Comparison of commercial enzyme-linked immunosorbent assays for diagnosis of contagious agalactia caused by Mycoplasma agalactiae

© 2022 A. Sánchez et al. This document is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted version of a Published Work that appeared in final form in Journal of Veterinary Research. To access the final edited and published work see https://doi.org/10.2478/jvetres-2022-0010Introduction: Contagious agalactia (CA) is a disease affecting small ruminants with worldwide distribution and caused by several mycoplasmas, especially M. agalactiae. The main option for systematic diagnosis under monitoring control programmes is the enzyme-linked immunosorbent assay (ELISA) test. Material and Methods: This study was designed to appraise the performance of two commercial indirect ELISA tests using M. agalactiae p48 protein and one using total protein, for antibody detection in small ruminants after natural infection with different M. agalactiae strains. We carried out the test evaluation using sera of confirmed M. agalactiae-positive goats with clinical signs. In addition, test agreement was assessed by kappa between the three commercial ELISA tests. Results: All three ELISA tests showed high validity scores (Youden’s J: 72.9–84%). The sensitivity values for the P48 protein-based tests were 76.9% and 84.6%, and was 79% for the total protein-based test. The specificity of all tests was 100%. In addition, between the total protein-based ELISA test and the other two ELISA tests based on the P48 protein, the agreement was substantial (kappa: 0.762–0.763) and the agreement between the latter two tests was almost perfect (kappa: 0.93). Conclusion: The validity parameters for all tests allowed their application for diagnostic purposes in lactating goats excreting M. agalactiae in milk and presenting clinical signs

Defectos del Tubo Neural y de Labio y Paladar Hendido: un Estudio Morfológico

El objetivo del trabajo fue realizar una evaluación morfológica externa de recién nacidos (RN) y lactantes con diagnóstico de defectos de tubo neural (DTN) y labio hendido c/s paladar hendido (LH c/s PH) para determinar el tipo de defecto, ubicación, extensión, clasificación y evaluar la proporción de RN con retardo del crecimiento intauterino (RCIU) y lactantes desnutridos. Estudio descriptivo. Se estudiaron 36 niños desde su nacimiento hasta los 12 meses de edad; 20 con DTN y 16 con LH c/s PH. El estudio se realizó en cinco hospitales de la ciudad de Chihuahua, México. Se hizo una evaluación morfológica externa y antropometría de los niños. Los DTN se clasificaron como lesiones abiertas y cerradas, como defectos altos o bajos, según el modelo de sitios múltiples y por la CIE-10. Los LH c/s PH se clasificaron como unilaterales o bilaterales, completos e incompletos y como aislados o múltiples. Se determinó RCIU en los RN y desnutrición en los lactantes. El análisis estadístico se realizó con el paquete STATA 8.0 para Windows. Se estudiaron 20 casos de DTN; 3 lactantes y 17 RN. De LH c/s PH fueron 8 lactantes y 8 RN. En cuanto a los DTN, 60% fueron mielomeningocele y correspondían a lesiones abiertas. El 85% se localizaron a nivel alto. En el modelo de cierres múltiples, el Z1 fue el 80%. Los LH c/s PH más frecuentes fueron aquellos con hendidura completa (50%). El 35% de los RN con DTN tuvieron RCIU y el 67% de los lactantes presentaron desnutrición. Es importante conocer los mecanismos del desarrollo de las anomalías congénitas ya que esto permite precisar el momento en que ocurrió la falla y permite estudiar los factores predisponentes, con lo cual se puede ofrecer asesoramiento genético para una posible prevención

Risk factors for thrombotic microangiopathy in allogeneic hematopoietic stem cell recipients receiving GVHD prophylaxis with tacrolimus plus MTX or sirolimus

Post-transplant complications.-- et al.Transplantation-associated thrombotic microangiopathy (TA-TMA) is a feared complication of allogeneic hematopoietic SCT (HSCT) owing to its high mortality rate. The use of calcineurin inhibitors or sirolimus (SIR) for GVHD prophylaxis has been suggested as a potential risk factor. However, the impact of tacrolimus (TAC) and SIR combinations on the increased risk of TA-TMA is currently not well defined. We retrospectively analyzed the incidence of TA-TMA in 102 allogeneic HSCT recipients who consecutively received TAC plus SIR (TAC/SIR) (n=68) or plus MTX (TAC/MTX)±ATG (n=34) for GVHD prophylaxis. No significant differences were observed in the incidence of TA-TMA between patients receiving TAC/SIR vs TAC/MTX±ATG (7.4% vs 8.8%, P=0.8). Only grade III-IV acute GVHD, previous HSCT and serum levels of TAC >25 ng/mL were associated with a greater risk of TA-TMA. Patients developing TA-TMA have significantly poorer survival (P<0.001); however, TA-TMA ceased to be an independent prognostic factor when it was included in a multivariate model. In conclusion, the combination of TAC/SIR does not appear to pose a higher risk of TA-TMA. By contrast, we identified three different risk groups for developing TA-TMA.Peer Reviewe

Outcomes of abdominal surgery in patients with liver cirrhosis

Patients suffering from liver cirrhosis (LC) frequently require non-hepatic abdominal surgery, even before liver transplantation. LC is an important risk factor itself for surgery, due to the higher than average associated morbidity and mortality. This high surgical risk occurs because of the pathophysiology of liver disease itself and to the presence of contributing factors, such as coagulopathy, poor nutritional status, adaptive immune dysfunction, cirrhotic cardiomyopathy, and renal and pulmonary dysfunction, which all lead to poor outcomes. Careful evaluation of these factors and the degree of liver disease can help to reduce the development of complications both during and after abdominal surgery. In the emergency setting, with the presence of decompensated LC, alcoholic hepatitis, severe/advanced LC, and significant extrahepatic organ dysfunction conservative management is preferred. A multidisciplinary, individualized, and specialized approach can improve outcomes; preoperative optimization after risk stratification and careful management are mandatory before surgery. Laparoscopic techniques can also improve outcomes. We review the impact of LC on surgical outcome in non-hepatic abdominal surgeries required in this cirrhotic population before, during, and after surgery

Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse

Multiple myeloma (MM) remains incurable despite the introduction of novel agents, and a relapsing course is observed in most patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less thoroughly investigated. In this study, an integrative analysis of DNA copy number, DNA methylation and gene expression was conducted in matched diagnosis and relapse samples from MM patients. Overall, the acquisition of abnormalities at relapse was much more frequent than the loss of lesions present at diagnosis, and DNA losses were significantly more frequent in relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly affect the gene expression of these samples, provoking a particular deregulation of the IL-8 pathway. On the other hand, no significant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although several statistical approaches were used to identify genes whose abnormal expression at relapse was regulated by methylation, only two genes that were significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative correlation between methylation and expression. Further analysis revealed that DNA methylation was involved in regulating SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were most likely not preceded by alterations in the corresponding DNA. Taken together, these results suggest that the genomic heterogeneity described at diagnosis remains at relapse.This work was partially supported by the Instituto de Salud Carlos III-Cofinanciación con fondos FEDER (PI080568, PS0901897 and PI13/00111), the Gerencia Regional de Salud, Junta de Castilla y León (GRS202/A08 and GRS 702/A/11), the Spanish Myeloma Network Program (RD06/0020/0006) and the Asociación Española Contra el Cáncer (AECC, GCB120981SAN).Peer Reviewe

The prognostic value of multiparameter flow cytometry minimal residual disease assessment in relapsed multiple myeloma

Letter to the editor.-- et al.This study was supported by the Cooperative Research Thematic Network grants RD12/0036/0058 of the Red de Cancer (Cancer Network of Excellence); Instituto de Salud Carlos III, Spain, Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS: PI060339; 06/1354; 02/0905; 01/0089/01-02; PS09/01897/01370; G03/136; Sara Borrell: CD13/00340); and Asociación Española Contra el Cáncer (GCB120981SAN), Spain. The study was also supported internationally by the International Myeloma Foundation Junior Grant Proposal and the Multiple Myeloma Research Foundation research fellow award.Peer Reviewe

Transcriptome analysis reveals molecular profiles associated with evolving steps of monoclonal gammopathies

This is an open-access paper.-- et al.A multistep model has been proposed of disease progression starting in monoclonal gammopathy of undetermined significance continuing through multiple myeloma, sometimes with an intermediate entity called smoldering myeloma, and ending in extramedullary disease. To gain further insights into the role of the transcriptome deregulation in the transition from a normal plasma cell to a clonal plasma cell, and from an indolent clonal plasma cell to a malignant plasma cell, we performed gene expression profiling in 20 patients with monoclonal gammopathy of undetermined significance, 33 with high-risk smoldering myeloma and 41 with multiple myeloma. The analysis showed that 126 genes were differentially expressed in monoclonal gammopathy of undetermined significance, smoldering myeloma and multiple myeloma as compared to normal plasma cell. Interestingly, 17 and 9 out of the 126 significant differentially expressed genes were small nucleolar RNA molecules and zinc finger proteins. Several proapoptotic genes (AKT1 and AKT2) were down-regulated and antiapoptotic genes (APAF1 and BCL2L1) were up-regulated in multiple myeloma, both symptomatic and asymptomatic, compared to monoclonal gammopathy of undetermined significance. When we looked for those genes progressively modulated through the evolving stages of monoclonal gammopathies, eight snoRNA showed a progressive increase while APAF1, VCAN and MEGF9 exhibited a progressive downregulation. In conclusion, our data show that although monoclonal gammopathy of undetermined significance, smoldering myeloma and multiple myeloma are not clearly distinguishable groups according to their gene expression profiling, several signaling pathways and genes were significantly deregulated at different steps of the transformation process.This study was partially supported by Spanish FIS (PI080568, PS09/01450 and PS0901897), “Gerencia Regional de Salud, Junta de Castilla y León” (GRS 702/A/11) grant, and the Spanish Myeloma Network Program (RD06/0020/0006, RD12/0036/0058 and RD12/0036/0046).Peer Reviewe

Analysis of incidence, risk factors and clinical outcome of thromboembolic and bleeding events in 431 allogeneic hematopoietic stem cell transplantation recipients

This is an open-access paper.-- et al.Allogeneic hematopoietic stem cell transplantation recipients have an increasing risk of both hemorrhagic and thrombotic complications. However, the competing risks of two of these life-threatening complications in these complex patients have still not been well defined. We retrospectively analyzed data from 431 allogeneic transplantation recipients to identify the incidence, risk factors and mortality due to thrombosis and bleeding. Significant clinical bleeding was more frequent than symptomatic thrombosis. The cumulative incidence of a bleeding episode was 30.2% at 14 years. The cumulative incidence of a venous or arterial thrombosis at 14 years was 11.8% and 4.1%, respectively. The analysis of competing factors for venous thrombosis revealed extensive chronic graft-versus-host disease to be the only independent prognostic risk factor. By contrast, six factors were associated with an increased risk of bleeding; advanced disease, ablative conditioning regimen, umbilical cord blood transplantation, anticoagulation, acute III-IV graft-versus-host disease, and transplant-associated microangiopathy. The development of thrombosis did not significantly affect overall survival (P=0.856). However, significant clinical bleeding was associated with inferior survival (P<0.001). In allogeneic hematopoietic stem cell transplantation, significant clinical bleeding is more common than thrombotic complications and affects survival.Peer Reviewe

Precision of ultrasound-guided versus anatomical palpation-guided needle placement of the ulnar nerve at the cubital tunnel: a cadaveric study

Percutaneous electrical stimulation has been performed for years with only the assistance of anatomical landmarks. The development of real-time ultrasonography guidance has improved the precision and safety of these percutaneous interventions. Despite ultrasound-guided and palpation-guided procedures being performed routinely for targeting nerve tissues in the upper extremity, the precision and safety of these techniques are unknown. The aim of this cadaveric study was to determine and compare the precision and safety of ultrasound-guided versus palpation-guided needling procedure with and without the handpiece of the ulnar nerve on a cadaveric model. Five physical therapists performed a series of 20 needle insertion tasks each (n = 100), 10 palpation-guided (n = 50) and 10 ultrasound-guided (n = 50) on cryopreserved specimens. The purpose of the procedure was to place the needle in proximity to the ulnar nerve at the cubital tunnel. The distance to target, time performance, accurate rate, number of passes, and unintentional puncture of surrounding structures were compared. The ultrasound-guided procedure was associated with higher accuracy (66% vs. 96%), lower distance from needle to the target (0.48 ± 1.37 vs. 2.01 ± 2.41 mm), and a lower frequency of perineurium puncture (0% vs. 20%) when compared with the palpation-guided procedure. However, the ultrasound-guided procedure required more time (38.33 ± 23.19 vs. 24.57 ± 17.84 s) than the palpation-guided procedure (all, p &lt; 0.001). Our results support the assumption that ultrasound guidance improves the accuracy of needling procedures on the ulnar nerve at the cubital tunnel when compared with palpation guidance

Lenalidomide-dexamethasone versus observation in high-risk smoldering myeloma after 12 years of median follow-up time: A randomized, open-label study

[Background]: Smoldering multiple myeloma (SMM) is a heterogeneous disease in terms of progression to myeloma (MM), but its standard of care continues to be observation. [Methods]: The QuiRedex phase 3 trial initiated in 2007 included 119 high-risk patients with SMM randomized to treatment or observation. Treatment consisted of nine 4-week induction cycles (lenalidomide [Rd], 25 mg on days 1–21 plus dexamethasone, 20 mg on days 1–4 and 12–15), followed by maintenance (R, 10 mg on days 1–21) for up to 2 years. The primary end-point was time to progression (TTP) to myeloma based on per protocol population. Secondary end-points were overall survival (OS), response rate, and safety. An update of the trial after a long-term follow-up is presented here. This trial was registered with ClinicalTrials.gov (NCT00480363). [Findings]: After a median follow-up time of 12.5 years (range: 10.4–13.6), the median TTP to MM was 2.1 years in the observation arm and 9.5 years in the Rd arm (HR: 0.28, 95% CI: 0.18–0.44, p < 0.0001). The median OS was 8.5 years in the abstention arm and not reached in the Rd group (HR: 0.57, 95% CI: 0.34–0.95, p = 0.032). Patients who progressed received optimized treatments according to the standards of care, and the OS from progression was comparable in both arms (p = 0.96). [Interpretation]: This analysis confirms that early treatment with Rd for high-risk SMM translates into a sustained benefit in both TTP and OS.This study was also supported by the Cooperative Research Thematic Network grant RD12/0036/0058 and RD12/0036/0046 and Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria, Spain. (FIS:PI12/02311/01761/01569)