Deregulated immune cell recruitment orchestrated by c-MET impairs pulmonary inflammation and fibrosis.

BACKGROUND: Pulmonary fibrosis (PF) represents the pathologic end stage of several interstitial lung diseases (ILDs) associated with high morbidity and mortality rates. However, current treatments can only delay disease progression rather than provide a cure. The role of inflammation in PF progression is well-established, but new insights into immune regulation are fundamental for developing more efficient therapies. c-MET signaling has been implicated in the migratory capacity and effector functions of immune cells. Nevertheless, the role of this signaling pathway in the context of PF-associated lung diseases remains unexplored. METHODS: To determine the influence of c-MET in immune cells in the progression of pulmonary fibrosis, we used a conditional deletion of c-Met in immune cells. To induce pulmonary fibrosis mice were administered with bleomycin (BLM) intratracheally. Over the course of 21 days, mice were assessed for weight change, and after euthanasia at different timepoints, bronchoalveolar lavage fluid cells and lung tissue were assessed for inflammation and fibrosis. Furthermore, c-MET expression was assessed in cryobiopsy sections, bronchoalveolar lavage fluid cells samples and single cell RNA-sequencing dataset from human patients with distinct interstitial lung diseases. RESULTS: c-MET expression was induced in lung immune cells, specifically in T cells, interstitial macrophages, and neutrophils, during the inflammatory phase of BLM-induced PF mouse model. Deletion of c-Met in immune cells correlated with earlier weight recovery and improved survival of BLM-treated mice. Moreover, the deletion of c-Met in immune cells was associated with early recruitment of the immune cell populations, normally found to express c-MET, leading to a subsequent attenuation of the cytotoxic and proinflammatory environment. Consequently, the less extensive inflammatory response, possibly coupled with tissue repair, culminated in less exacerbated fibrotic lesions. Furthermore, c-MET expression was up-regulated in lung T cells from patients with fibrosing ILD, suggesting a potential involvement of c-MET in the development of fibrosing disease. CONCLUSIONS: These results highlight the critical contribution of c-MET signaling in immune cells to their enhanced uncontrolled recruitment and activation toward a proinflammatory and profibrotic phenotype, leading to the exacerbation of lung injury and consequent development of fibrosis.

Electrochemotherapy in dogs and cats-A review.

Electrochemotherapy (ECT) is a treatment modality that combines the electroporation of cell membranes with chemotherapy to facilitate the transport of non-permeant molecules into cells. Several canine and feline studies have shown promising results, suggesting that ECT can be a valid adjuvant or alternative treatment option for some tumours. The objective of this paper is to provide a bibliographic review of the principles and applications of ECT in veterinary medicine and to compare to its use in human medicine.

Dual T cell receptor/chimeric antigen receptor engineered NK-92 cells targeting the HPV16 E6 oncoprotein and the tumor-associated antigen L1CAM exhibit enhanced cytotoxicity and specificity against tumor cells.

The human papillomavirus type 16 (HPV16) causes a large fraction of genital and oropharyngeal carcinomas. To maintain the transformed state, the tumor cells must continuously synthesize the E6 and E7 viral oncoproteins, which makes them tumor-specific antigens. Indeed, specific T cell responses against them have been well documented and CD8+ T cells engineered to express T cell receptors (TCRs) that recognize epitopes of E6 or E7 have been tested in clinical studies with promising results, yet with limited clinical success. Using CD8+ T cells from peripheral blood of healthy donors, we have identified two novel TCRs reactive to an unexplored E618-26 epitope. These TCRs showed limited standalone cytotoxicity against E618-26-HLA-A*02:01-presenting tumor cells. However, a single-signaling domain chimeric antigen receptor (ssdCAR) targeting L1CAM, a cell adhesion protein frequently overexpressed in HPV16-induced cancer, prompted a synergistic effect that significantly enhanced the cytotoxic capacity of NK-92/CD3/CD8 cells armored with both TCR and ssdCAR when both receptors simultaneously engaged their respective targets, as shown by live microscopy of 2-D and 3-D co-cultures. Thus, virus-specific TCRs from the CD8+ T cell repertoire of healthy donors can be combined with a suitable ssdCAR to enhance the cytotoxic capacity of the effector cells and, indirectly, their specificity.

Role of Presurgical Gut Microbial Diversity in Roux-en-Y Gastric Bypass Weight-Loss Response: A Cohort Study.

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) substantially alters the gut microbial composition which could be associated with the metabolic improvements seen after surgery. Few studies have been conducted in Latin American populations, such as Mexico, where obesity prevalence is above 30% in the adult population. Thus, the aim of this study was to characterize the changes in the gut microbiota structure in a Mexican cohort before and after RYGB and to explore whether surgery-related changes in the microbial community were associated with weight loss. METHODS: Biological samples from patients who underwent RYGB were examined before and 12 months after surgery. Fecal microbiota characterization was performed through 16S rRNA sequencing. RESULTS: Twenty patients who underwent RYGB showed a median excess weight loss of 66.8% 12 months after surgery. Surgery increased alpha diversity estimates (Chao, Shannon index, and observed operational taxonomic units, p < 0.05) and significantly altered gut microbiota composition. Abundance of four genera was significantly increased after surgery: Oscillospira, Veillonella, Streptococcus, and an unclassified genus from Enterobacteriaceae family (PFDR < 0.1). The change in Veillonella abundance was associated with lower excess weight loss (rho = -0.446, p = 0.063) and its abundance post-surgery with a greater BMI (rho = 0.732, p = 5.4 × 10-4). In subjects without type 2 diabetes, lower bacterial richness and diversity before surgery were associated with a greater Veillonella increase after surgery (p < 0.05), suggesting that a lower bacterial richness before surgery could favor the bloom of certain oral-derived bacteria that could negatively impact weight loss. CONCLUSION: Presurgical microbiota profile may favor certain bacterial changes associated with less successful results.

The Prognostic Role of Preoperative Hematological and Inflammatory Indices in Canine Appendicular Osteosarcoma.

Hematological indices play a prognostic role in human osteosarcoma (OSA), but data are limited in dogs. The aim of this retrospective multicentric cohort study was to investigate the prognostic significance of pre-operative hematological/inflammatory indices in a cohort of client-owned dogs with appendicular OSA receiving standardized treatment. Cut-offs associated with progression-free survival (PFS) for pre-operative hematological values/ratios were established using the minimal p-value approach. Historical prognostic factors were also assessed. Statistical analyses were performed for the whole population and after the exclusion of sighthounds. Fifty-nine dogs were included (13 were sighthounds). Multivariable analysis revealed that a low neutrophil count (<4.37 × 109/L, HR0.28, CI 95% 0.13-0.61, p = 0.001), a high red blood cell count (≥7.91, HR3.5, CI 95% 1.56-7.9, p = 0.002), and a proximal humerus location (HR3.0, CI 95% 1.48-6.1, p = 0.002) were associated with shorter PFS. In the sighthound-only population, only OSA location was significantly associated with PFS in univariable analysis. When sighthounds were excluded, a low neutrophil count, a low monocyte count, and a proximal humerus location were associated with shorter PFS, in multivariable analysis. Neutrophil count and possibly monocyte and red blood cell counts can be useful prognostic markers in canine OSA treated with amputation and adjuvant carboplatin. However, not all indices are appropriate in sighthounds.

Beneficial Effects of Plant-Based Diets on Skin Health and Inflammatory Skin Diseases.

The human skin is a crucial organ that protects the organism from the outer environment. Skin integrity and health depend on both extrinsic and intrinsic factors. Intrinsic factors such as aging and genetic background contribute to weakened skin and disease susceptibility. Meanwhile, extrinsic factors including UV radiation, pollution, smoking, humidity, and poor diet also affect skin health and disease. On the other hand, healthy dietary patterns such as plant-based diets have gained popularity as a complementary therapy for skin health. A plant-based diet is defined as all diets based on plant foods, including an abundance of vegetables, fruits, beans, lentils, legumes, nuts, seeds, fungi, and whole grains, with limited or no animal products or processed foods. However, some authors also exclude or limit processed foods in the definition. Recent research has shown that these diets have beneficial effects on inflammatory skin diseases. This review explored the beneficial effects of plant-based diets on inflammatory skin diseases and plant-based functional foods on healthy skin. In conclusion, plant-based diets and plant-based functional foods may have beneficial effects on skin health through the gut microbiome.

Several challenges associated with the anesthetic management of Emery-Dreifuss muscular dystrophy patients: case report

Abstract Emery-Dreifuss Muscular Dystrophy is a very rare type of muscular dystrophy, associated with contractures, atrophy, and muscle weakness, besides cardiomyopathy with severe arrhythmias. Published studies focusing on this disorder are scarce. We describe the anesthetic management of a male patient with Emery-Dreifuss Muscular Dystrophy, to be submitted to umbilical and inguinal hernioplasty and hydrocele repair under epidural anesthesia. The anesthesia approach enabled us to circumvent the patient's susceptibility to malignant hyperthermia and his potentially difficult airway, in addition to maintaining hemodynamic stability. The day after surgery the patient resumed walking, and two days later he was discharged from the hospital.

Patterns of nodal metastases, biological behaviour and prognosis of canine mast cell tumours of the pinna: A multi-institutional retrospective study.

Canine cutaneous mast cell tumours (cMCTs) of the pinna have been associated with an aggressive biological behaviour, although data remain scarce. The knowledge acquired over the past years on histologic gradings, and the value of lymph node (LN) staging, may help in better characterizing this anatomical presentation. The first aim was to describe the frequency, location, and histologic appearance of LN metastases in cMCT of the pinna. A second aim was to evaluate prognosis. Medical records of dogs with cMCT of the pinna, that underwent tumour and sentinel (SLN) or regional LN (RLN) excision, were reviewed. The influence of potential prognostic variables on time to progression (TTP) and tumour-specific survival (TSS) was investigated. Thirty-nine dogs were included: 19 (48.7%) had Kiupel high-grade (K-HG) and 20 (51.3%) had low-grade (K-LG) MCTs. Eighteen (46.1%) dogs underwent SLN mapping: the superficial cervical LN was at least one of SLN in 17 (94.4%) cases. Twenty-two (56.4%) dogs had LN metastases; the superficial cervical LN was always involved. On multivariable analysis, only K-HG was associated with increased risk of progression (p = .043) and tumour-related death (p = .021). Median TTP and TSS were 270 and 370 days in K-HG, respectively; these were not reached in dogs with K-LG tumours (p < .01). cMCTs of the pinna are often K-HG and are also associated with a higher frequency of LN metastasis; however, we confirmed the independent prognostic value of histologic grading. A multimodal treatment may lead to favourable long-term outcome. Moreover, the superficial cervical LN is most often the SLN.

Interstitial Macrophages Lead Early Stages of Bleomycin-Induced Lung Fibrosis and Induce Fibroblasts Activation.

A progressive fibrosing phenotype is critical in several lung diseases. It is irreversible and associated with early patient mortality. Growing evidence has revealed pulmonary macrophages' role as modulators of the fibrotic processes. The proportion, phenotype, and function of alveolar (AM) and interstitial macrophages (IM) at the early stages of bleomycin-induced pulmonary fibrosis have not been clearly described. In this way, our study aimed to characterize these macrophage populations and investigate the effect on fibroblast activation. C57BL/6 mice were intratracheally injected with bleomycin and were sacrificed at day 3, 5, and 7 for the performance of flow cytometry and fluorescent-activated cell sorting analysis for protein and gene expression quantification. After bleomycin administration, the proportion of IM was significantly higher than that of AM, which showed a decay during the inflammatory phase, and peaked at day 7. At day 7 of the inflammatory phase, AM started shifting their phenotype from M1-like towards M2, while IM showed a M2-like phenotype. Conditioned medium derived from IM sorted at day 7 induced fibroblast activation and differentiation in myofibroblasts in vitro. Our findings indicate that IM are the largest macrophage population at the early stages of experimental pulmonary fibrosis and are secreted mediators able to activate fibroblasts, pointing to macrophage modulation as a potential therapeutic strategy to restrain progressive fibrosing lung disorders.

A metagenomic study identifies a Prevotella copri enriched microbial profile associated with non-alcoholic steatohepatitis in subjects with obesity.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease. Increasing evidence indicates that the gut microbiota can play an important role in the pathophysiology of NAFLD. Recently, several studies have tested the predictive value of gut microbiome profiles in NAFLD progression; however, comparisons of microbial signatures in NAFLD or non-alcoholic steatohepatitis (NASH) have produced discrepant results, possibly due to ethnic and environmental factors. Thus, we aimed to characterize the gut metagenome composition of patients with fatty liver disease. METHODS: Gut microbiome of 45 well-characterized patients with obesity and biopsy-proven NAFLD was evaluated using shot-gun sequencing: 11 non-alcoholic fatty liver controls (non-NAFL), 11 with fatty liver, and 23 with NASH. RESULTS: Our study showed that Parabacteroides distasonis and Alistipes putredenis were enriched in fatty liver but not in NASH patients. Notably, in a hierarchical clustering analysis, microbial profiles were differentially distributed among groups, and membership to a Prevotella copri dominant cluster was associated with a greater risk of developing NASH. Functional analyses showed that although no differences in LPS biosynthesis pathways were observed, Prevotella-dominant subjects had higher circulating levels of LPS and a lower abundance of pathways encoding butyrate production. CONCLUSIONS: Our findings suggest that a Prevotella copri dominant bacterial community is associated with a greater risk for NAFLD disease progression, probably linked to higher intestinal permeability and lower capacity for butyrate production.

Timely adjuvant chemotherapy improves outcome in dogs with non-metastatic splenic hemangiosarcoma undergoing splenectomy.

Timely delivery of adjuvant chemotherapy has been shown to be advantageous in many human cancers and canine osteosarcoma. Adjuvant chemotherapy has been shown to improve outcome for canine splenic hemangiosarcoma. The aim of this retrospective study was to investigate whether timely adjuvant chemotherapy administration resulted in better outcome in dogs with non-metastatic splenic hemangiosarcoma undergoing splenectomy. Medical records were searched for dogs with non-metastatic, splenic hemangiosarcoma that received splenectomy and adjuvant chemotherapy. The number of days from surgery to the first chemotherapy dose (StoC) was evaluated to identify the cut-off value associated with the best survival advantage. StoC and other possible prognostic factors were tested for influence on time to metastasis (TTM) and overall survival (OS). Seventy dogs were included. Median StoC was 20 days (range: 4-70). The time interval associated with the greatest survival benefit was 21 days. Median TTM and OS of dogs with StoC ≤ 21 days were significantly longer than those with StoC >21 days (TTM: 163 vs. 118 days, p = .001; OS: 238 vs. 146 days, p < .001). On multivariable analysis, StoC >21 days was the only variable significantly associated with increased risk of tumour progression (HR 2.1, p = .010) and death (HR 2.3; p = .008). Starting adjuvant chemotherapy within 21 days of surgery may be associated with a survival benefit in dogs with non-metastatic splenic hemangiosarcoma, possibly due to the early targeting of newly recruited metastatic cells after surgery.

Several challenges associated with the anesthetic management of Emery-Dreifuss muscular dystrophy patients: case report.

Emery-Dreifuss Muscular Dystrophy is a very rare type of muscular dystrophy, associated with contractures, atrophy, and muscle weakness, besides cardiomyopathy with severe arrhythmias. Published studies focusing on this disorder are scarce. We describe the anesthetic management of a male patient with Emery-Dreifuss Muscular Dystrophy, to be submitted to umbilical and inguinal hernioplasty and hydrocele repair under epidural anesthesia. The anesthesia approach enabled us to circumvent the patient...s susceptibility to malignant hyperthermia and his potentially difficult airway, in addition to maintaining hemodynamic stability. The day after surgery the patient resumed walking, and two days later he was discharged from the hospital.

Approach and anesthetic management for kidney transplantation in a patient with bilateral lung transplantation: case report

Abstract Lung transplantation is the last resort for end-stage lung disease treatment. Due to increased survival, lung recipients present an increased likelihood to be submitted to anesthesia and surgery. This case report describes a 23-year-old female patient with history of lung transplantation for cystic fibrosis, with multiple complications, and chronic kidney disease, and who underwent kidney transplantation under general anesthesia. Understanding the pathophysiology and changes related to immunosuppressive therapy is essential to anesthetic technique planning and safety, and for perioperative management. The success of both anesthesia and surgery requires a qualified multidisciplinary team due to the rarity of the clinical scenario and high incidence of associated morbidity and mortality.

Gut microbiota composition after a dietary and physical activity intervention: a pilot study in Mexican children with obesity.

BACKGROUND: Gut microbiota is a complex organized collection of microorganisms that confers multiple metabolic advantages to the host. The reduced diversity and proportion of specific gut microbial species have been associated with obesity and metabolic disorders. Multidimensional interventions, including modifications in dietary and physical activity habits, are associated with favorable changes in microbiota composition. This pilot study aimed to evaluate changes in the gut microbiota composition of Mexican children with obesity before and after a 6-week multidimensional intervention. METHODS: Blood and stool samples were collected, and anthropometric measurements were obtained from six children with obesity before and after the intervention. The intervention consisted of modeling a hypo energetic diet and giving nutritional and physical activation recommendations. DNA from stool samples was used to characterize gut microbial composition by sequencing the 16S rRNA gene. RESULTS: The decrease in waist circumference was associated with increased Odoribacter relative abundance. However, gut microbiota composition and diversity remained unchanged. CONCLUSIONS: Although no modifications in the body mass index, body fat, composition, or diversity of the gut microbiota were observed with the intervention, it was possible to associate the reduction in waist circumference with the presence of Odoribacter after a multidimensional intervention in Mexican children with obesity.

INTRODUCCIÓN: La microbiota intestinal es un conjunto de microorganismos organizados de forma compleja que confieren múltiples ventajas metabólicas al hospedero. La reducida diversidad y la proporción de ciertas especies sobre otras se ha asociado con obesidad y enfermedades metabólicas. Las intervenciones multidimensionales, que incluyen modificaciones en los hábitos alimentarios y de actividad física, se asocian con cambios favorables en la composición de la microbiota. El objetivo de este estudio piloto fue evaluar la composición de la microbiota intestinal de niños mexicanos con obesidad, antes y después de una intervención multidimensional de seis semanas de duración. MÉTODOS: Se tomaron muestras de sangre y de heces y se realizaron las mediciones antropométricas de seis niños con obesidad, antes y después de la intervención. La intervención consistió en modelar una dieta hipoenergética y dar recomendaciones nutricias y de actividad física. A partir del DNA de las muestras de heces se realizó la caracterización de la microbiota intestinal por secuenciación del gen 16S del RNAr. RESULTADOS: La disminución de la circunferencia de cintura se asoció con un aumento en la abundancia del género Odoribacter. Sin embargo, no se encontraron cambios en la composición de la microbiota intestinal. CONCLUSIONES: A pesar de que la intervención no modificó el índice de masa corporal, masa grasa, composición ni diversidad de la microbiota intestinal, sí se logró asociar la reducción de la circunferencia de cintura con la abundancia de Odoribacter en el presente estudio piloto en niños mexicanos con obesidad.

Gut microbiota composition after a dietary and physical activity intervention: a pilot study in Mexican children with obesity / Efecto de una intervención nutricia y de actividad física sobre la composición de la microbiota intestinal: un estudio piloto en niños mexicanos con obesidad

Abstract Background: Gut microbiota is a complex organized collection of microorganisms that confers multiple metabolic advantages to the host. The reduced diversity and proportion of specific gut microbial species have been associated with obesity and metabolic disorders. Multidimensional interventions, including modifications in dietary and physical activity habits, are associated with favorable changes in microbiota composition. This pilot study aimed to evaluate changes in the gut microbiota composition of Mexican children with obesity before and after a 6-week multidimensional intervention. Methods: Blood and stool samples were collected, and anthropometric measurements were obtained from six children with obesity before and after the intervention. The intervention consisted of modeling a hypo energetic diet and giving nutritional and physical activation recommendations. DNA from stool samples was used to characterize gut microbial composition by sequencing the 16S rRNA gene. Results: The decrease in waist circumference was associated with increased Odoribacter relative abundance. However, gut microbiota composition and diversity remained unchanged. Conclusions: Although no modifications in the body mass index, body fat, composition, or diversity of the gut microbiota were observed with the intervention, it was possible to associate the reduction in waist circumference with the presence of Odoribacter after a multidimensional intervention in Mexican children with obesity.

Resumen Introducción: La microbiota intestinal es un conjunto de microorganismos organizados de forma compleja que confieren múltiples ventajas metabólicas al hospedero. La reducida diversidad y la proporción de ciertas especies sobre otras se ha asociado con obesidad y enfermedades metabólicas. Las intervenciones multidimensionales, que incluyen modificaciones en los hábitos alimentarios y de actividad física, se asocian con cambios favorables en la composición de la microbiota. El objetivo de este estudio piloto fue evaluar la composición de la microbiota intestinal de niños mexicanos con obesidad, antes y después de una intervención multidimensional de seis semanas de duración. Métodos: Se tomaron muestras de sangre y de heces y se realizaron las mediciones antropométricas de seis niños con obesidad, antes y después de la intervención. La intervención consistió en modelar una dieta hipoenergética y dar recomendaciones nutricias y de actividad física. A partir del DNA de las muestras de heces se realizó la caracterización de la microbiota intestinal por secuenciación del gen 16S del RNAr. Resultados: La disminución de la circunferencia de cintura se asoció con un aumento en la abundancia del género Odoribacter. Sin embargo, no se encontraron cambios en la composición de la microbiota intestinal. Conclusiones: A pesar de que la intervención no modificó el índice de masa corporal, masa grasa, composición ni diversidad de la microbiota intestinal, sí se logró asociar la reducción de la circunferencia de cintura con la abundancia de Odoribacter en el presente estudio piloto en niños mexicanos con obesidad.

Association of Gut Microbiota with Atherogenic Dyslipidemia, and Its Impact on Serum Lipid Levels after Bariatric Surgery.

Gut microbiota has been suggested to modulate circulating lipids. However, the relationship between the gut microbiota and atherogenic dyslipidemia (AD), defined as the presence of both low HDL-C and hypertriglyceridemia, is not fully understood. Moreover, because obesity is among the main causes of secondary AD, it is important to analyze the effect of gut microbiota composition on lipid profiles after a weight loss intervention. We compared the microbial diversity and taxonomic composition in patients with AD (n = 41) and controls (n = 38) and sought correlations of genera abundance with serum lipid levels in 20 patients after weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Gut microbiota composition was profiled using next-generation sequencing of 16S rRNA. Gut microbiota diversity was significantly lower in atherogenic dyslipidemia. Moreover, relative abundance of two genera with LDA score >3.5 (Megasphaera and LPS-producing Escherichia-Shigella), was significantly higher in AD subjects, while the abundance of four short chain fatty acids (SCFA) producing-genera (Christensenellaceae R-7, Ruminococcaceae UCG-014; Akkermansia and [Eubacterium] eligens group) was significantly higher in controls. Notably, [Eubacterium] eligens group abundance was also significantly associated with higher HDL-C levels in RYGB patients one year after surgery. Although dietary polyunsaturated fatty acid/saturated fatty acid (PUFA/SFA) ratio and PUFA intake were higher in controls than in AD subjects, of the four genera differentiated in cases and controls, only Akkermansia abundance showed a positive and significant correlation with PUFA/SFA ratio. Our results suggest that SCFA-producing bacteria promote a healthy lipid homeostasis, while the presence of LPS-producing bacteria such Escherichia-Shigella may contribute to the development of atherogenic dyslipidemia.

Prevalence and Predictors of Abdominal Aorta Calcification in Patients With Psoriasis-A Case Control Study.

Background: Psoriasis is associated with a high prevalence of cardiovascular disease in Caucasians, but only a few studies from sub-Saharan Africa have investigated the prevalence of cardiovascular disease in patients with psoriasis. Abdominal aortic calcification (AAC) is a strong predictor of future cardiovascular events and all-cause mortality in the general population. We investigated the prevalence and risk factors for AAC in a predominantly non-Caucasian cohort of South African patients with psoriasis. Methods: A cross-sectional case-control study of adult psoriasis patients (n = 69) and controls (n = 80), matched for gender, ethnicity and body mass index, attending tertiary Dermatology and Rheumatology clinics in Johannesburg, South Africa. Demographic, anthropometric, clinical and biochemical data were recorded. All participants underwent non-contrast abdominal CT scans. Images were assessed for AAC at the supra-coeliac aorta, supra-mesenteric aorta and aortic bifurcation using Horos DICOM viewer software. Results: Abdominal aortic calcification at any site was more prevalent in the psoriasis than control group (47.8% vs 22.5%, p < 0.005). The aortic bifurcation was the commonest site for AAC in both groups, but more prevalent in the psoriasis group (42.0% vs 21.3%, p < 0.005). The psoriasis group was also more likely to smoke, have hypertension and type 2 diabetes (56.5% vs 25.0%, p < 0.005; 72.0% vs 55.0%, p < 0.005; 24.6% vs 3.80%, p < 0.0005, respectively). Multivariable logistic regression analysis demonstrated that age, smoking and type 2 (T2DM) diabetes were independently associated with AAC (odds ratio (95% CIs): 1.16 (1.07, 1.20), 4.30 (2.15, 8.61) and 3.45 (1.09, 15.7) respectively), but psoriasis was not. Forward regression analysis demonstrated that smoking attenuated the association of psoriasis with AAC. Conclusion: Our findings show AAC to be more common in psoriasis patients compared to controls. Age, T2DM and smoking were independent predictors of AAC. Smoking cessation is essential in psoriatic patients to reduce the risk of cardiovascular events. The clinical utility of AAC detection by CT imaging to risk stratify for hard cardiovascular outcomes needs to be explored.

Lysyl Oxidases Expression and Breast Cancer Progression: A Bioinformatic Analysis.

LOX (Lysyl oxidase) and LOX like 1-4 (LOXL1-4) are amine oxidases that catalyse the cross-linking of elastin and collagen in the extracellular matrix (ECM). This activity can facilitate cell migration and the formation of metastases. Consequently, inhibition of these enzymes and, in particular of LOXL2, has been suggested as a therapeutic strategy to prevent breast cancer metastasis. Although medicinal chemistry studies have struggled to specifically inhibit LOXL2, the importance of selectivity in this context is not clear. To explore the role of each LOX in breast cancer and consequently their potential as biomarkers or therapeutic targets, a bioinformatic-based approach was followed. The expression profile of LOXs, the putative associations among mRNA expression from each LOX and clinical observations, the correlation between expression of LOX enzymes and other genes, and the association between expression of LOXs and the tumour infiltrates were assessed for breast cancer. Overall, the patient outcome and the characteristics of breast tumours with LOX, LOXL1 and LOXL2 upregulation is distinct from those with high expression of LOXL3 and LOXL4. Additionally, the expression correlation between LOXs and other genes involved in cellular processes relevant for cancer biology, also reveals a similar trend for LOX, LOXL1 and LOX2. This work further supports the relevance of LOXL2 as a breast cancer progression biomarker and therapeutic target. We speculate that while the impact of LOXL3 inhibition may vary with breast cancer subtype, the therapeutical inhibition of LOX, LOXL1 and LOXL2 but not of LOXL4 may be the most beneficial.

Isotretinoin treatment of 12 dogs with epitheliotropic lymphoma.

BACKGROUND: Epitheliotropic lymphoma is an uncommon cutaneous malignancy of T lymphocytes. Limited information is available regarding the treatment and outcome of dogs with this disease. OBJECTIVES: To evaluate the treatment outcome and toxicity profile of isotretinoin in dogs with epitheliotropic lymphoma. ANIMALS: Twelve dogs with a diagnosis of epitheliotropic lymphoma were included. MATERIALS AND METHODS: A medical database was searched for dogs diagnosed with epitheliotropic lymphoma and treated with isotretinoin between 2010 and 2021. Diagnosis, treatment details and tumour response were recorded for 12 dogs. RESULTS: All lesions resolved in four of 12 (33%) treated dogs. Lesions visibly improved in a further three dogs, giving a response rate of 58%. Two dogs' lesions remained unchanged and three progressed despite therapy. Adverse effects occurred in three dogs (25%), all of which were rapidly resolving or not affecting quality of life. CONCLUSION: Isotretinoin treatment was a well-tolerated and effective treatment for canine epitheliotropic lymphoma.

Contexte - Le lymphome épithéliotrope est une tumeur maligne cutanée peu fréquente des lymphocytes T. Peu d'informations sont disponibles concernant le traitement et les résultats des chiens atteints de cette maladie. Objectifs - Évaluer les résultats du traitement et le profil de toxicité de l'isotrétinoïne chez les chiens atteints de lymphome épithéliotrope. Animaux - Douze chiens avec un diagnostic de lymphome épithéliotrope ont été inclus. Matériels et méthodes - Une base de données médicale a été recherchée pour les chiens diagnostiqués avec un lymphome épithéliotrope et traités à l'isotrétinoïne entre 2010 et 2021. Le diagnostic, les détails du traitement et la réponse tumorale ont été enregistrés pour 12 chiens. Résultats - Toutes les lésions ont disparu chez quatre des 12 (33 %) chiens traités. Les lésions se sont visiblement améliorées chez trois autres chiens, donnant un taux de réponse de 58 %. Les lésions de deux chiens sont restées stables et trois ont progressé malgré la thérapie. Des effets indésirables sont survenus chez trois chiens (25 %), qui se résolvaient tous rapidement ou n'affectaient pas la qualité de vie. Conclusion - Le traitement à l'isotrétinoïne a été un traitement bien toléré et efficace du lymphome épithéliotrope canin.

Introducción - El linfoma epiteliotrópico es una neoplasia maligna cutánea poco frecuente de linfocitos T. Se dispone de información limitada sobre el tratamiento y el resultado del mismo en perros con esta enfermedad. Objetivos- evaluar el resultado del tratamiento y el perfil de toxicidad de la isotretinoína en perros con linfoma epiteliotrópico. Animales- se incluyeron 12 perros con diagnóstico de linfoma epiteliotrópico. Materiales y métodos- se buscó en una base de datos médica perros diagnosticados con linfoma epiteliotrópico y tratados con isotretinoína entre 2010 y 2021. Se reciplaron datos del diagnóstico, los detalles del tratamiento y la respuesta del tumor en 12 perros. Resultados- todas las lesiones se resolvieron en cuatro de 12 (33 %) perros tratados. Las lesiones mejoraron visiblemente en otros tres perros, con una tasa de respuesta del 58%. Las lesiones de dos perros permanecieron estables y tres progresaron a pesar de la terapia. Efectos adversos fueron reportados en tres perros (25%), todos los cuales se resolvieron rápidamente o no afectaron a la calidad de vida. Conclusión- el tratamiento con isotretinoína fue bien tolerado y eficaz para el linfoma epiteliotrópico canino.

Contexto - O linfoma epiteliotrópico é uma neoplasia cutânea de linfócitos T incomum. As informações disponíveis sobre o tratamento e evolução de cães com essa doença são limitadas. Objetivos - Avaliar a resposta ao tratamento e o perfil de toxicidade da isotretinoína em cães com linfoma epiteliotrópico. Animais - Doze cães com linfoma epiteliotrópico foram incluídos. Materiais e métodos - Pesquisou-se em um banco de dados médico os cães diagnosticados com linfoma epiteliotrópico e tratados com isotretinoína entre 2010 e 2021. Diagnóstico, detalhes do tratamento e resposta tumoral foram registrados para 12 cães. Resultados - Todas as lesões se resolveram em quatro de 12 (33%) cães. As lesões melhoraram visivelmente em outros três cães, gerando uma taxa de resposta de 58%. As lesões de dois cães permaneceram estáveis e três progrediram apesar da terapia. Ocorreram efeitos adversos em três cães (25%), mas todos apresentaram resolução rápida ou não tiveram alteração na qualidade de vida. Conclusão - O tratamento com isotretinoína foi bem tolerado e eficaz para o linfoma epiteliotrópico canino.

Approach and anesthetic management for kidney transplantation in a patient with bilateral lung transplantation: case report.

Lung transplantation is the last resort for end-stage lung disease treatment. Due to increased survival, lung recipients present an increased likelihood to be submitted to anesthesia and surgery. This case report describes a 23-year-old female patient with history of lung transplantation for cystic fibrosis, with multiple complications, and chronic kidney disease, and who underwent kidney transplantation under general anesthesia. Understanding the pathophysiology and changes related to immunosuppressive therapy is essential to anesthetic technique planning and safety, and for perioperative management. The success of both anesthesia and surgery requires a qualified multidisciplinary team due to the rarity of the clinical scenario and high incidence of associated morbidity and mortality.