Short-Term Effects of Two COX-2 Selective Non-Steroidal Anti-Inflammatory Drugs on the Release of Growth Factors and Cytokines from Canine Platelet-Rich Gel Supernatants.

(1) Background: There is a lack of knowledge about how a single dose of COX-2 selective non-steroidal anti-inflammatory drugs (NSAIDs) might affect the release of growth factors (GFs) and cytokines from canine platelet-rich gels (PRGs) and other hemocomponents. (2) Methods: A crossover study was conducted in six adult mongrel dogs. Animals were randomized to receive a single dose of either carprofen or firocoxib. PRG, temperature-induced platelet lysate (TIPL), chemically induced PL (CIPL), and plasma hemocomponents were obtained from each dog before (1 h) and after (6 h) the treatments. Platelet and leukocyte counts and determination of the concentrations of platelet-derived growth factor-BB, (PDGF-BB), transforming growth factor beta-1 (TGF-ß1), interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α) and IL-10 concentrations were assayed by ELISA in all hemocomponents. (3) Results: Both platelet and leukocyte counts and PDGF-BB concentrations were not affected by NSAIDs and time. Total TGF-ß1 concentrations were not affected by NSAIDs; however, the release of this GF was increased in PRG supernatants (PRGS) at 6 h. IL-1ß and TNF-α concentrations were significantly (p < 0.001) lower in both firocoxib PRGS and plasma at 6 h, respectively. IL-10 concentrations were significantly (p < 0.001) lower at 6 h in all hemocomponents treated with both NSAIDs. (4) Conclusions: The clinical implications of our findings could indicate that these drugs should be withdrawn from patients to allow their clearance before the clinical use of PRP/PRG. On the other hand, the prophylactic use of NSAIDs to avoid the inflammatory reactions that some patients might have after PRP/PRG treatment should be performed only in those animals with severe reactive inflammation to the treatment.

Comparison of Two Methods for the Measurement of Blood Plasma and Capillary Blood Glucose in Tropical Highland Grassing Dairy Cows.

(1) Background: There is lack of published studies validating specific cow-side glucometers such as Centrivet GK (CVGK). (2) Methods: The aims were (1) to measure and compare the blood glucose concentrations in 52 tropic highland grassing cows by using CVGK and the traditional enzymatic/photometric assay (EPA) in plasma and serum (reference method) and (2) to establish if glucose concentrations obtained via these methods could be affected by several demographic and zootechnical parameters of the dairy herd evaluated. (3) Results: Glucose concentrations were significantly (p = 0.00) affected by the method used for their measurement. The intra-assay coefficient of variation (CV) for glucose concentrations in plasma EPA and for CVGK was 14% for both methods with serum EPA, whereas the inter-assay CV for plasma EPA and CVGK was 8% and 13.7%, respectively, with serum EPA. Pearson correlation coefficient calculations between the reference method in serum and plasma presented a slightly positive significant (p = <0.000) correlation (r = 0.56), whereas there was not a significant (p = 0.413) correlation between serum EPA and CVGK (r = 0.135). The Passing and Bablok regressions were out of the ideal expected values for the slope (ß = 1) and the intercept (α = 0) (11), whereas the Bland-Altman plots showed a bias of 5.29 ± 11.73 (mg/dL) for serum and plasma and 11.01 ± 15.74 (mg/dL) for serum and CVGK. The ROC curve showed no sensitivity in detecting normoglycemic cows (area = 53.7 %, e.d = 12.5 %, p = 0.759) for CVGK when compared to plasma EPA (area = 36.1 %, e.d = 14.2 %, p = 0.256). Plasma EPA exhibited a better but not significant effect in detecting hyperglycemic cows (area = 63.9%, e.d = 14.2%, p = 0.256) when compared to HHD (area = 46.3 %, e.d = 12.5 %, p = 0.759). General glucose concentrations, independently of the method used, were significantly (p = <0.001) greater in young cows when compared to adult and old cows. (4) Conclusions: Glucose concentration measurement in plasma by using EPA or in capillary blood via CVGK were not reliable methods when compared with the reference method.

Endoscopia urgente frente a endoscopia precoz: ¿tiene algún papel la endoscopia urgente en la hemorragia digestiva alta aguda no varicosa? / Urgent endoscopy versus early endoscopy: Does urgent endoscopy play a role in acute non-variceal upper gastrointestinal bleeding?

Introducción: Las principales guías de práctica clínica recomiendan la realización de endoscopia dentro de las 24horas posteriores a la admisión en urgencias en pacientes con hemorragia digestiva alta no variceal. Sin embargo, es un margen de tiempo muy amplio y el papel de la endoscopia urgente (<6horas) es controvertido. Material y métodos: Estudio prospectivo observacional realizado en Hospital Universitario La Paz, donde son seleccionados todos los pacientes, desde el 1 de enero de 2015 hasta el 30 de abril de 2020, que acudieron a urgencias y fueron sometidos a endoscopia por sospecha de hemorragia digestiva alta. Se establecieron dos grupos de pacientes: endoscopia urgente (<6horas) y precoz (6-24horas). El objetivo primario del estudio fue la mortalidad a los 30días. Resultados: Un total de 1.096 pacientes fueron incluidos, de los cuales 682 fueron sometidos a endoscopia urgente. La mortalidad a los 30 días fue del 6% (5% vs 7,7%, p=0,064) y del resangrado fue del 9,6%. No hubo diferencias estadísticamente significativas en la mortalidad, resangrado, necesidad de tratamiento endoscópico, cirugía y/o embolización, pero sí en la necesidad de transfusión (57,5% vs 68,4%, p<0,001) y el número de concentrados de hematíes transfundidos (2,85±4,01 vs 3,51±4,09, p=0,008). Conclusión: La endoscopia urgente, en pacientes con hemorragia digestiva alta aguda, también el subgrupo de alto riesgo (GBS ≥ 12), no se asoció con una mortalidad menor a los 30 días que la endoscopia precoz. Sin embargo, en los pacientes con lesiones endoscópicas de alto riesgo (Forrest I-IIB), fue un predictor significativo de menor mortalidad. Por lo tanto, se requieren más estudios para la identificación correcta de pacientes, que se beneficien de esta actitud médica (endoscopia urgente). (AU)

Introduction: The main clinical practice guidelines recommend endoscopy within 24hours after admission to the Emergency Department in patients with non-variceal upper gastrointestinal bleeding. However, it is a wide time frame and the role of urgent endoscopy (<6hours) is controversial. Material and methods: Prospective observational study carried out at La Paz University Hospital, where all patients were selected, from January 1, 2015 to April 30, 2020, who attended the Emergency Room and underwent endoscopy for suspected upper gastrointestinal bleeding. Two groups of patients were established: urgent endoscopy (<6hours) and early endoscopy (6-24hours). The primary endpoint of the study was 30-day mortality. Results: A total of 1096 were included, of whom 682 underwent urgent endoscopy. Mortality at 30days was 6% (5% vs 7.7%, P=.064) and rebleeding was 9.6%. There were no statistically significant differences in mortality, rebleeding, need for endoscopic treatment, surgery and/or embolization, but there were differences in the necessity for transfusion(57.5% vs 68.4%, P<.001) and the number of concentrates of transfused red blood cells (2.85±4.01 vs 3.51±4.09, P=.008). Conclusion: Urgent endoscopy, in patients with acute upper gastrointestinal bleeding, as well as the high-risk subgroup (GBS ≥12), was not associated with lower 30-day mortality than early endoscopy. However, urgent endoscopy in patients with high-risk endoscopic lesions (ForrestI-IIB), was a significant predictor of lower mortality. Therefore, more studies are required for the correct identification of patients who benefit from this medical approach (urgent endoscopy). (AU)

Urgent endoscopy versus early endoscopy: Does urgent endoscopy play a role in acute non-variceal upper gastrointestinal bleeding? / Endoscopia urgente frente a endoscopia precoz: ¿tiene algún papel la endoscopia urgente en la hemorragia digestiva alta aguda no varicosa?

INTRODUCTION: The main clinical practice guidelines recommend endoscopy within 24hours after admission to the Emergency Department in patients with non-variceal upper gastrointestinal bleeding. However, it is a wide time frame and the role of urgent endoscopy (<6hours) is controversial. MATERIAL AND METHODS: Prospective observational study carried out at La Paz University Hospital, where all patients were selected, from January 1, 2015 to April 30, 2020, who attended the Emergency Room and underwent endoscopy for suspected upper gastrointestinal bleeding. Two groups of patients were established: urgent endoscopy (<6hours) and early endoscopy (6-24hours). The primary endpoint of the study was 30-day mortality. RESULTS: A total of 1096 were included, of whom 682 underwent urgent endoscopy. Mortality at 30days was 6% (5% vs 7.7%, P=.064) and rebleeding was 9.6%. There were no statistically significant differences in mortality, rebleeding, need for endoscopic treatment, surgery and/or embolization, but there were differences in the necessity for transfusion(57.5% vs 68.4%, P<.001) and the number of concentrates of transfused red blood cells (2.85±4.01 vs 3.51±4.09, P=.008). CONCLUSION: Urgent endoscopy, in patients with acute upper gastrointestinal bleeding, as well as the high-risk subgroup (GBS ≥12), was not associated with lower 30-day mortality than early endoscopy. However, urgent endoscopy in patients with high-risk endoscopic lesions (ForrestI-IIB), was a significant predictor of lower mortality. Therefore, more studies are required for the correct identification of patients who benefit from this medical approach (urgent endoscopy).

Leveling Up the Access to Radiation Therapy in Latin America: Economic Analysis of Investment, Equity, and Inclusion Opportunities Up to 2030.

PURPOSE: Latin America faces a shortage in radiation therapy (RT) units and qualified personnel for timely and high-quality treatment of patients with cancer. Investing in equitable and inclusive access to RT over the next decade would prevent thousands of deaths. Measuring the investment gap and payoff is necessary for stakeholder discussions and capacity planning efforts. METHODS AND MATERIALS: Data were collected from the International Atomic Energy Agency's Directory of Radiotherapy Centers, industry stakeholders, and individual surveys sent to national scientific societies. Nationwide data on available devices and personnel were compiled. The 10 most common cancers in 2020 with RT indication and their respective incidence rates were considered for gap calculations. The gross 2-year financial return on investment was calculated based on an average monthly salary across Latin America. A 10-year cost projection was calculated according to the estimated population dynamics for the period until 2030. RESULTS: Eleven countries were included in the study, accounting for 557,213,447 people in 2020 and 561 RT facilities. Approximately 1,065,684 new cancer cases were diagnosed, and a mean density of 768,469 (standard deviation ±392,778) people per available unit was found. By projecting the currently available treatment fractions to determine those required in 2030, it was found that 62.3% and 130.8% increases in external beam RT and brachytherapy units are needed from the baseline, respectively. An overall regional investment of approximately United States (US) $349,650,480 in 2020 would have covered the existing demand. An investment of US $872,889,949 will be necessary by 2030, with the expectation of a 2-year posttreatment gross return on investment of more than US $2.1 billion from patients treated in 2030 only. CONCLUSIONS: Investment in RT services is lagging in Latin America in terms of the population's needs. An accelerated outlay could save additional lives during the next decade, create a self-sustaining system, and reduce region-wide inequities in cancer care access. Cash flow analyses are warranted to tailor precise national-level intervention strategies.

Temporal Release and Denature of Several Mediators in Pure Platelet-Rich Plasma and Temperature-Induced Platelet Lysates Derived from a Similar Bovine Platelet Concentrate.

There is scarce information about bovine platelet-rich plasma/platelet-rich gel (PRP/PRG) and related hemocomponents (HCs), such as platelet lysates (PLs), including growth factor (GF) and cytokine concentrations, and how the stability of these biomolecules could be affected by time and temperature. This study aimed to evaluate the release and stability of transforming growth factor beta 1 (TGF-ß 1), interleukin 4 (IL-4), and tumor necrosis factor alpha (TNF-α) contained in bovine pure PRP (P-PRP) and temperature-induced PL (TIPL) coming from a similar platelet concentrate (PC) at 4 and 37°C at 3 and 96 h. Platelet concentrates (PCs) presented a 1.7-fold concentration of platelets (PLTs) with negligible counts of white blood cells (WBCs) when compared to the counts for these cells in whole blood. TGF-ß 1 concentrations were significantly lowest in plasma followed by TIPL, chemical-induced PL (CIPL), and P-PRP. IL-4 and TNF-α concentrations did not differ between HCs. TGF-ß 1 concentrations were negatively affected in P-PRPs stored at 4°C at 3 and 96 h, whereas those from P-PRP maintained at 37°C presented similar concentrations to TIPL stored at both temperatures over time. IL-4 and TNF-α concentrations were not affected by time or temperature in any of the HCs evaluated. Pure PRGs released additional quantities of GF and cytokines over time when compared with HCs stored over 96 h at 4 and 37°C. The method, either chemical or physical, used for platelet activation or damage produces a different GF and cytokine release pattern, which makes to each evaluated HCs different despite they come from a similar bovine PC. P-PRP activated with calcium gluconate and maintained at 37°C, which polymerizes in P-PRG, showed the best GF and cytokine release/denature profile compared with the rest of the HCs evaluated.

Evaluation of the Pro-, Anti-Inflammatory, and Anabolic Effects of Autologous Platelet-Rich Gel Supernatants in an in vitro Coculture System of Canine Osteoarthritis.

There are scarce in vitro studies indicating the basic mechanisms of why platelet-rich plasma (PRP) is useful in the clinical management of dogs with naturally occurring OA. Methods. Cartilage and synovial membrane explants from six dogs were challenged with lipopolysaccharide (LPS) and cultured for 48 h with platelet-poor gel supernatant (PPGS) and platelet-rich gel supernatant (PRGS) at concentrations of 25 and 50%, respectively. The tissue explants challenged with LPS were cocultured over 48 h and culture media were sampled at 1 and 48 h for the determination of IL-1ß, IL-10, hyaluronan, TGF-ß1, and PDGF-BB by ELISA. Results. IL-1ß concentrations were significantly higher in tissue explant groups cultured for 48 h with PRGS at 50% and with PPGS at 25% when compared to the remaining experimental groups at any time. IL-10 and HA presented similar concentrations in all evaluated groups at any time. TGF-ß1 and PDGF-BB presented higher concentrations in the culture media of tissue explants cultured with PPGS and PRGS at 50%, which diminished with time. Conclusions. Both PPGS and PRGS at both concentrations showed a limited biological effect on cartilage and synovial membrane explants in coculture with LPS. Even PPGS at 25% and PRGS at 50% exhibited proinflammatory effects on these tissues at 48 h.

Correlación entre la endoscopia y la ecografía intestinal para la evaluación de la recurrencia posquirúrgica de la enfermedad de Crohn / Correlation between endoscopy and intestinal ultrasound for the evaluation of postoperative recurrence of Crohn's disease

Objetivo: La ecografía intestinal se considera una alternativa para la evaluación de la recurrencia posquirúrgica (RPQ) de la enfermedad de Crohn. El objetivo de este estudio es evaluar la correlación entre los hallazgos ecográficos y endoscópicos.Métodos: Se recogieron de forma retrospectiva los datos de pacientes con enfermedad de Crohn y resección ileocecal en los que se había realizado una colonoscopia y una ecografía intestinal para la detección de RPQ. La RPQ se evaluó empleando el índice de Rutgeerts (IR). Los hallazgos ecográficos analizados fueron el grosor de la pared intestinal, la hiperemia parietal por Doppler, la desestructuración del patrón de capas y la proliferación fibrograsa.Resultados: Se incluyó a un total de 31 pacientes, 15 (48,4%) sin recurrencia (IR? mm vs. 5,68mm; p?<0,001). La hiperemia también se asoció de forma significativa con la recurrencia endoscópica (p?=?0,03). Para el grosor parietal se obtuvo un área bajo la curva ROC (AUC) del 92,9% y, con punto de corte en 3,4mm, la sensibilidad fue del 100% y la especificidad del 86,6%. Al comparar con los biomarcadores principales (calprotectina fecal y PCR sérica) se obtuvo un AUC superior para el grosor (72,3% y 72,3% vs. 92,9%).Conclusiones: En nuestra experiencia, la ecografía tiene una alta rentabilidad diagnóstica para la detección de RPQ y puede considerarse en muchas ocasiones como una alternativa válida y no invasiva a la ileocolonoscopia.

Objective: Intestinal ultrasound is considered to be a valid alternative for the evaluation of post-operative recurrence (POR) of Crohn's disease. The aim of this study is to assess the correlation between ultrasound and endoscopic findings.Methods: Patients with Crohn's disease were retrospectively recruited who had undergone ileocecal resection, and for whom a colonoscopy and intestinal ultrasound had been performed for the detection of POR. Recurrence was assessed using the Rutgeerts score (RS). The ultrasound findings analysed were bowel wall thickness (BWT), parietal hyperaemia using power Doppler, loss of layer pattern and mesenteric fat hypertrophy.Results: A total of 31 patients were included, of which 15 (48.4%) had no POR (RS<2b) and 16 (51.6%) had POR (RS≥2b). A statistically significant association was identified between BWT and the presence of endoscopic recurrence (a mean of 2.75mm vs. 5.68mm, P>0.001). There was also a statistically significant difference in hyperaemia between the 2groups (P=0.03). For wall thickness, an area under the ROC curve (AUC) of 92.9% was obtained, and with a cut-off point of 3.4mm, a sensitivity of 100% and specificity of 86.6%. When comparing with the most frequent biomarkers (fecal calprotectin and serum CRP), a higher AUC was obtained for wall thickness (72.3% and 72.3% vs. 92.9%).Conclusions: In our experience, ultrasound has high diagnostic efficacy in the detection of POR and can be considered a valid non-invasive alternative to endoscopy.

Correlation between endoscopy and intestinal ultrasound for the evaluation of postoperative recurrence of Crohn's disease. / Correlación entre la endoscopia y la ecografía intestinal para la evaluación de la recurrencia posquirúrgica de la enfermedad de Crohn.

OBJECTIVE: Intestinal ultrasound is considered to be a valid alternative for the evaluation of post-operative recurrence (POR) of Crohn's disease. The aim of this study is to assess the correlation between ultrasound and endoscopic findings. METHODS: Patients with Crohn's disease were retrospectively recruited who had undergone ileocecal resection, and for whom a colonoscopy and intestinal ultrasound had been performed for the detection of POR. Recurrence was assessed using the Rutgeerts score (RS). The ultrasound findings analysed were bowel wall thickness (BWT), parietal hyperaemia using power Doppler, loss of layer pattern and mesenteric fat hypertrophy. RESULTS: A total of 31 patients were included, of which 15 (48.4%) had no POR (RS<2b) and 16 (51.6%) had POR (RS≥2b). A statistically significant association was identified between BWT and the presence of endoscopic recurrence (a mean of 2.75mm vs. 5.68mm, P>0.001). There was also a statistically significant difference in hyperaemia between the 2groups (P=0.03). For wall thickness, an area under the ROC curve (AUC) of 92.9% was obtained, and with a cut-off point of 3.4mm, a sensitivity of 100% and specificity of 86.6%. When comparing with the most frequent biomarkers (fecal calprotectin and serum CRP), a higher AUC was obtained for wall thickness (72.3% and 72.3% vs. 92.9%). CONCLUSIONS: In our experience, ultrasound has high diagnostic efficacy in the detection of POR and can be considered a valid non-invasive alternative to endoscopy.

Intramammary treatment using allogeneic pure platelet-rich plasma in cows with subclinical mastitis caused by Gram-positive bacteria.

The aims of the study were (1) to compare the cure risk of intramammary treatment of pure platelet rich plasma (P-PRP) or cefquinome sulfate (CS) in cows with subclinical mastitis (SCM) caused by Gram-positive bacteria, evaluated via somatic cell count (SCC) and the microbiological analysis of milk; (2) to compare the inflammatory/anti-inflammatory response of mammary gland to both treatments through the analyses of interleukins (IL), interferon gamma (IFN-γ), and tumour necrosis factor alpha (TNF-α) in milk. A non-inferiority randomized clinical trial was conducted. The null hypothesis was that cure risk in the experimental group (P-PRP) was inferior to the reference group (CS). A total of 103 cows were selected according to SCC and presence of Gram-positive bacteria, 49 cows were treated with CS and 54 cows were treated with P-PRP after determination of its cellular and molecular quality control. Cure was assessed by milk analyses at day 21 and 22 after treatment. Cows that remained with SCM were retreated at day 26, and cure assessed at day 47 and 48. Overall, bacteriological cure was observed in 16 cows (30%) of the P-PRP group, and 35 cows (71%) in CS group. Staphylococcus aureus cure risk was higher in CS group, but inconclusive for Streptococcus spp. The mean SCC increased in relation to time only in the P-PRP group. A direct relation between time and treatment for IL-1, IL-2, and IL-6 was observed, while no differences were observed for IL-4. Furthermore, IL-1 and IL-2 increased in cows treated twice in both groups. IL-8, IFN-γ, and TNF-α showed a significant interaction between time and treatment. IFN-γ concentration was lower in the P-PRP group compared to the CS on days 0 and 22. Leukocyte counts were lower in P-PRP when compared to whole blood. TGF-ß1 and PF4 concentrations were higher in platelet lysates in comparison to P-PRGS and plasma. Moreover, PDGF-BB concentration was significantly higher in platelet lysates in comparison to plasma. Results obtained in this study demonstrate that SCM treated with PRP showed a lower rate of bacteriologic cure when compared to animals treated with CS.

Retrieval and treatment of patients with primary biliary cholangitis who are lost in the health system.

INTRODUCTION: hepatitis C patients loss to follow-up in the health care system has been shown to have negative consequences. This study aimed to investigate this issue as regards primary biliary cholangitis. METHODS: the databases (immunology, biochemistry, clinical reports, drug dispensation, appointments) of 4 reference hospitals in Spain (serving a population of 1,450,000 inhabitants) were analyzed. The diagnosis of primary biliary cholangitis was based on an antimitochondrial antibody titer ≥ 1:80, chronically elevated alkaline phosphatase, and the absence of other liver disease. Patients were classified as lost in the absence of reports indicating a diagnosis, specific medical follow-up, and/or treatment with bile salts. RESULTS: a total of 1372 patients with antimitochondrial antibody titers ≥ 1:80 were included between January 2010 and June 2019. A total of 697 (50.8 %) were classified as having primary biliary cholangitis, and 100 patients (14.3 %; 95 % CI: 11.8-17.2) were identified as lost. Of these, 30 were contacted and retrieved. The median age was 70 years, 93 % were female, median alkaline phosphatase was 185 IU/L, 10 % had pruritus, and 27 % had a transient elastography value > 9.5 kPa. The disease was confirmed and ursodeoxycholic acid was started in all 30 patients. Death was liver-related in 6 of the 100 patients classified as lost. CONCLUSION: up to 14.3 % of patients (1 out of 7) with a definitive diagnosis of primary biliary cholangitis remain undiagnosed, thus preventing monitoring and treatment. More than a quarter are at risk of advanced liver disease and its complications. Patients lost in the system must be identified and retrieved, and searching hospital databases is a suitable approach to meet this goal.

Application of udder surface temperature by infrared thermography for diagnosis of subclinical mastitis in Holstein cows located in tropical highlands.

Several reports have indicated that udder surface temperature (UST) can be a useful indicator of subclinical mastitis (SCM). The objective was to evaluate UST by infrared thermography (IRT) as a diagnostic tool for SCM and intramammary infection (IMI), and to assess the influence of environmental conditions in the potential diagnosis of this disease in dairy cows located at high-altitude tropical regions. A total of 105 cows (397 quarters) from 3 dairy farms with mechanical and manual milking methods were enrolled in the study. Subclinical mastitis was diagnosed when quarter samples had a somatic cell count (SCC) ≥200 × 103 cells/mL, microbial growth (MG) was defined when a major pathogen (≥1 cfu/plate) or Corynebacterium spp. (≥10 cfu/plate) was isolated, and IMI was defined as the presence of MG and SCC ≥100 × 103 cells/mL. Infrared images were taken with a thermal camera placed 1 m away from the udder, and shots of the rear and left and right lateral view were made during the morning milking, before any manipulation of the udder and employing dark cardboard on the contralateral side to avoid artifacts in the background. A multilevel mixed effects linear regression model clustered within cows and herd was performed to evaluate the associations with UST. Clinical performance was evaluated using the Youden index to establish the optimum UST thresholds, which were set at 32.6°C for any case definition when milking was by hand, at 33.7°C for MG, and at 34°C for SCM and IMI in machine-milked quarters. Sensitivity (Se), specificity (Sp), area under curve (AUC), and positive likelihood ratio (+LR) were also assessed. Test agreement was assessed by kappa coefficient (κ). The UST of healthy quarters ranged between (95% CI) 32.4 and 32.6°C, lower than SCM quarters (n = 88) at 32.9°C (95% CI: 32.7-33.1 °C), MG quarters (n = 56) at 33.5°C (95% CI: 33.3-33.7°C), and IMI quarters (n = 50) at 33.5°C (95% CI: 33.2-33.7 °C). The UST was also related to the milking method: higher temperatures were observed for hand milking (n = 90) compared with machine milking (n = 185). No relation between environmental conditions such as wind speed, atmospheric temperature, relative humidity, and temperature-humidity index and UST were observed during this study. For hand milking, the optimal UST threshold was 32.6°C; for SCM, Se = 0.53, Sp = 0.89, AUC = 0.71, κ = 0.4; for MG, Se = 0.83, Sp = 0.93, AUC = 0.88, κ = 0.77; and for IMI, Se = 0.82, Sp = 0.92, AUC = 0.87, κ = 0.74. The machine milking threshold for SCM resulted in Se = 0.42, Sp = 0.97, AUC = 0.70, κ = 0.47; for MG, Se = 0.82, Sp = 0.89, AUC = 0.85, κ = 0.60; and for IMI, Se = 0.82, Sp = 0.98, AUC = 0.90, κ = 0.79. These findings suggest that UST determined by IRT is higher in machine-milked cows and in quarters with MG and IMI than in healthy quarters; therefore, UST by IRT is a reliable, clinically useful method for MG and IMI diagnosis.

Optimization of azathioprine dose in combined treatment with anti-TNF-alpha in inflammatory bowel disease / Optimización de la dosis de azatioprina en tratamiento combinado con fármacos anti-TNF en la enfermedad inflamatoria intestinal

Introduction: The dose of thiopurine drugs in combined treatments with anti-TNF in inflammatory bowel disease (IBD) has not been clearly established. The purpose of this study is to assess whether the dose of azathioprine influences clinical and biochemical response/remission rates, and anti-TNF drug levels/antibody formation. Material and methods: Patients with IBD on combined maintenance treatment with azathioprine and infliximab or adalimumab were selected. Based on the dose of azathioprine, two groups were defined (standard: 2–2.5mg/kg/day; and decreased: less than 2mg/kg/day). Results: In the IFX group, there were no statistically significant differences (p=0.204) in the rates of remission (39% vs 41.3%), response (10% vs 21.7%) or failure (51.5% vs 37%) depending on the dose of thiopurine drugs. No differences were found between AZA-dose dependent IFX levels (2.46 vs 3.21μg/mL; p=0.211). In the adalimumab group, there were no statistically significant differences (p=0.83) in the rates of remission (66% vs 56%), response without remission (15.38% vs 25%) or failure (18% vs 18%) depending on the dose of thiopurines. With respect to ADA-levels, no differences were found in both groups (7.69 vs 8.23μg/mL; p=0.37). Conclusion: In our experience, no statistically significant differences were found in either anti-TNF levels or clinical-biological response/remission rates based on doses of azathioprine.(AU)

Introducción: La dosis adecuada de los fármacos tiopurínicos en tratamientos combinados con anti-TNF en la enfermedad inflamatoria intestinal (EII) no ha sido establecida con claridad. El propósito de este estudio es evaluar si la dosis de azatioprina influye en las tasas de respuesta/remisión clínica y bioquímica y en los niveles de fármaco anti-TNF/formación de anticuerpos. Material y métodos: Se seleccionaron pacientes con EII en tratamiento combinado de mantenimiento con azatioprina (AZA) e infliximab (IFX) o adalimumab (ADA). En función de la dosis de AZA, se definieron dos grupos (estándar: 2-2,5 mg/kg/día o disminuida: menos de 2 mg/kg/día). Resultados: En el grupo IFX no hubo diferencias estadísticamente significativas (p = 0,204) en las tasas de remisión (39 vs. 41,3%), respuesta (10 vs. 21,7%) o fracaso (51,5 vs. 37%), dependiendo de la dosis de fármacos tiopurínicos. No se encontraron diferencias entre los niveles de IFX dependientes de la dosis de AZA (2,46 vs. 3,21 μg/mL; p = 0,211). En el grupo de ADA no hubo diferencias estadísticamente significativas (p = 0,83) en las tasas de remisión (66 vs. 56%), respuesta sin remisión (15,38 vs. 25%) o fallo (18 vs. 18%), dependiendo de la dosis de tiopurinas. Con respecto a los niveles de ADA, no se encontraron diferencias en ambos grupos (7,69 vs. 8,23 μg/mL; p = 0,37). Conclusión: En nuestra experiencia, no se encontraron diferencias estadísticamente significativas ni en los niveles de anti-TNF ni en las tasas de respuesta/remisión clínico-biológica basadas en las dosis de azatioprina.(AU)

A Critical Overview of the Use of Platelet-Rich Plasma in Equine Medicine Over the Last Decade.

In the 1990s, the role of platelets in inflammation and tissue healing was finally recognized. Since then, the clinical use of platelet-derived products (hemocomponents), such as, platelet-rich plasma (PRP), markedly increased. The promise of a more economical option of a disease-modifying treatment led to the intensive and continuous research of PRP products and to its widespread clinical use. A number of protocols and commercial kits have been developed with the intention of creating a more practical and reliable option for clinical use in equine patients. Still, the direct comparison between studies is particularly challenging due to the lack of standardization on the preparation methods and product composition. The incomplete reports on PRP cellular concentration and the poorly designed in vivo studies are additional matters that contest the clinical efficiency of this biomaterial. To overcome such challenges, several in vitro and in vivo studies have been proposed. Specifically, experiments have greatly focused in protocol optimization and its effect in different tissues. Additionally, in vivo studies have proposed different biological products envisioning the upgrade of the anti-inflammatory cytokines trusting to increase its anti-inflammatory effect. The individual variability and health status of the animal, type of tissue and condition treated, and protocol implemented are known to influence on the product's cell and cytokine composition. Such variability is a main clinical concern once it can potentially influence on PRP's therapeutic effects. Thus, lack of qualitative and quantitative evidence-based data supporting PRP's clinical use persists, despite of the numerous studies intended to accomplish this purpose. This narrative review aims to critically evaluate the main research published in the past decade and how it can potentially impact the clinical use of PRP.

Optimization of azathioprine dose in combined treatment with anti-TNF-alpha in inflammatory bowel disease.

INTRODUCTION: The dose of thiopurine drugs in combined treatments with anti-TNF in inflammatory bowel disease (IBD) has not been clearly established. The purpose of this study is to assess whether the dose of azathioprine influences clinical and biochemical response/remission rates, and anti-TNF drug levels/antibody formation. MATERIAL AND METHODS: Patients with IBD on combined maintenance treatment with azathioprine and infliximab or adalimumab were selected. Based on the dose of azathioprine, two groups were defined (standard: 2-2.5mg/kg/day; and decreased: less than 2mg/kg/day). RESULTS: In the IFX group, there were no statistically significant differences (p=0.204) in the rates of remission (39% vs 41.3%), response (10% vs 21.7%) or failure (51.5% vs 37%) depending on the dose of thiopurine drugs. No differences were found between AZA-dose dependent IFX levels (2.46 vs 3.21µg/mL; p=0.211). In the adalimumab group, there were no statistically significant differences (p=0.83) in the rates of remission (66% vs 56%), response without remission (15.38% vs 25%) or failure (18% vs 18%) depending on the dose of thiopurines. With respect to ADA-levels, no differences were found in both groups (7.69 vs 8.23µg/mL; p=0.37). CONCLUSION: In our experience, no statistically significant differences were found in either anti-TNF levels or clinical-biological response/remission rates based on doses of azathioprine.

Importancia del uso adecuado del equipo de protección individual y la implementación de protocolos de seguridad perioperatorios durante la pandemia de COVID-19 / Importance of the Proper use of Personal Protective Equipment and the Implementation of Perioperative Safety Protocols During the COVID-19 Pandemic

RESUMEN El panorama que se presenta en la actualidad es un reto sin precedentes para el manejo de los pacientes quirúrgicos, la toma de decisiones y el empleo de recursos en cuanto a material y equipos de protección en el contexto de la pandemia por COVID-19. Por lo que el presente artículo pretende dar a conocer los lineamientos para el correcto actuar en el quirófano, el uso del equipo de protección individual, las indicaciones de cirugía y el mejor abordaje en el marco de esta situación. El principal objetivo de seguir estas recomendaciones es mitigar el riesgo de contagio y educar al personal de salud médico-quirúrgico para que esté preparado para hacer frente a esta pandemia.

ABSTRACT The current landscape represents an unprecedented challenge in managing surgical patients, decision-making and the use of resources such as protective equipment in the context of the COVID-19 pandemic. Therefore, the objective of this article is to provide guidelines for good conduct in the operating room, the use of personal protective equipment, suggestions for surgeries and the best approach in the context of this situation. The main objective of these recommendations is to mitigate the risk of contagion and to educate medical-surgical health personnel in how to deal with this pandemic.

Changes on the Structural Architecture and Growth Factor Release, and Degradation in Equine Platelet-Rich Fibrin Clots Cultured Over Time.

The aims of the present study were (1) to describe the microscopic and ultrastructural appearance of equine platelet-rich fibrin (PRF) clots and (2) to determine the release and degradation of transforming growth factor beta 1 (TGF-ß1) and insulin-like growth factor type I (IGF-I) from PRF clots incubated over 14 days. Whole blood from six horses was collected into plain tubes and centrifuged at 240 g for 8 minutes. Clots were evaluated by histology and by both transmission and scanning electronic microscopy (TEM and SEM). Growth factor concentrations were measured by ELISA at 48-hour intervals over 14 days and analyzed by one-way repeated-measures ANOVA. Histology showed a clot composed by a fibrin layer and a cellular layer with platelets and leukocytes. Scanning electron microscopy showed the cells trapped by an incipient fibrin network at 1 hour. At day 8, these cells were embedded by an incipient fibrin network. At day 14, the leukocytes and platelet aggregates from the clot were imbibed in an organized web of fibrin fibrils. TEM exhibited platelets with preserved cytoplasm and alpha granules randomly scattered at day 8, and damaged platelets with interrupted cytoplasm and organelle emigration to the periphery at day 14. TGF-ß1 and IGF-I concentrations showed a progressive increase until day 14. TGF-ß1 was released from PRF clots in a gradual and controlled manner, and increasing its concentration for two weeks, which supports TEM findings indicating that platelets began disintegrating by day 14. Furthermore, IGF-I production and release from PRF clots is sustained over time.

Síndrome de secreción inadecuada de hormona antidiurética postquimioembolización transarterial de un carcinoma hepatocelular / Syndrome of inappropriate antidiuretic hormone secretion following transarterial chemoembolisation of hepatocellular carcinoma

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Evaluation of the effect of experimentally induced cartilage defect and intra-articular hyaluronan on synovial fluid biomarkers in intercarpal joints of horses.

BACKGROUND: Inflammatory and degenerative activity inside the joint can be studied in vivo by analysis of synovial fluid biomarkers. In addition to pro-inflammatory mediators, several anabolic and anti-inflammatory substances are produced during the disease process. They counteract the catabolic effects of the pro-inflammatory cytokines and thus diminish the cartilage damage. The response of synovial fluid biomarkers after intra-articular hyaluronan injection, alone or in combination with other substances, has been examined only in a few equine studies. The effects of hyaluronan on some pro-inflammatory mediators, such as prostaglandin E2, have been documented but especially the effects on synovial fluid anti-inflammatory mediators are less studied. In animal models hyaluronan has been demonstrated to reduce pain via protecting nociceptive nerve endings and by blocking pain receptor channels. However, the results obtained for pain-relief of human osteoarthritis are contradictory. The aim of the study was to measure the synovial fluid IL-1ra, PDGF-BB, TGF-ß1 and TNF-α concentrations before and after surgically induced cartilage defect, and following intra-articular hyaluronan injection in horses. Eight Standardbred horses underwent bilateral arthroscopic surgeries of their intercarpal joints under general anaesthesia, and cartilage defect was created on the dorsal edge of the third carpal bone of one randomly selected intercarpal joint of each horse. Five days post-surgery, one randomly selected intercarpal joint was injected intra-articular with 3 mL HA (20 mg/mL). RESULTS: Operation type had no significant effect on the synovial fluid IL-1ra, PDGF-BB, TGF-ß1 and TNF-α concentrations but compared with baseline, synovial fluid IL-1ra and TNF-α concentrations increased. Intra-articular hyaluronan had no significant effect on the biomarker concentrations but a trend of mild improvement in the clinical signs of intra-articular inflammation was seen. CONCLUSIONS: Creation of the cartilage defect and sham-operation lead to an increase of synovial fluid IL-1ra and TNF-α concentrations but changes in concentrations of anabolic growth factors TGF-ß1 and PDGF-BB could not be documented 5 days after the arthroscopy. Intra-articular hyaluronan was well tolerated. Further research is needed to document possible treatment effects of intra-articular hyaluronan on the synovial fluid biomarkers of inflammation and cartilage metabolism.