Stage Migration in Canine Multicentric Lymphoma: Impact of Diagnostic Techniques on Assessing Disease Extent.

BACKGROUND/AIM: Stage migration, a phenomenon triggered by technological advancements allowing more sensitive tumor spread detection, results in alterations in the distribution of cancer stages within a population. Canine multicentric lymphoma is staged I to V based on the affected anatomic site(s) and substage a or b depending on the presence of tumor-related clinical signs. The primary objective of this study was to assess the influence of various diagnostic techniques on staging accuracy and determine whether multiple staging methods lead to significant stage migration, impacting the reliability of disease stage assignments. MATERIALS AND METHODS: Dogs cytologically diagnosed with multicentric lymphoma were staged using four different staging methods (A-D): A (physical examination, hemogram, blood smear), B (A plus thoracic X-ray, abdominal ultrasound), C (B plus liver and spleen cytology) and D (C plus bone marrow cytology). RESULTS: Twenty-three dogs were enrolled: 16 females (70%) and seven males (30%). Regarding immunophenotype, 21 dogs (91.3%) were B-cell and two dogs (8.7%) were T-cell. Stage migration was observed between all staging methods. Between A and B, 12 animals migrated from stage III to stage IV. Between B and C, four animals migrated, three to a higher stage (stage III to IV) and one to a lower stage (stage IV to III). Between C and D, one animal migrated from stage IV to V. The differences between staging methods A and B were statistically significant (p≤0.001). CONCLUSION: Stage migration in canine multicentric lymphoma depends on the diagnostic methods used and reinforces the need to use standardized staging methods to avoid it.

Human gut microbiome, diet, and mental disorders.

Diet is one of the most important external factor shaping the composition and metabolic activities of the gut microbiome. The gut microbiome plays a crucial role in host health, including immune system development, nutrients metabolism, and the synthesis of bioactive molecules. In addition, the gut microbiome has been described as critical for the development of several mental disorders. Nutritional psychiatry is an emerging field of research that may provide a link between diet, microbial function, and brain health. In this study, we have reviewed the influence of different diet types, such as Western, Mediterranean, vegetarian, and ketogenic, on the gut microbiota composition and function, and their implication in various neuropsychiatric and psychological disorders.

Melanoma of the dog and cat: consensus and guidelines.

Melanoma of the dog and cat poses a clinical challenge to veterinary practitioners across the globe. As knowledge evolves, so too do clinical practices. However, there remain uncertainties and controversies. There is value for the veterinary community at large in the generation of a contemporary wide-ranging guideline document. The aim of this project was therefore to assimilate the available published knowledge into a single accessible referenced resource and to provide expert clinical guidance to support professional colleagues as they navigate current melanoma challenges and controversies. Melanocytic tumors are common in dogs but rare in cats. The history and clinical signs relate to the anatomic site of the melanoma. Oral and subungual malignant melanomas are the most common malignant types in dogs. While many melanocytic tumors are heavily pigmented, making diagnosis relatively straightforward, melanin pigmentation is variable. A validated clinical stage scheme has been defined for canine oral melanoma. For all other locations and for feline melanoma, TNM-based staging applies. Certain histological characteristics have been shown to bear prognostic significance and can thus prove instructive in clinical decision making. Surgical resection using wide margins is currently the mainstay of therapy for the local control of melanomas, regardless of primary location. Radiotherapy forms an integral part of the management of canine oral melanomas, both as a primary and an adjuvant therapy. Adjuvant immunotherapy or chemotherapy is offered to patients at high risk of developing distant metastasis. Location is the major prognostic factor, although it is not completely predictive of local invasiveness and metastatic potential. There are no specific guidelines regarding referral considerations for dogs with melanoma, as this is likely based on a multitude of factors. The ultimate goal is to provide the best options for patients to extend quality of life and survival, either within the primary care or referral hospital setting.

OPTImized coronary interventions eXplaIn the bEst cliNical outcomEs (OPTI-XIENCE) study. Rationale and study design.

INTRODUCTION: Clinical events may occur after percutaneous coronary intervention (PCI), particularly in complex lesions and complex patients. The optimization of PCI result, using pressure guidewire and intracoronary imaging techniques, may reduce the risk of these events. The hypothesis of the present study is that the clinical outcome of patients with indication of PCI and coronary stent implantation that are at high risk of events can be improved with an unrestricted use of intracoronary tools that allow PCI optimization. METHODS AND ANALYSIS: Observational prospective multicenter international study, with a follow-up of 12 months, including 1064 patients treated with a cobalt­chromium everolimus-eluting stent. Inclusion criteria include any of the following: Lesion length > 28 mm; Reference vessel diameter < 2.5 mm or > 4.25 mm; Chronic total occlusion; Bifurcation with side branch ≥2.0 mm;Ostial lesion; Left main lesion; In-stent restenosis; >2 lesions stented in the same vessel; Treatment of >2 vessels; Acute myocardial infarction; Renal insufficiency; Left ventricular ejection fraction <30 %; Staged procedure. The control group will be comprised by a similar number of matched patients included in the "extended risk" cohort of the XIENCE V USA study. The primary endpoint will be the 1-year rate of target lesion failure (TLF) (composite of ischemia-driven TLR, myocardial infarction (MI) related to the target vessel, or cardiac death related to the target vessel). Secondary endpoints will include overall mortality, cardiovascular mortality, acute myocardial infarction, TVR, TLR, target vessel failure, and definitive or probable stent thrombosis at 1 year. IMPLICATIONS: The ongoing OPTI-XIENCE study will contribute to the growing evidence supporting the use of intra-coronary imaging techniques for stent optimization in patients with complex coronary lesions.

The plasma metabolome of long COVID patients two years after infection.

One of the major challenges currently faced by global health systems is the prolonged COVID-19 syndrome (also known as "long COVID") which has emerged as a consequence of the SARS-CoV-2 epidemic. It is estimated that at least 30% of patients who have had COVID-19 will develop long COVID. In this study, our goal was to assess the plasma metabolome in a total of 100 samples collected from healthy controls, COVID-19 patients, and long COVID patients recruited in Mexico between 2020 and 2022. A targeted metabolomics approach using a combination of LC-MS/MS and FIA MS/MS was performed to quantify 108 metabolites. IL-17 and leptin were measured in long COVID patients by immunoenzymatic assay. The comparison of paired COVID-19/long COVID-19 samples revealed 53 metabolites that were statistically different. Compared to controls, 27 metabolites remained dysregulated even after two years. Post-COVID-19 patients displayed a heterogeneous metabolic profile. Lactic acid, lactate/pyruvate ratio, ornithine/citrulline ratio, and arginine were identified as the most relevant metabolites for distinguishing patients with more complicated long COVID evolution. Additionally, IL-17 levels were significantly increased in these patients. Mitochondrial dysfunction, redox state imbalance, impaired energy metabolism, and chronic immune dysregulation are likely to be the main hallmarks of long COVID even two years after acute COVID-19 infection.

Immune response of DNA vaccinated-gilthead seabream (Sparus aurata) against LCDV-Sa infection: relevance of the inflammatory process.

Lymphocystis disease is one of the main viral pathologies affecting cultured gilthead seabream (Sparus aurata) in the Mediterranean region. Recently, we have developed a DNA vaccine based on the major capsid protein (MCP) of the Lymphocystis disease virus 3 (LCDV-Sa). The immune response triggered by either LCDV-Sa infection or vaccination have been previously studied and seem to be highly related to the modulation of the inflammatory and the IFN response. However, a comprehensive evaluation of immune-related gene expression in vaccinated fish after viral infection to identify immunogenes involved in vaccine-induced protection have not been carried out to date. The present study aimed to fulfill this objective by analyzing samples of head-kidney, spleen, intestine, and caudal fin from fish using an OpenArray® platform containing targets related to the immune response of gilthead seabream. The results obtained showed an increase of deregulated genes in the hematopoietic organs between vaccinated and non-vaccinated fish. However, in the intestine and fin, the results showed the opposite trend. The global effect of fish vaccination was a significant decrease (p<0.05) of viral replication in groups of fish previously vaccinated, and the expression of the following immune genes related to viral recognition (tlr9), humoral and cellular response (rag1 and cd48), inflammation (csf1r, elam, il1ß, and il6), antiviral response (isg15, mx1, mx2, mx3), cell-mediated cytotoxicity (nccrp1), and apoptosis (prf1). The exclusive modulation of the immune response provoked by the vaccination seems to control the progression of the infection in the experimentally challenged gilthead seabream.

Seguridad y viabilidad del acceso radial para intervenciones coronarias percutáneas de oclusiones totales crónicas / Safety and feasibility of transradial access for percutaneous coronary intervention in chronic total occlusions

Introducción y objetivos El acceso femoral es la vía vascular mayoritariamente utilizada en intervenciones coronarias percutáneas de desobstrucción de oclusiones totales crónicas (ICP-OTC). El objetivo de este estudio fue evaluar la viabilidad y seguridad del acceso radial en un programa de ICP-OTC y su impacto sobre el resultado clínico y angiográfico y la duración de la estancia hospitalaria. Métodos Estudio multicéntrico retrospectivo de cohortes en el que se incluyeron de forma consecutiva 2.550 procedimientos de ICP-OTC con información precisa sobre acceso vascular. Un total de 896 casos se realizaron por acceso radial puro y 1.654 se realizaron con al menos una punción femoral. Se analizaron datos clínicos y angiográficos. Resultados La edad media fue de 66,3±11,4 años. La puntuación Japan-chronic total occlusion (J-CTO) fue similar en ambos grupos (2,7±0,3). El éxito del procedimiento se obtuvo en un 79,6% de los procedimientos, 78,2% y 82,1% en la cohorte transfemoral y transradial respectivamente p=0,02). Las complicaciones intrahospitalarias periprocedimiento se observaron en el 5,1% y el 2,3% (p=0,02), con un menor número de complicaciones vasculares dependientes del sitio de punción (2,3% frente a 0,2%, p=0,009). La duración media del ingreso hospitalario fue significativamente menor en el grupo radial (0,89±1,4 frente a 2,2±3,2 días; p<0,001). Conclusiones Un programa de acceso radial para la ICP-OTC es seguro y efectivo para la mayoría de las oclusiones. La estrategia transradial permite un menor número de complicaciones vasculares y una estancia media más corta sin comprometer la tasa de éxito del procedimiento (AU)

Introduction and objectives Transfemoral access is the most frequently used vascular approach in chronic total occlusion percutaneous coronary interventions (CTO-PCI). The aim of this study was to evaluate the safety and feasibility of a transradial access CTO-PCI program and its impact on angiographic and clinical results and length of hospital stay. Methods Retrospective multicenter cohort study including 2550 consecutive CTO-PCI procedures included in a multicenter registry with accurate information on vascular access. A total of 896 procedures were performed as radial-only access while 1654 were performed through at least 1 femoral puncture. Clinical and angiographic data were collected. Results The mean age was 66.3± 11.4 years. The mean Japan-chronic total occlusion score (2.7±0.3) was similar in the 2 groups. Successful revascularization was achieved in 2009 (79.6%) cases, 78.2% and 82.1% in the femoral and radial access cohorts, respectively (P=.002). Periprocedural in-hospital complications were observed in 5.1% and 2.3% (P=.02), with fewer access site-dependant vascular complications in the transradial cohort (2.3% vs 0.2%; P=.009). The mean length of hospital stay was significantly shorter in the transradial access group (0.89±1.4 vs 2.2±3.2 days, P<.001). Conclusions A transradial program for CTO-PCI is safe and effective in most CTO lesions. The transradial strategy has fewer vascular complications and shorter length of hospital stay without compromising the success rate (AU)

Untargeted analysis in post-COVID-19 patients reveals dysregulated lipid pathways two years after recovery.

Introduction: Similar to what it has been reported with preceding viral epidemics (such as MERS, SARS, or influenza), SARS-CoV-2 infection is also affecting the human immunometabolism with long-term consequences. Even with underreporting, an accumulated of almost 650 million people have been infected and 620 million recovered since the start of the pandemic; therefore, the impact of these long-term consequences in the world population could be significant. Recently, the World Health Organization recognized the post-COVID syndrome as a new entity, and guidelines are being established to manage and treat this new condition. However, there is still uncertainty about the molecular mechanisms behind the large number of symptoms reported worldwide. Aims and Methods: In this study we aimed to evaluate the clinical and lipidomic profiles (using non-targeted lipidomics) of recovered patients who had a mild and severe COVID-19 infection (acute phase, first epidemic wave); the assessment was made two years after the initial infection. Results: Fatigue (59%) and musculoskeletal (50%) symptoms as the most relevant and persistent. Functional analyses revealed that sterols, bile acids, isoprenoids, and fatty esters were the predicted metabolic pathways affected in both COVID-19 and post-COVID-19 patients. Principal Component Analysis showed differences between study groups. Several species of phosphatidylcholines and sphingomyelins were identified and expressed in higher levels in post-COVID-19 patients compared to controls. The paired analysis (comparing patients with an active infection and 2 years after recovery) show 170 dysregulated features. The relationship of such metabolic dysregulations with the clinical symptoms, point to the importance of developing diagnostic and therapeuthic markers based on cell signaling pathways.

Tonsillar carcinoma in dogs: Treatment outcome and potential prognostic factors in 123 cases.

BACKGROUND: Tonsillar carcinomas are rarely reported in dogs. Information on outcome after treatment is sparse and prognosis is guarded to poor. HYPOTHESIS/OBJECTIVES: Assess treatment outcome and potential prognostic factors in a population of dogs with cytological or histopathological diagnosis of tonsillar carcinoma. ANIMALS: A total of 123 client-owned dogs with diagnosis of tonsillar carcinoma confirmed by cytology or histopathology. METHODS: Retrospective, multi-institutional study. Medical records of 12 institutions were reviewed from 2012 to 2021. RESULTS: Treatment included surgery, chemotherapy (conventional, tyrosine kinase inhibitors or metronomic chemotherapy), radiotherapy, nonsteroidal anti-inflammatory drugs (NSAIDs) or a combination of these. Surgery was performed in 68 cases, chemotherapy was administered in association with NSAIDs in 64 cases, NSAIDs were used alone in 14 cases and in association with surgery in 21 cases, whereas radiotherapy was used alone or in combination with surgery or chemotherapy in 20 cases. Overall survival time (OST) was 126 days (95% confidence interval [CI], 88-164). Significantly longer survival (P < .001) was seen in dogs without evidence of metastatic disease (median survival time, 381 days; 95% CI, 116-646). Other significant positive prognostic factors included absence of clinicals signs at presentation, surgery (tonsillectomy), use of adjuvant chemotherapy and use of NSAIDs. CONCLUSION AND CLINICAL IMPORTANCE: Asymptomatic dogs, those treated with surgery, those that received adjuvant chemotherapy, and those that received NSAIDs may have a better prognosis than previously expected, but overall survival remains short for dogs with tonsillar carcinoma.

Clinical presentation, treatment and outcome in 23 cats with laryngeal or tracheal lymphoma.

OBJECTIVES: Feline primary laryngeal or tracheal lymphoma (PLTL) is an uncommon extranodal presentation. Information on long-term survival is scarce, although some small case series describe this being achieved with multiagent protocols; an accurate outcome for cats with PLTL is yet to be determined. The aim of this study was to gather information on the clinical presentation, response to treatment and outcome in a large case series of feline PLTL. METHODS: This retrospective multicentre study included cats with a cytological or histopathological confirmation of PLTL. Histopathology samples, when available, were reassessed for grade and immunophenotype. Clinical (age, signalment, retroviral status, presence of anaemia, clinical signs, location and therapy type) and outcome (response, progression-free survival [PFS] and overall survival [OS]) variables were recorded. Survival analyses to assess the impact of variables on PFS and OS were performed. RESULTS: Twenty-three cases were included; cats had a median age of 11 years (range 2-16) and the male:female ratio was 3.6:1. Common clinical signs at presentation included increased respiratory effort (74%) and abnormal upper respiratory tract sounds (48%). Immunophenotyping was performed in 48% of cases and all were B cell. Debulking surgery was performed in 26% of cases. All cats received chemotherapy, COP (cyclophosphamide, vincristine and prednisolone; 39%), CHOP (cyclophosphamide, vincristine, doxorubicin and prednisolone; 44%) and other protocols (17%); 35% had a partial response and 65% a complete response. Median PFS and OS were 909 days (range 23-1484) and 909 days (range 23-2423), respectively. Complete response was associated with longer PFS (P <0.001) and OS (P = 0.012). Pretreatment with steroids was associated with longer OS (P = 0.003). No other variable was found to be significant. CONCLUSIONS AND RELEVANCE: PLTL in cats is mostly of a B-cell phenotype, could be of a low-to-medium grade, and may respond to surgical and medical treatment with a longer survival time than has previously been reported.

Overlapping versus single long stents in long chronic total occlusions: insights of the Iberian CTO Registry.

BACKGROUND: It is unknown whether the availability of long drug-eluting stents modify the PCI strategy of long CTO. To describe the contemporary PCI strategy of long chronic total occlusions (CTO) using overlapping (OS) or single long stents (SS) and to analyze its results. METHODS: 2842 consecutive CTO PCIs were included. Those with an occlusion length ≥20 mm in which ≥1 drug eluting stent (DES) was implanted were analyzed. We compared procedural characteristics and clinical outcomes of CTO treated with OS or SS. RESULTS: 1088 CTO PCIs were analyzed (79.9% males; 64.7±10.6 years). Mean J-score was 2.8±0.9. A SS was used in 38.5% of cases and OS in 61.5%. Total stent length was 64.1±29.9 mm; it was higher in the OS group (OS: 79.9±25.5 mm vs. SS: 38.3±14.7 mm; P<0.0001). Mean number of stents in the OS group was 2.3±1. Very long stents (≥40 mm) were used in 27.4% of cases, more frequently in the OS group (OS:32.4% vs. SS:19.3%; P<0.0001). After a mean follow-up of 19±15.9 months, the rate of adverse events (MACE) was 2% (cardiac death: 1.6%, myocardial infarction: 1.6%, target lesion revascularization: 1.9% and stent thrombosis: 0.18%) with no significant differences between both groups. Overlapping was not an independent predictor of MACE. CONCLUSIONS: In long CTO PCIs, OS is more frequently used than single stenting, especially in more complex procedures. Clinical outcomes at a mid-term follow-up are favorable. Using newer generation DES, overlapping was not an independent predictor of MACE; however, a trend toward a higher event rate was observed in the OS group.

Safety and feasibility of transradial access for percutaneous coronary intervention in chronic total occlusions.

INTRODUCTION AND OBJECTIVES: Transfemoral access is the most frequently used vascular approach in chronic total occlusion percutaneous coronary interventions (CTO-PCI). The aim of this study was to evaluate the safety and feasibility of a transradial access CTO-PCI program and its impact on angiographic and clinical results and length of hospital stay. METHODS: Retrospective multicenter cohort study including 2550 consecutive CTO-PCI procedures included in a multicenter registry with accurate information on vascular access. A total of 896 procedures were performed as radial-only access while 1654 were performed through at least 1 femoral puncture. Clinical and angiographic data were collected. RESULTS: The mean age was 66.3± 11.4 years. The mean Japan-chronic total occlusion score (2.7±0.3) was similar in the 2 groups. Successful revascularization was achieved in 2009 (79.6%) cases, 78.2% and 82.1% in the femoral and radial access cohorts, respectively (P=.002). Periprocedural in-hospital complications were observed in 5.1% and 2.3% (P=.02), with fewer access site-dependant vascular complications in the transradial cohort (2.3% vs 0.2%; P=.009). The mean length of hospital stay was significantly shorter in the transradial access group (0.89±1.4 vs 2.2±3.2 days, P<.001). CONCLUSIONS: A transradial program for CTO-PCI is safe and effective in most CTO lesions. The transradial strategy has fewer vascular complications and shorter length of hospital stay without compromising the success rate.

Long-Term Vascular Function in CTO Recanalization: A Randomized Clinical Trial of Ticagrelor vs. Clopidogrel.

BACKGROUND: Coronary vascular function of a chronic coronary total occlusion (CTO) immediately after recanalization is known to be poor and to be partially improved by pre-treatment with loading dose of ticagrelor vs. clopidogrel. It is unknown if this vascular dysfunction is maintained at long-term follow-up and may be improved by 1-year dual antiplatelet therapy (DAPT). METHODS: The TIGER is a prospective, open-label, two parallel-group controlled clinical trial, which 1:1 randomized 50 CTO patients to pre-PCI loading dose and subsequent 1-year DAPT with ticagrelor vs. clopidogrel. Coronary blood flow (CBF) under stepwise adenosine infusion was assessed after drug loading dose and at follow-up and compared between the two drug groups, adjusting for time of follow-up. RESULTS: Out of 50 patients with index CBF evaluation, 38 (76%) patients underwent angiographic follow-up (23 and 15 at 1 and 3-year, respectively) and Doppler data was available in 35 (70%). A high CBF area under the curve (AUC), already observed after loading dose in ticagrelor vs. clopidogrel group (p = 0.027), was maintained at follow-up (AUC 34815.22 ± 24,206.06 vs. AUC 22712.47 ± 13,768.95; p = 0.071). Specifically, whereas high ticagrelor loading dose-related CBF was sustained at follow-up (p = 0.933), clopidogrel loading dose-related CBF increased at follow-up (p = 0.039). CONCLUSION: The TIGER trial showed that DAPT with ticagrelor maintained a non-significantly higher CBF in a recanalized CTO as compared to clopidogrel, whose treated patients exhibit a lower CBF immediately after PCI with a significant increase at follow-up. The clinical value of such sustained high coronary flow should be evaluated in a larger group of patients. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02211066 (ClinicalTrials.gov number NCT02211066).

Plaque modification in calcified chronic total occlusions: the PLACCTON study.

INTRODUCTION AND OBJECTIVES: Severe calcification is present in> 50% of coronary chronic total occlusions (CTOs) undergoing percutaneous intervention. We aimed to describe the contemporary use and outcomes of plaque modification devices (PMDs) in this context. METHODS: Patients were included in the prospective, consecutive Iberian CTO registry (32 centers in Spain and Portugal), from 2015 to 2020. Comparison was performed according to the use of PMDs. RESULTS: Among 2235 patients, wire crossing was achieved in 1900 patients and PMDs were used in 134 patients (7%), requiring more than 1 PMD in 24 patients (1%). The selected PMDs were rotational atherectomy (35.1%), lithotripsy (5.2%), laser (11.2%), cutting/scoring balloons (27.6%), OPN balloons (2.9%), or a combination of PMDs (18%). PMDs were used in older patients, with greater cardiovascular burden, and higher Syntax and J-CTO scores. This greater complexity was associated with longer procedural time but similar total stent length (52 vs 57mm; P=.105). If the wire crossed, the procedural success rate was 87.2% but increased to 96.3% when PMDs were used (P=.001). Conversely, PMDs were not associated with a higher rate of procedural complications (3.7 vs 3.2%; P=.615). Despite the worse baseline profile, at 2 years of follow-up there were no differences in the survival rate (PMDs: 94.3% vs no-PMDs: 94.3%, respectively; P=.967). CONCLUSIONS: Following successful wire crossing in CTOs, PMDs were used in 7% of the lesions with an increased success rate. Mid-term outcomes were comparable despite their worse baseline profile, suggesting that broader use of PMDs in this setting might have potential technical and prognostic benefits.

Kynurenine and Hemoglobin as Sex-Specific Variables in COVID-19 Patients: A Machine Learning and Genetic Algorithms Approach.

Differences in clinical manifestations, immune response, metabolic alterations, and outcomes (including disease severity and mortality) between men and women with COVID-19 have been reported since the pandemic outbreak, making it necessary to implement sex-specific biomarkers for disease diagnosis and treatment. This study aimed to identify sex-associated differences in COVID-19 patients by means of a genetic algorithm (GALGO) and machine learning, employing support vector machine (SVM) and logistic regression (LR) for the data analysis. Both algorithms identified kynurenine and hemoglobin as the most important variables to distinguish between men and women with COVID-19. LR and SVM identified C10:1, cough, and lysoPC a 14:0 to discriminate between men with COVID-19 from men without, with LR being the best model. In the case of women with COVID-19 vs. women without, SVM had a higher performance, and both models identified a higher number of variables, including 10:2, lysoPC a C26:0, lysoPC a C28:0, alpha-ketoglutaric acid, lactic acid, cough, fever, anosmia, and dysgeusia. Our results demonstrate that differences in sexes have implications in the diagnosis and outcome of the disease. Further, genetic and machine learning algorithms are useful tools to predict sex-associated differences in COVID-19.