing. Dynamic histomorphometry demonstrated differences in the mineralizing surface to bone surface ratio (MS/BS) and mineral apposition rate (MAR) depending on the timing of fluorochrome administration. A layer of connective tissue separated the prosthesis and the bone tissue. Overall, the study provided validation for the use of cranial prostheses made using SPF and SPIF techniques, offering insights into the processes of bone formation and remodeling in the implanted ovine model.

Pressure-Sensitive Walkway System for Evaluation of Lameness in Dogs Affected by Unilateral Cranial Cruciate Ligament Rupture Treated with Porous Tibial Tuberosity Advancement.

The aim of this study was to objectively evaluate lameness in dogs affected by a unilateral cranial cruciate ligament rupture (CrCLR) treated with porous tibial tuberosity advancement before surgery and at three different timepoints after surgery, using the GAITRite® system (version 4.9Wr), a pressure-sensitive walkway system that is able to calculate several spatiotemporal gait parameters simultaneously for each limb. The dogs walked on the pressure-sensitive walkway before (T0) and 30 (T1), 90 (T2), and 120 (T3) days after surgery. Pressure measurements (gait lameness score and total pressure index %) were collected for S (treated with porous TTA) and C (healthy contralateral limb) at T0, T1, T2, and T3 and statistically evaluated. An ANOVA test was performed to compare the data, and a value of p < 0.05 was considered significant. Twenty dogs (n = 20) of various common breeds and ages with CrCLR were enrolled in the study. The results showed that there was a statistically significant difference in the GAIT4Dog® lameness score (GLS) and TPI% between S and C for each timepoint. Statistically significant differences in the GLS and TPI% between S at T0 and S at T2 and between S at T0 and S at T3 (p < 0.001) were found. The results showed that there was a statistically significant difference in the GAIT4Dog® lameness score (GLS) and TPI% between S and C for each timepoint. Statistically significant differences in the GLS and TPI% between S at T0 and S at T2 and between S at T0 and S at T3 were found. The GLS and TPI% increased statistically significantly from 90 days after surgery compared to the preoperative measurements. Moreover, comparing the GLS and TPI% between the treated limb and the control limb showed that a statistically significant difference remained at each timepoint.

Immune and Inflammatory Response of Donkeys (Equus asinus) Tested Positive to Tick-borne Pathogens.

Among infection diseases transmitted by arthropods, the equine vector-borne diseases transmitted by ticks represent an emerging problem worldwide due to their morbidity and mortality and, in some cases, to their zoonotic relevance. Understanding the host immune/inflammatory response to the pathogens is crucial to develop effective methods of diagnosis, control and treatment. This study aimed to evaluate red blood cells (RBC), hematocrit (Hct), hemoglobin concentration (Hb), mean cell volume (MCV), mean cell hemoglobin content (MCH), mean cell hemoglobin (MCHC), platelets (PLT), white blood cells (WBC), leukocytes populations, and serum protein pattern of Sardinian donkeys scored positive to tick-borne pathogens. Thirty donkeys were dived in five groups, six subjects each: Group 1, tested negative to pathogens (control group); Group 2, donkeys infected by Theileria equi; Group 3, donkeys infected by Ehrlichia equi; Group 4, donkeys infected by Rickettsia Rickettsii; Group 5, donkeys co-infected by T. equi, E. equi and R. Rickettsii. From donkeys blood samples were collected and haematological and serum protein profiles were assessed. One-way ANOVA showed lower red blood cells, haemoglobin, platelets, lymphocytes and neutrophils values, and higher eosinophils, basophils, serum total proteins, α2-, ß- and γ- globulins values in donkeys infected by one or more pathogens compared to control group (P < .05). The study highlighted an immune and inflammatory response of donkeys positive to E. equi, T. equi, and R. Rickettsii and represents a starting point for further investigations in the field to fill the gaps currently existing on the complex interwoven relationship between the pathogen and host immune and inflammatory response in equids.

Retrospective study of lameness in beef cattle in northeastern Sardinia, Italy.

Lameness is one of the most prevalent diseases affecting dairy and beef cattle, resulting in decreased animal performance, decreased animal welfare, and substantial economic loss. In extensive beef cattle farming, the risk factors for this multifactorial disease are largely unexplored. This study aims to conduct a preliminary epidemiological survey of risk factors in beef cattle in extensive breeding, evaluate the farmer's perception of lameness, and determine the recurrence frequency of the pathologies under investigation in treated animals. The study was conducted in Sardinia, Italy. The population of the study consisted of 14379 cattle from 230 farms. An ad hoc questionnaire was developed to collect all the necessary data. A strong association was found between breed and the occurrence and recurrence of lameness (p < 0.0001). In addition, the Country of origin of both bulls and cows was found to be correlated with the incidence of lameness (p < 0.0001 and 0.0001, respectively). Farmers who indicated on the questionnaire that lameness was not important on their farm had more animals with recurrences (p < 0.0001) than other farmers. The veterinarian's treatment choice differed significantly by farmer concern (p = 0.007) and was associated with less disease recurrence (p < 0.0001), resulting in greater farmer satisfaction (p < 0.007). Pure cow breed, French bull origin, and farmer's age were detected as significant predictors of lameness issues, with pure cow breed and French bull origin having the strongest associations (p = 0.009). Even though the results of this study are preliminary, they indicate that breed selection is crucial in extensive beef farms to reduce lameness prevalence. In addition, it would be reasonable to train breeders to prevent and diagnose lameness early in order to collaborate with veterinarians to prevent recurrence.

Ex-Vivo Evaluation of "First Tip Closing" Radiofrequency Vessel Sealing Devices for Swine Small Intestinal Transection.

This study compared burst pressure (BP), number of activations, and histological assessment of ex vivo swine small intestine loops transected by stapler, a single fulcrum radiofrequency vessel sealing (RFVS) device, and the newly-developed jaws RFVS. Fifty (n = 50) 20 cm long jejunal loops were randomly assigned to be transected with RFVS devices and linear stapler (Caiman5, Caiman Maryland, Caiman12, Ligasure Atlas, and Stapler group as control respectively). Caiman5, Caiman12 and stapler required only one activation to complete the sealing. The mean BP in Caiman5 and Caiman Maryland groups were significantly lower (p < 0.05) than the S group as control and the other RFVS devices studied. RFVS Caiman12 and Ligasure Atlas produced mean BP values that were close to the Control and did not differ between them. The lumen was totally closed in the Caiman12 and Ligasure Atlas groups. The findings of this investigation were promising; we discovered that Caiman12 and Ligasure Atlas produce comparable mechanical capabilities as well as stapled intestinal closure, however Caiman12 need a single activation to complete the transection.

Wound Retractor Laparoscopic Port System for Laparoscopic Ovariectomy in Panthera leo.

The aim of this study was to assess the feasibility and intraoperative complications of performing ovariectomies in African lionesses (Panthera leo) using a wound retractor laparoscopic platform. Six lionesses (n = 6) were included. The surgical procedures were carried out through three portals, with a retractor platform positioned at the umbilical port and cannulas placed 3-4 cm from the cranial and caudal regions to the device at the level of the midline. An ovariectomy was performed with a vessel-sealing device. We evaluated the surgery time and the intraoperative and early postoperative complications. The mean weight was 172.83 kg. The total surgery time was 49.33 min. The installation step took a mean of 10.33 min to complete. The mean ovariectomy time was 20 min. Controlled bleeding was observed at the tip of the uterine horn in two cases due to excessive tissue thickness. The retrieval of dissected ovarian tissue and annexes was easily performed. No other complications were observed. The use of the laparoscopic platform during three-portal surgeries for laparoscopic ovariectomy in adult overweight lionesses is feasible and without intraoperative problems. The retractor meant that there were no entry-related issues due to the 25 mm mini-laparotomy. It also made it simpler to extract thick ovaries and promptly re-establish the pneumoperitoneum.

Effects of two alveolar recruitment maneuvers in an "open-lung" approach during laparoscopy in dogs.

Objectives: The aim of this study was to compare the effects of a sustained inflation alveolar recruiting maneuver (ARM) followed by 5 cmH2O of PEEP and a stepwise ARM, in dogs undergoing laparoscopic surgery. Materials and methods: Twenty adult dogs were enrolled in this prospective randomized clinical study. Dogs were premedicated with methadone intramuscularly (IM); anesthesia was induced with propofol intravenously (IV) and maintained with inhaled isoflurane in pure oxygen. The baseline ventilatory setting (BVS) was as follows: tidal volume of 15 mL/kg, inspiratory pause of 25%, inspiratory to expiratory ratio of 1:2, and the respiratory rate to maintain the end-tidal carbon dioxide between 45 and 55 mmHg. 10 min after pneumoperitoneum, randomly, 10 dogs underwent sustained inflation ARM followed by 5 cmH2O of PEEP (ARMi), while 10 dogs underwent a stepwise recruitment maneuver followed by the setting of the "best PEEP" (ARMc). Gas exchange, respiratory system mechanics, and hemodynamic were evaluated before the pneumoperitoneum induction (BASE), 10 min after the pneumoperitoneum (PP), 10 min after the recruitment (ARM), and 10 min after the pneumoperitoneum resolution (PostPP). Statistical analysis was performed with the ANOVA test (p < 0.05). Results: Static compliance decreased in both groups at PP (ARMc = 1.35 ± 0.21; ARMi = 1.16 ± 0.26 mL/cmH2O/kg) compared to BASE (ARMc = 1.78 ± 0.60; ARMi = 1.66 ± 0.66 mL/cmH2O/kg) and at ARM (ARMc = 1.71 ± 0.41; ARMi = 1.44 ± 0.84 mL/cmH2O/kg) and PostPP (ARMc = 1.75 ± 0.45; ARMi = 1.89 ± 0.59 mL/cmH2O/kg), and it was higher compared to PP and similar to BASE. The PaO2/FiO2, in both groups, was higher at ARM (ARMc = 455.11 ± 85.90; ARMi = 505.40 ± 31.70) and PostPP (ARMc = 521.30 ± 66.20; ARMi = 450.90 ± 70.60) compared to PP (ARMc = 369.53 ± 49.31; ARMi = 394.32 ± 37.72). Conclusion and clinical relevance: The two ARMs improve lung function in dogs undergoing laparoscopic surgery similarly. Application of PEEP at the end of the ARMs prolonged the effects of the open-lung strategy.

Comparison of total laparoscopic gastropexy with the Ethicon Securestrap fixation device versus knotless barbed suture in dogs.

BACKGROUND: This study evaluated the feasibility and efficacy of a laparoscopic absorbable fixation device (Securestrap) in total laparoscopic gastropexy in dogs susceptible to gastric dilatation-volvulus (GDV) compared to laparoscopic gastropexy performed with a barbed suture. We hypothesised that both techniques provide suitable gastropexy. METHODS: The gastropexy was performed by straps (TLG-SS group, n = 6) or with a barbed suture (TLG-Vloc group, n = 6). The total surgery time, gastropexy time, the number of straps used and suture bites were recorded. Clinical and ultrasound investigations were performed during follow-up. RESULTS: The total surgery time was 30 minutes in the TLG-SS, while it was 46.66 minutes in the TLG-Vloc. In the TLG-SS group, gastropexy time was 13 minutes, while 36.3 minutes in the TLG-Vloc. The number of straps employed in TLG-SS was 9, while seven bites were employed in TLG-Vloc. Linear regression analysis of gastropexy time versus the number of procedures was highly correlated (r2 = 0.84) in the TLG-SS. Complications, clinical and ultrasound findings did not differ between the two techniques at 90 days post-surgery. CONCLUSION: TLG-SS laparoscopic technique can be employed safely and effectively in less time and is associated with a relatively short learning curve, which could encourage the widespread use of prophylactic laparoscopic gastropexy.

Swine Small Intestine Sealing Performed by Different Vessel Sealing Devices: Ex-Vivo Test.

This study aimed to evaluate the sealing quality of swine small intestine using different laparoscopic radiofrequency vessel sealing devices (two 5 mm: RFVS-1 and -2; one 10 mm: RFVS-3) and a harmonic scalpel (HS) compared to golden standard closure technique. The study was divided into two arms. In study arm 1: n = 50 swine intestinal loops (10 per group) were transected with each instrument and the loops in which the devices provided complete sealing, at the gross inspection, were tested for maximum burst pressure (BP) and histological evaluation and compared to an automatic linear stapler. After the BP tests, the devices that achieved significantly lower BP values were excluded from the second arm. The RFVS-1 and -3 provided statistically significant results and were used in study arm 2, to obtain full-thickness biopsies along the antimesenteric border of the loop and were compared with hand-sewn intestinal closure (n = 30; 10 per group). The biopsies were histologically evaluated for thermal injury and diagnostic features, and intestinal loops tested for BP. RFVS-3 achieved comparable results (69.78 ± 4.23 mmHg, interquartile range (IQR) 5.8) to stapler closing technique (71.09 ± 4.22 mmHg, IQR 4.38; p > 0.05), while the RFVS-1 resulted in significantly (p < 0.05) lower BP (45.28 ± 15.23 mmHg, IQR 24.95) but over the physiological range, conversely to RFVS-2 (20.16 ± 7.19 mmHg, IQR 12.02) and HS (not measurable). RFVS-3 resulted not significantly different (p > 0.05) (45.09 ± 8.75 mmHg, IQR 10.48) than Suture (35.71 ± 17.51 mmHg, IQR 23.77); RFVS-1 resulted significantly lower values (23.96 ± 10.63 mmHg, IQR 9.62; p < 0.05). All biopsies were judged diagnostic. Data confirmed that RFVS-1 and -3 devices provided suitable intestinal sealing, with BP pressures over the physiological range. Conversely, the HS and RFVS-2 should not be considered for intestinal sealing. RFVS devices could be employed to obtain small intestine stump closure or full-thickness biopsies. However, further studies should be performed in live animals to assess the role of the healing process.

Autologous Bone Marrow Mononuclear Cells (BMMCs) for the Treatment of Uncomplicated Grade 2 Ununited Anconeal Process (UAP) in Six Dogs: Preliminary Results.

The aim of this study was to report the results of autologous bone marrow mononuclear cell (BMMC) transplantation as a minimally invasive treatment for grade 2 UAP in dogs. This was an observational case series on six German shepherd dogs affected by grade 2 UAP as defined according to their clinical condition as well as radiographic and CT findings. Bone marrow was collected from the iliac crest and the mononuclear fraction was separated with density gradient centrifugation. Cells were suspended in fibrin glue before BMMC administration and implanted via transcutaneous injection under IB or CT guidance, using a spinal needle directly inserted into the ossification centre between the anconeal process and the olecranon. Clinical and radiographic follow-up was performed for up to 6 months. Microradiographic assessment was performed on one dog that died of other causes. A progressive reduction of pain within 3 weeks after BMMC administration was observed in all dogs, with gradually increased weight bearing on the affected limb. Radiographic and CT follow-up revealed the progressive fusion of the ossification centre at 90 days without any signs of secondary OA. The examination of microradiographs showed newly formed bone tissue in which a residue of calcified cartilage was present at the site of BMMC implantation. On the basis of these results, BMMC therapy for grade 2 UAP may be considered to be an effective and minimally invasive treatment option for dogs.

Effects of continuous positive airway pressure administered by a helmet in cats under general anaesthesia.

OBJECTIVES: The aim of this study was to evaluate the respiratory effects of non-invasive continuous positive airway pressure (CPAP) administered by a helmet in healthy cats under anaesthesia. METHODS: Fifteen healthy male cats scheduled for castration were anaesthetised with medetomidine (20 µg/kg), ketamine (10 mg/kg) and buprenorphine (20 µg/kg) intramuscularly. When an adequate level of anaesthesia was achieved, a paediatric helmet was placed on all subjects. The helmet was connected to a Venturi valve supplied with medical air and cats received the following phases of treatments: 0 cmH2O (pre-CPAP), 5 cmH2O (CPAP) and 0 cmH2O (post-CPAP). Each treatment lasted 10 mins. At the end of each phase an arterial blood sample was drawn. The following data were also collected: mean arterial pressure, respiratory rate, heart rate and the anaesthesia level score (0 = awake, 10 = deep anaesthesia). The alveolar to arterial oxygen gradient (P[A-a]O2) and the venous admixture (Fshunt) were also estimated. Data were analysed with two-way ANOVA (P <0.05). RESULTS: The arterial partial pressure of oxygen was higher (P <0.001) at CPAP (103.2 ± 5.1 mmHg) vs pre-CPAP (77.5 ± 7.4 mmHg) and post-CPAP (84.6 ± 8.1 mmHg). The P(A-a)O2 and the Fshunt were lower (P <0.001) at CPAP (4.4 ± 2.3 mmHg; 7.4 ± 3.1%) vs pre-CPAP (18.9 ± 6.4 mmHg; 22.8 ± 4.6%) and post-CPAP (15.6 ± 7.3 mmHg; 20.9 ± 4.6 %). No other parameters differed between groups. CONCLUSIONS AND RELEVANCE: Non-invasive CPAP applied by a helmet improves oxygenation in cats under injectable general anaesthesia.

Pentraxin-3-mediated complement activation in a swine model of renal ischemia/reperfusion injury.

Pentraxins are a family of evolutionarily conserved pattern recognition molecules with pivotal roles in innate immunity and inflammation, such as opsonization of pathogens during bacterial and viral infections. In particular, the long Pentraxin 3 (PTX3) has been shown to regulate several aspects of vascular and tissue inflammation during solid organ transplantation. Our study investigated the role of PTX3 as possible modulator of Complement activation in a swine model of renal ischemia/reperfusion (I/R) injury. We demonstrated that I/R injury induced early PTX3 deposits at peritubular and glomerular capillary levels. Confocal laser scanning microscopy revealed PTX3 deposits co-localizing with CD31+ endothelial cells. In addition, PTX3 was associated with infiltrating macrophages (CD163), dendritic cells (SWC3a) and myofibroblasts (FSP1). In particular, we demonstrated a significant PTX3-mediated activation of classical (C1q-mediated) and lectin (MBL-mediated) pathways of Complement. Interestingly, PTX3 deposits co-localized with activation of the terminal Complement complex (C5b-9) on endothelial cells, indicating that PTX3-mediated Complement activation occurred mainly at the renal vascular level. In conclusion, these data indicate that PTX3 might be a potential therapeutic target to prevent Complement-induced I/R injury.