[Weight gain during menopause: physiology and practical implications]. / Prise de poids pendant la ménopause : physiologie et implications pratiques.

Fluctuations in sex hormones at different stages of reproductive life, such as the menopausal transition, have been suggested as players in weight regulation. Indeed, the transition from a predominantly estrogenic state to an androgenic state characteristic of the menopausal transition contributes to changes in body composition with accumulation of fat and simultaneous loss of lean mass. However, whether these changes contribute to the weight gain remains debatable. Other physiological and psychosocial factors come into play. It is therefore important to offer individualized support with the objective to minimize the risk of weight gain and associated complications.

La fluctuation des hormones sexuelles à différentes étapes de la vie reproductive, telles que la transition ménopausique, a été proposée comme une des composantes de la régulation de poids. Effectivement, le passage d'un état principalement œstrogénique à un état androgénique, caractéristique de la transition ménopausique, contribue à des modifications de la composition corporelle avec une accumulation de graisse et une perte simultanée de masse maigre. Cependant, la question de savoir si ces changements contribuent à une prise de poids reste discutable. L'obésité est une maladie multifactorielle et d'autres facteurs d'ordre physiologique et psychosociaux rentrent en jeu. Il est donc important d'offrir un accompagnement individualisé aux femmes concernées pour les aider à minimiser le risque de prise pondérale et des complications associées.

Mustn1 is a smooth muscle cell-secreted microprotein that modulates skeletal muscle extracellular matrix composition.

OBJECTIVE: Skeletal muscle plasticity and remodeling are critical for adapting tissue function to use, disuse, and regeneration. The aim of this study was to identify genes and molecular pathways that regulate the transition from atrophy to compensatory hypertrophy or recovery from injury. Here, we have used a mouse model of hindlimb unloading and reloading, which causes skeletal muscle atrophy, and compensatory regeneration and hypertrophy, respectively. METHODS: We analyzed mouse skeletal muscle at the transition from hindlimb unloading to reloading for changes in transcriptome and extracellular fluid proteome. We then used qRT-PCR, immunohistochemistry, and bulk and single-cell RNA sequencing data to determine Mustn1 gene and protein expression, including changes in gene expression in mouse and human skeletal muscle with different challenges such as exercise and muscle injury. We generated Mustn1-deficient genetic mouse models and characterized them in vivo and ex vivo with regard to muscle function and whole-body metabolism. We isolated smooth muscle cells and functionally characterized them, and performed transcriptomics and proteomics analysis of skeletal muscle and aorta of Mustn1-deficient mice. RESULTS: We show that Mustn1 (Musculoskeletal embryonic nuclear protein 1, also known as Mustang) is highly expressed in skeletal muscle during the early stages of hindlimb reloading. Mustn1 expression is transiently elevated in mouse and human skeletal muscle in response to intense exercise, resistance exercise, or injury. We find that Mustn1 expression is highest in smooth muscle-rich tissues, followed by skeletal muscle fibers. Muscle from heterozygous Mustn1-deficient mice exhibit differences in gene expression related to extracellular matrix and cell adhesion, compared to wild-type littermates. Mustn1-deficient mice have normal muscle and aorta function and whole-body glucose metabolism. We show that Mustn1 is secreted from smooth muscle cells, and that it is present in arterioles of the muscle microvasculature and in muscle extracellular fluid, particularly during the hindlimb reloading phase. Proteomics analysis of muscle from Mustn1-deficient mice confirms differences in extracellular matrix composition, and female mice display higher collagen content after chemically induced muscle injury compared to wild-type littermates. CONCLUSIONS: We show that, in addition to its previously reported intracellular localization, Mustn1 is a microprotein secreted from smooth muscle cells into the muscle extracellular space. We explore its role in muscle ECM deposition and remodeling in homeostasis and upon muscle injury. The role of Mustn1 in fibrosis and immune infiltration upon muscle injury and dystrophies remains to be investigated, as does its potential for therapeutic interventions.

Multiple myeloma in dogs: Use of the cell block technique as a new diagnostic tool.

BACKGROUND: The diagnosis of multiple myeloma (MM) in dogs may be challenging and complex. The cell blocks are a diagnostic technique that allows the characterization of neoplastic cells and, therefore, might help in the diagnosis of atypical MM. OBJECTIVE: The objective of the present work is to describe three clinical cases in which the cell blocks and immunohistochemistry contributed to the definitive diagnosis of canine MM. METHODS: Three dogs, one female and two males, with different clinical signs, were presented for consultation with anemia, hyperproteinemia with monoclonal gammopathy, and the presence of plasmacytosis in the bone marrow. Cytologic analysis of the spleen was performed in two dogs and was suggestive of the presence of lymphocytes or plasma cells of a neoplastic nature in one of the cases and plasma cell hyperplasia associated with extramedullary hematopoiesis in the other. Given the hypotheses of lymphoid neoplasms with a plasma cell phenotype, cell blocks from aspiration punctures were performed for immunohistochemical analysis with anti-CD3, CD20, CD79αcy, PAX5, and MUM1 antibodies. RESULTS: The results revealed positive staining for MUM1 in 80% of the cells in the spleen cell block and for CD20 and MUM1 in 70% of the cells in the bone marrow cell blocks, with negative staining for the other antibodies. The immunophenotyping results allowed the diagnosis of MM in the three cases and excluded other lymphoid neoplasms. CONCLUSIONS: This work reinforces the importance of using cell blocks in the diagnosis of neoplasms by demonstrating their potential to aid the diagnosis of MM.

Loss of RAS Mutations in Liquid Biopsies of Patients With Multi-Treated Metastatic Colorectal Cancer.

BACKGROUND: Liquid biopsy (LB) is a non-invasive tool to evaluate the heterogeneity of tumors. Since RAS mutations (RAS-mut) play a major role in resistance to antiepidermal growth factor receptor inhibitors (EGFR) monoclonal antibodies (Mabs), serial monitoring of RAS-mut with LB may be useful to guide treatment. The main aim of this study was to evaluate the prognostic value of the loss of RAS-mut (NeoRAS-wt) in LB, during the treatment of metastatic colorectal cancer (mCRC). METHODS: A retrospective study was conducted on patients with mCRC between January 2018 and December 2021. RAS-mut were examined in tissue biopsy, at mCRC diagnosis, and with LB, during treatment. RESULTS: Thirty-nine patients with RAS-mut mCRC were studied. LB was performed after a median of 3 lines (0-7) of systemic treatment including anti-vascular endothelial growth factor (anti-VEGF) Mabs. NeoRAS-wt was detected in 13 patients (33.3%); 9 (69.2%) of them received further treatment with anti-EGFR Mabs with a disease control rate of 44.4%. Median overall survival (OS), from the date of LB testing, was 20 months in the NeoRAS-wt group and 9 months in the persistent RAS-mut group (log-rank 2.985; P = .08), with a 12-month OS of 84.6% and 57.7%, respectively. NeoRAS-wt was identified as a predictor of survival (HR = 0.29; P = .007), with an 11-month improvement in median OS and a 71% decrease in risk of death, in heavily pretreated patients. CONCLUSIONS: In conclusion, monitoring clonal evolution in mCRC by LB may provide an additional treatment line for patients with NeoRAS-wt in advanced disease.

Redefining Foot Symptoms in a Kidney-Pancreas-Transplanted Type 1 Diabetic Patient: Challenging the Conventional Charcot Foot Diagnosis.

BACKGROUND Acute Charcot foot can be difficult to diagnose, especially because of other alternate diagnoses that can mimic this condition, particularly stress fracture and acute bone and joint infections, which are 2 conditions that require immediate management. Here, we present the case of a patient who received kidney-pancreas-transplantation for type 1 diabetes mellitus, who consulted for right foot pain after walking. CASE REPORT Our patient was a 47-year-old man who had benefited from a kidney-pancreas transplantation in 2014 for type 1 diabetes and terminal kidney failure and was recently followed for a right foot plantar ulcer that was fully healed. He later presented for right foot pain after walking. Clinical examination showed a red, swollen, and warm foot. Blood test results were unremarkable. Imaging (X-ray/MRI) revealed features compatible with acute Charcot foot. The management consisted of prompt right-foot offloading followed by physiotherapy and adapted orthopedic insoles. CONCLUSIONS This case shows the successful treatment of an active phase of Charcot foot, which avoided the classic transition to chronic Charcot foot with severe osteoarticular destruction. Arguments were developed to rule out other possible diagnoses. The underlying mechanisms of Charcot foot in diabetic patients are related to the neurological and micro-vascular complications induced by poor glycemic control, but the mechanisms are unclear. This case report may help clinicians to better understand and consider another less known and less frequent diagnosis when faced with these clinical features.

Panobinostat-loaded folate targeted liposomes as a promising drug delivery system for treatment of canine B-cell lymphoma.

Introduction: Cancer is a major public health problem with over 19 million cases reported in 2020. Similarly to humans, dogs are also largely affected by cancer, with non-Hodgkin's lymphoma (NHL) among the most common cancers in both species. Comparative medicine has the potential to accelerate the development of new therapeutic options in oncology by leveraging commonalities between diseases affecting both humans and animals. Within this context, in the present study, we investigated the potential of panobinostat (Pan)-loaded folate-targeted PEGylated liposomes (FA-PEG-Pan-Lip) for the treatment of canine B-cell lymphoma, while contributing to new perspectives in comparative oncology. Methods and results: Two formulations were developed, namely: PEG-Pan-Lip and FA-PEG-Pan-Lip. Firstly, folate receptor expression in the CLBL-1 canine B-cell lymphoma cell line was assessed. After confirming receptor expression, both Pan-loaded formulations (PEG-Pan-Lip, FA-PEG-Pan-Lip) demonstrated dose-dependent inhibitory effects on CLBL-1 cell proliferation. The FA-PEG-Pan-Lip formulation (IC50 = 10.9 ± 0.03 nM) showed higher cytotoxicity than the non-targeted PEG-Pan-Lip formulation (IC50 = 12.9 ± 0.03 nM) and the free panobinostat (Pan) compound (IC50 = 18.32±0.03 nM). Moreover, mechanistically, both Pan-containing formulations induced acetylation of H3 histone and apoptosis. Flow cytometry and immunofluorescence analysis of intracellular uptake of rhodamine-labeled liposome formulations in CLBL-1 cells confirmed cellular internalization of PEG-Lip and FA-PEG-Lip formulations and higher uptake profile for the latter. Biodistribution studies of both radiolabeled formulations in CD1 and SCID mice revealed a rapid clearance from the major organs and a 1.6-fold enhancement of tumor uptake at 24 h for 111In-FA-PEG-Pan-Lip (2.2 ± 0.1 %ID/g of tumor) compared to 111In-PEG-Pan-Lip formulation (1.2±0.2 %ID/g of tumor). Discussion: In summary, our results provide new data validating Pan-loaded folate liposomes as a promising targeted drug delivery system for the treatment of canine B-cell lymphoma and open innovative perspectives for comparative oncology.

The Influence of Lockdown Due to the COVID-19 Pandemic on Weight Management in Patients With Obesity in Portugal.

INTRODUCTION: Obesity is a chronic and multifactorial disease, and the COVID-19 pandemic and lockdown have led to changes in the lifestyle habits of those patients. This study aimed to compare compliance with dietary and lifestyle measures, physical activity, mental health status, and motivation to lose weight during the pandemic in these patients. METHODS: An observational study was conducted, which included 63 patients over 18 years old who were followed in the outpatient setting through obesity medical appointments and who agreed to answer a questionnaire. RESULTS: We found that the majority of patients lost weight during the pandemic (61.7%), associating it with a 68% change in dietary habits. Regarding physical activity, there was a 34.9% reduction in its practice among those who used to exercise before the pandemic. Moreover, 52.4% felt more anxious and 44.4% felt sadder during the lockdown. DISCUSSION: The weight loss reported in our study seems to be related to a decrease in the consumption of carbohydrates and snacks and a lower percentage of those who relied on takeaways. Additionally, we hypothesize a greater number of home-cooked meals. Regarding exercise, the closure of gyms and the limitations imposed on daily life appear to have contributed unfavorably to this matter. Home confinement, loneliness, and a lack of social activities had harmful effects on the mental health of our sample. CONCLUSION: Overall, the hostile influence of the pandemic on mental well-being and exercise habits was evident. Nevertheless, contrary to our expectations, we observed weight loss during the lockdown.

Zfp697 is an RNA-binding protein that regulates skeletal muscle inflammation and regeneration.

Muscular atrophy is a mortality risk factor that happens with disuse, chronic disease, and aging. Recovery from atrophy requires changes in several cell types including muscle fibers, and satellite and immune cells. Here we show that Zfp697/ZNF697 is a damage-induced regulator of muscle regeneration, during which its expression is transiently elevated. Conversely, sustained Zfp697 expression in mouse muscle leads to a gene expression signature of chemokine secretion, immune cell recruitment, and extracellular matrix remodeling. Myofiber-specific Zfp697 ablation hinders the inflammatory and regenerative response to muscle injury, compromising functional recovery. We uncover Zfp697 as an essential interferon gamma mediator in muscle cells, interacting primarily with ncRNAs such as the pro-regenerative miR-206. In sum, we identify Zfp697 as an integrator of cell-cell communication necessary for tissue regeneration.

Renal Artery Thrombosis After Laparoscopic Living-Donor Nephrectomy: A Case Report.

Renal transplantation is the most successful treatment for end-stage renal disease, and the number of living-donor nephrectomies has been rising over the years due to the advantages it offers over deceased donors. Although this surgery is considered safe, it can be associated with complications amplified by the fact that it is performed on a healthy individual. Renal artery thrombosis is a rare disease that needs prompt diagnosis and treatment to avoid renal function deterioration, which becomes even more important in cases of solitary kidneys. We report the first case of renal artery thrombosis after laparoscopic living-donor nephrectomy treated with catheter-directed thrombolysis.

Morphological and Molecular Identification of Physaloptera alata (Nematoda: Spirurida) in a Booted Eagle (Aquila pennata) from Portugal.

Physaloptera spp. are parasitic nematodes that infect the gastrointestinal tracts of many carnivores and omnivores. Although they are distributed worldwide, Physaloptera spp. have not been studied in raptors in Portugal. In this study, we report Physaloptera alata in a booted eagle (Aquila pennata) in Portugal. Adult nematodes were discovered in the gizzard of a young booted eagle, and morphological features were consistent with those of the genus Physaloptera. DNA was extracted and a PCR assay performed to amplify a region of the 18S small subunit of the ribosomal RNA gene and the cytochrome c oxidase subunit I gene. The resulting PCR products were Sanger-sequenced, and comparison with the available sequences in the GenBank database confirmed the initial morphological classification as Physaloptera sp. Phylogenetic analysis clustered the sequence within the Physaloptera group. The presence of this parasite in raptors from Portugal is of particular importance to wildlife rehabilitation centers, disease ecologists, and wildlife professionals. Furthermore, we produced a new genetic sequence and have added it to the GenBank database of parasites in birds of prey.

[The evolution of the perception of obesity: the "weight" of social norms]. / Évolution de la perception de l'obésité : le « poids ¼ des normes sociales.

The perception of obesity and the ideal body image has evolved over time, largely due to social norms that are not always guided by scientific knowledge. The use of social media for health promotion is an emerging area of investigation. Preliminary research suggests that they have the potential to both serve as a platform for combating the stigma of obesity and promoting positive body image. But there is also evidence that supports the contrary. In particular, the dissemination of digitally altered images that convey ideals of the slim female form can be detrimental to physical and psychological health. Further research is needed to determine how best to use social networks and media as a health promotion tool.

La perception de l'obésité et du corps idéal a bien évolué au cours du temps, liée en grande partie à des normes sociales qui ne sont pas toujours guidées par les connaissances scientifiques. L'utilisation des médias sociaux pour la promotion de la santé est un domaine d'investigation émergent. Les recherches préliminaires suggèrent qu'ils ont le potentiel d'être une plateforme permettant à la fois de lutter contre la stigmatisation de l'obésité et de promouvoir une image corporelle positive. Mais il y a également des preuves qui suggèrent le contraire. Notamment, la diffusion d'images retouchées qui véhiculent des idéaux de minceur irréalistes peut nuire à la santé physique et psychologique. Des recherches supplémentaires sont nécessaires pour déterminer comment utiliser au mieux les réseaux et médias sociaux comme outil de promotion de la santé.

A new definitive host for Moniliformis cestodiformis (Acanthocephala: Moniliformidae): first report of a naturally infected European hedgehog (Erinaceus europaeus).

European hedgehogs, Erinaceus europaeus (Linnaeus, 1758), are small mammals found in western Europe and also in parts of northern Europe. They can be seen in rural, suburban and urban areas, but are usually found in grassland with edge habitats. These animals are omnivorous and serve as definitive or paratenic hosts for several parasites, including acanthocephalans (phylum Acanthocephala). During necropsy of a European hedgehog, a single adult parasite was collected from the intestinal lumen and preserved in 70% ethanol. After morphological evaluation of the specimen, it was identified as Moniliformis cestodiformis (von Linstow, 1904) (Acanthocephala: Moniliformidae). This is the first report of M. cestodiformis in a European hedgehog, as well as in Europe. More epidemiological studies need to be carried out to map the location and prevalence of this parasite in Portugal and the European continent.

Renal cell carcinoma in native kidneys before transplantation - When will we stop waiting?

INTRODUCTION: Kidney transplantation requires immunosuppression, traditionally regarded as a risk factor for progression in all malignancies. Based on the Cincinnati Registry, a waiting period before transplantation is therefore mandatory. However, recent evidence suggests this increased risk is restricted to particular tumors, whereas others like renal cell carcinoma (RCC) are not negatively affected. We aimed to compare oncological outcomes of RCC in native kidneys of end-stage renal disease (ESRD) patients, according to their transplantation or dialysis status. MATERIAL AND METHODS: Retrospective analysis of all ESRD patients diagnosed with RCC between 2010 and 2020 in our center. Recurrence-free survival (RFS) and overall survival (OS) were estimated with Kaplan-Meier curves. Multivariable Cox regression model was used to evaluate their association with kidney transplantation. RESULTS: Clinical and pathological characteristics were similar between groups. Kidney transplant recipients had similar risk of recurrence (hazard ratio [HR] 0.40, 95% confidence interval [CI) 0.04-4.46, p = 0.458) and overall survival (HR 0.34, 95%CI 0.07-1.77, p = 0.202) as dialyzed patients. On multivariable Cox regression model, presence or absence of transplantation was not significantly associated with RFS (p = 0.479) or OS (p = 0.236). Time on dialysis was the only independent predictor of worse survival (HR 1.86, 95%CI 1.18-2.93, p = 0.008). CONCLUSIONS: Most RCC in native kidneys of ESRD patients are low-grade, low-stage and exhibit favourable pathological and outcome features. Immunosuppression does not seem to have an impact on oncological outcomes, but an increased time on dialysis seems to be associated with worse overall survival. Therefore, waiting time for transplantation for these tumors could be reduced.

Enrichment of Brain n-3 Docosapentaenoic Acid (DPA) and Retinal n-3 Eicosapentaenoic Acid (EPA) in Lambs Fed Nannochloropsis oceanica Microalga.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have special physiological functions in both brain and retinal tissues that are related to the modulation of inflammatory processes and direct effects on neuronal membrane fluidity, impacting mental and visual health. Among them, the long-chain (LC) n-3 PUFAs, as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are of special importance. Scarce data are available about the fatty acid (FA) composition of the ruminant brain in response to dietary intervention. However, we decided to examine the brain and retina FA composition of lambs supplemented with an EPA-rich microalga feed for 21 days, as it is known that despite the extensive biohydrogenation of dietary PUFAs in the rumen, ruminants can selectively accumulate some n-3 LC-PUFAs in their brain and retinal tissues. Twenty-eight male lambs were fed a control diet, or the same diet further supplemented with Nannochloropsis sp. microalga. Their brains and retina were collected for FA characterization. Overall, the brain FA profile remained unchanged, with little alteration in omega-3 docosapentaenoic acid (DPA) enhancement in both the hippocampus and prefrontal cortex. Retinal tissues were particularly responsive to the dietary intervention, with a 4.5-fold enhancement of EPA in the freeze-dried-fed lambs compared with the control lambs. We conclude that retinal tissues are sensitive to short-term n-3 PUFA supplementation in lambs.

TIM-3 Is a Potential Immune Checkpoint Target in Cats with Mammary Carcinoma.

Recent findings in human breast cancer (HBC) indicate that T-cell immunoglobulin and mucin-domain-containing molecule-3 (TIM-3)-targeted therapies may effectively activate anticancer immune responses. Although feline mammary carcinoma (FMC) is a valuable cancer model, no studies on TIM-3 have been developed in this species. Thus, we evaluated the expression of TIM-3 by immunohistochemistry in total (t), stromal (s), and intra-tumoral (i) tumor-infiltrating lymphocytes (TILs) and in cancer cells, of 48 cats with mammary carcinoma. In parallel, serum TIM-3 levels were quantified using ELISA and the presence of somatic mutations in the TIM-3 gene was evaluated in 19 tumor samples. sTILs-TIM3+ were more frequent than iTILs-TIM-3+, with the TIM-3 ex-pression in sTILs and cancer cells being associated with more aggressive clinicopathological features. In contrast, the TIM-3 expression in iTILs and tTILs was associated with a more benign clinical course. Moreover, the serum TIM-3 levels were lower in animals with FMC when compared to healthy animals (p < 0.001). Only one somatic mutation was found in the TIM-3 gene, at intron 2, in one tumor sample. Altogether, our results suggest that the expression of TIM-3 among TILs subpopulations and cancer cells may influence the clinical outcome of cats with FMC, in line with the previous reports in HBC.

Co-Expression of T- and B-Cell Markers in a Canine Intestinal Lymphoma: A Case Report.

An 8-year-old female neutered Labrador retriever was presented for a second opinion consultation due to vomiting and lethargy, having failed to respond to symptomatic therapy. Blood analysis revealed hyperbilirubinemia and hypoalbuminemia, associated with hypocobalaminemia. An abdominal ultrasound identified diffused bowel thickening and hypoechoic hepatomegaly. An ultrasound-guided liver fine-needle aspiration was performed for cytology and also for cell block immunocytochemistry. Gastric and duodenal biopsies were collected by gastroduodenoscopy. Liver cytology showed numerous lymphocytes, suggesting lymphoma at the hepatic infiltration stage, and immunocytochemistry in the cell block of the hepatic aspirate indicated co-expression of CD3 and CD20 in the lymphoid cells present. The histopathology of gastric and duodenal biopsies supported the hypothesis of gastrointestinal lymphoma due to heavy lymphoid infiltration of the gastric epithelium and intestinal mucosa, including the villi. Concurrent immunohistochemistry was performed using CD3, CD20, PAX5, and CD79αcy antibodies. Immunomarking was positive for CD3 and CD20, which overlapped populations of lymphoid cells, and was negative for all other antibodies. In the clonality test, lymphocyte co-expression of CD3 and CD20 was confirmed by monoclonal rearrangement of T-cell gamma receptors. The final diagnosis was type 2 enteropathy-associated T-cell lymphoma with hepatic infiltration. Co-expression was examined in conjunction with the PARR result in the presence of T-cell monoclonal rearrangement.

Satellite Noncoding RNAs (ncRNA) as Cancer Biomarkers? New Insights from FA-SAT ncRNA Molecular and Clinical Profiles in Feline Mammary Tumors.

Satellite noncoding RNAs (ncRNAs) are a new frontier of cancer biology research and biomarkers. While the knowledge on ncRNAs in human cancers is still limited, studies in other species can be informative to guide future translational research and development for cancer molecular targets and diagnostics. In this context, FA-SAT is the major satellite DNA of the cat genome, which is also present in humans, being transcribed in both species. In this study, we report new insights on FA-SAT (DNA and RNA) profile in feline mammary tumors, using disease-free tissues from the same animals as reference. We quantified the FA-SAT DNA and RNA levels (long and small transcripts) by real-time quantitative polymerase chain reaction (qPCR) and RT-qPCR. The comparison of the FA-SAT DNA and RNA levels with clinicopathological parameters revealed several associations, such as (1) the FA-SAT DNA levels' positive relation with lymphovascular invasion, (2) the FA-SAT long RNA negative correlation with Ki-67 index, and its positive association with Estrogen Receptor status, and (3) the FA-SAT small RNA level positive correlation with tumor size and skin ulceration. Also, FA-SAT long RNA is correlated with ERBB2 and c-MYC RNA levels. These data collectively suggest that FA-SAT ncRNA offers prospects as a potential cancer biomarker in cats. Further studies in humans are also needed to decipher the emerging role of ncRNAs in cancer biology and precision medicine fields. This work brings new information on the relation of FA-SAT ncRNAs with the oncogenic process, uncovering a new potential cancer biomarker.

Perioperative and oncological outcomes of laparoscopic and open radical nephroureterectomy for locally advanced upper tract urothelial carcinoma: a single-center cohort study.

Introduction: Open radical nephroureterectomy (ONU) is the standard of care for treatment of upper tract urothelial carcinoma (UTUC), but laparoscopic radical nephroureterectomy (LNU) is increasingly being used due to better perioperative outcomes. However, its oncological safety remains controversial, in particular for advanced disease.We aimed to compare perioperative and oncological outcomes between surgical approaches in locally advanced UTUC (≥pT3 and/or pN+). Material and methods: This study was a retrospective analysis of all 48 patients submitted to radical nephroureterectomy for advanced UTUC between 2006 and 2020 in our center.Perioperative data were compared between groups. Bladder tumor-free survival (BTFS), metastasis-free survival (MFS) and cancer-specific survival (CSS) were estimated using Kaplan-Meier curves and compared with log-rank p test. Multivariable Cox regression model was used to evaluate their association with surgical approach. Results: Clinical and pathological characteristics were similar between groups. LNU had lower blood loss (p = 0.031), need for transfusion (p = 0.013) and length of hospital stay (p <0.001), with similar operative time (p = 0.860).LNU was associated with better MFS (hazard ratio [HR]: 0.43, 95% confidence interval [CI] 0.20-0.93, p = 0.033) and CSS (HR: 0.42, 95%CI 0.19-0.94, p = 0.036). Median time to cancer death was 41 months for LNU and 12 months for ONU (log-rank p = 0.029). BTFS was similar between groups (HR: 0.60, 95%CI 0.17-2.11, p = 0.427). On multivariable Cox regression model, surgical approach wasn't significantly associated with MFS (p = 0.202), CSS (p = 0.149) or BTFS (p = 0.586). Conclusions: In our cohort of advanced UTUC, LNU did not result in inferior oncological control compared to ONU. The minimally invasive approach conferred an advantage in perioperative outcomes.

Effectiveness of Therapeutic Patient Education Interventions in Obesity and Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Diabetes mellitus (DM) and obesity account for the highest burden of non-communicable diseases. There is increasing evidence showing therapeutic patient education (TPE) as a clinically and cost-effective solution to improve biomedical and psychosocial outcomes among people with DM and obesity. The present systematic review and meta-analysis present a critical synthesis of the development of TPE interventions for DM and obesity and the efficacy of these interventions across a range of biomedical, psychosocial and psychological outcomes. A total of 54 of these RCTs were identified among patients with obesity and diabetes and were thus qualitatively synthesized. Out of these, 47 were included in the quantitative synthesis. There was substantial heterogeneity in the reporting of these outcomes (I2 = 88.35%, Q = 317.64), with a significant improvement noted in serum HbA1c levels (standardized mean difference (SMD) = 0.272, 95% CI: 0.118 to 0.525, n = 7360) and body weight (SMD = 0.526, 95% CI: 0.205 to 0.846, n = 1082) in the intervention group. The effect sizes were comparable across interventions delivered by different modes and delivery agents. These interventions can be delivered by allied health staff, doctors or electronically as self-help programs, with similar effectiveness (p < 0.001). These interventions should be implemented in healthcare and community settings to improve the health outcomes in patients suffering from obesity and DM.

The Landscape of Tumor-Infiltrating Immune Cells in Feline Mammary Carcinoma: Pathological and Clinical Implications.

Feline mammary carcinoma (FMC) shares key molecular and clinicopathological features with human breast cancer. We have herein studied the inflammatory infiltrate of FMC in order to uncover potential therapeutic targets and prognostic markers. To this end, the expression of different markers (CD3, CD4, CD8, CD20, CD56, FoxP3, CD68 and CD163) was analyzed in total, stromal (s) and intratumoral (i) tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs), in 73 feline mammary carcinomas. The results revealed that higher percentages of sCD8+ TILs were associated with longer disease-free survival (p = 0.05) and overall survival (p = 0.021). Additionally, higher percentages of iCD4+ TILs correlated with positive lymph node status (p = 0.003), whereas CD163+ TAMs were associated with undifferentiated tumors (p = 0.013). In addition, sCD3+ (p = 0.033), sCD8+ (p = 0.044) and sCD68+ (p = 0.023) immune cells were enriched in triple negative normal-like carcinomas compared to other subtypes. Altogether, our results suggest that specific subsets of immune cells may play a major role in clinical outcome of cats with mammary carcinoma, resembling what has been reported in human breast cancer. These data further support the relevance of the feline model in breast cancer studies.