Outcomes with atezolizumab in metastatic urothelial cancer: real-world data from a single institution

Purpose Immune checkpoint inhibitors (ICIs) have been incorporated in the treatment of metastatic urothelial carcinoma (mUC) upon platinum-based chemotherapy according to the positive results of large clinical trials. Nevertheless, results from unselected populations reflecting real-world data (RWD) are highly informative to the clinician. We reviewed daily clinical practice outcomes in patients with mUC who received atezolizumab in our institution. Methods Here we evaluated the clinical activity and safety of atezolizumab in an unselected population of mUC patients who received atezolizumab between 2018 and 2022 reflecting RWD. Efficacy and safety information were retrospectively collected. Results A total of 63 patients were included. The mean age was 68 years and the objective response rate was 14.3%. The median progression-free survival was 3 months and the median overall survival 6 months. At 1 year, 42% of the patients were alive. ECOG (0 vs 1) and neutrophil–lymphocytes ratio < 2 at the start of ICI were positive prognostic factors that discriminated between long vs short survivors. Overall tolerance was good with no new safety signals. Five patients (17%) had treatment-related adverse events grade ≥ 2 that required corticosteroids. Conclusion In this retrospective study, atezolizumab was an effective and tolerable treatment option for patients with mUC after progression to platinum-based chemotherapy. Yet, patient selection remains critical to improve outcomes (AU)

Outcomes with atezolizumab in metastatic urothelial cancer: real-world data from a single institution.

PURPOSE: Immune checkpoint inhibitors (ICIs) have been incorporated in the treatment of metastatic urothelial carcinoma (mUC) upon platinum-based chemotherapy according to the positive results of large clinical trials. Nevertheless, results from unselected populations reflecting real-world data (RWD) are highly informative to the clinician. We reviewed daily clinical practice outcomes in patients with mUC who received atezolizumab in our institution. METHODS: Here we evaluated the clinical activity and safety of atezolizumab in an unselected population of mUC patients who received atezolizumab between 2018 and 2022 reflecting RWD. Efficacy and safety information were retrospectively collected. RESULTS: A total of 63 patients were included. The mean age was 68 years and the objective response rate was 14.3%. The median progression-free survival was 3 months and the median overall survival 6 months. At 1 year, 42% of the patients were alive. ECOG (0 vs 1) and neutrophil-lymphocytes ratio < 2 at the start of ICI were positive prognostic factors that discriminated between long vs short survivors. Overall tolerance was good with no new safety signals. Five patients (17%) had treatment-related adverse events grade ≥ 2 that required corticosteroids. CONCLUSION: In this retrospective study, atezolizumab was an effective and tolerable treatment option for patients with mUC after progression to platinum-based chemotherapy. Yet, patient selection remains critical to improve outcomes.

Repeated loss of the ability of a wild pepper disease resistance gene to function at high temperatures suggests that thermoresistance is a costly trait.

Specificity in plant-pathogen gene-for-gene (GFG) interactions is determined by the recognition of pathogen proteins by the products of plant resistance (R) genes. The evolutionary dynamics of R genes in plant-virus systems is poorly understood. We analyse the evolution of the L resistance locus to tobamoviruses in the wild pepper Capsicum annuum var. glabriusculum (chiltepin), a crop relative undergoing incipient domestication. The frequency, and the genetic and phenotypic diversity, of the L locus was analysed in 41 chiltepin populations under different levels of human management over its distribution range in Mexico. The frequency of resistance was lower in Cultivated than in Wild populations. L-locus genetic diversity showed a strong spatial structure with no isolation-by-distance pattern, suggesting environment-specific selection, possibly associated with infection by the highly virulent tobamoviruses found in the surveyed regions. L alleles differed in recognition specificity and in the expression of resistance at different temperatures, broad-spectrum recognition of P0 + P1 pathotypes and expression above 32°C being ancestral traits that were repeatedly lost along L-locus evolution. Overall, loss of resistance co-occurs with incipient domestication and broad-spectrum resistance expressed at high temperatures has apparent fitness costs. These findings contribute to understand the role of fitness trade-offs in plant-virus coevolution.

Non-antibiotic treatment of uncomplicated acute diverticulitis is applicable and safe in our environment. A prospective multicenter study.

INTRODUCTION: acute diverticulitis is one of the most frequent underlying causes behind individuals attending the Emergency Room with abdominal pain. The most widespread therapy for acute uncomplicated diverticulitis includes outpatient treatment with antibiotics; however, several publications indicate that patients can also be successfully treated without antibiotics. The results of the implementation of this more recent protocol in two hospitals in Madrid are presented. METHODS: an observational prospective study was performed. Participants were patients diagnosed with uncomplicated acute diverticulitis at two hospitals in Madrid, Hospital Universitario de Torrejón and Hospital Universitario Puerta de Hierro Majadahonda, between December 2018 and August 2021, treated on an outpatient basis without antibiotic therapy. The study group was compared with a control group, composed of patients diagnosed with uncomplicated acute diverticulitis and treated with outpatient antibiotic therapy at Hospital Universitario Puerta de Hierro between March 2015 and March 2018. RESULTS: three hundred and sixty-one patients were included, 182 in the study group and 179 in the control group. Diverticulitis was persistent in 19 patients (10.4 %) in the study group, who were not treated with antibiotics, and in five patients (2.8 %) in the control group, treated with outpatient antibiotic therapy (p = 0.004). Recurrences occurred in 23 patients (12.6 %) in the study group, and in 53 patients (29.6 %) in the control group (p < 0.0001). The analysis of the complications found no significant differences between both groups (p = 0.109). No urgent surgical intervention or mortality was recorded in the study group. CONCLUSIONS: in our environment, symptomatic non-antibiotic treatment of uncomplicated acute diverticulitis cases is safe, without showing a higher rate of complications. Although, there seems to be a worse initial symptom control.

Non-antibiotic treatment of uncomplicated acute diverticulitis is applicable and safe in our environment. A prospective multicenter study

Introduction: acute diverticulitis is one of the most frequent underlying causes behind individuals attending the Emergency Room with abdominal pain. The most widespread therapy for acute uncomplicated diverticulitis includes outpatient treatment with antibiotics; however, several publications indicate that patients can also be successfully treated without antibiotics. The results of the implementation of this more recent protocol in two hospitals in Madrid are presented. Methods: an observational prospective study was performed. Participants were patients diagnosed with uncomplicated acute diverticulitis at two hospitals in Madrid, Hospital Universitario de Torrejón and Hospital Universitario Puerta de Hierro Majadahonda, between December 2018 and August 2021, treated on an outpatient basis without antibiotic therapy. The study group was compared with a control group, composed of patients diagnosed with uncomplicated acute diverticulitis and treated with outpatient antibiotic therapy at Hospital Universitario Puerta de Hierro between March 2015 and March 2018. Results: three hundred and sixty-one patients were included, 182 in the study group and 179 in the control group. Diverticulitis was persistent in 19 patients (10.4 %) in the study group, who were not treated with antibiotics, and in five patients (2.8 %) in the control group, treated with outpatient antibiotic therapy (p = 0.004). Recurrences occurred in 23 patients (12.6 %) in the study group, and in 53 patients (29.6 %) in the control group (p < 0.0001). The analysis of the complications found no significant differences between both groups (p = 0.109). No urgent surgical intervention or mortality was recorded in the study group. Conclusions: in our environment, symptomatic non-antibiotic treatment of uncomplicated acute diverticulitis cases is safe, without showing a higher rate of complications. Although, there seems to be a worse initial symptom control. (AU)

Anomie, irritation, and happiness in the Chilean society post-social outbreak.

On 18 October 2019, the Chilean people witnessed an unprecedented social outbreak across most of their country. We argue that a state of anomie is a factor associated with the weakening of states, and an anomic state might negatively influence people's well-being through an increased feeling of irritation. Convenience recruitment via social networks allowed us to form a sample of 194 Chilean participants from the center-south region of the country (M = 36.53 years old, SD = 17.48; 56.7% women). All participants completed testing instruments to measure anomie, irritation, happiness, and political beliefs. Descriptive scores suggest situating Chile in the quadrant of high anomie. Two mediation analyses were conducted. The main results showed a negative indirect effect of the breakdown of the social fabric and leadership on happiness through irritation, although the findings for the former dimension were more robust. Additionally, the breakdown of the social fabric was positively related to the belief that left and right-wing democratic governments are helpless when it comes to fighting delinquency. The breakdown of leadership, on the other hand, was negatively related to political interest. The results should be interpreted with caution due to the limitations of the sample type and the construction validity of some instruments.

Primeras recomendaciones de consenso SLANH - COLABIOCLI / Primeiras Recomendações de Consenso SLANH - COLABIOCLI / (Sociedad Latinoamericana de Nefrología e Hipertensión - Confederación Latinoamericana de Bioquímica Clínica) / Informe de la tasa de filtración glomerular estimada junto a la determinación de la creatininemia en población adulta / First SLANH-COLABIOCLI Consensus Recommendations

Resumen La enfermedad renal crónica (ERC) es de alta prevalencia en América Latina y en todo el mundo. Se estima que entre 10 y 20% de la población adulta es portadora de ERC y su prevalencia va en aumento. La ERC progresa en forma silenciosa. Su diagnóstico temprano y oportuno permite iniciar un tratamiento efectivo, en la mayoría de los casos, para detener la enfermedad. Desde hace mucho tiempo, el análisis de la creatininemia es la principal prueba utilizada para valorar la función renal, pero su confiabilidad es limitada. De acuerdo con las recomendaciones de las GUIAS KDOQI del año 2002 la tasa de filtración glomerular estimada (TFGe) obtenida a través de fórmulas, se estableció como una de las herramientas principales para detectar la enfermedad renal de manera precoz, ya que alerta de forma precisa al médico y al equipo de salud sobre el nivel de función renal del paciente. La detección de una TFGe disminuida (menor de 60 mL/min/1,73 m2) es clínicamente relevante, ya que permite establecer el diagnóstico de enfermedad renal en adultos. En el año 2022, en una encuesta realizada por SLANH y COLABIOCLI dirigida a los laboratorios de análisis clínicos de América Latina (n: 237), el 49% de los mismos no informaban la TFGe rutinariamente. En base a esta realidad SLANH y COLABIOCLI elaboraron estas recomendaciones de consenso en referencia al uso de la TFGe.

Abstract Chronic kidney disease (CKD) has a high prevalence worldwide and in Latin America (10 to 20% of the adult population) and is increasing. CKD progresses silently. Opportune diagnosis and treatment are effective in most cases to improve outcomes. Serum creatinine was the main test to assess kidney function, but its reliability is limited. Through the KDOQI Guidelines 2002, the estimated glomerular filtration rate (eGFR) obtained from equations was established as one of the main tools for the early detection of kidney disease in clinical practice. The detection of a decreased eGFR (less than 60 mL/min/1.73 m2) is clinically relevant. This cut-off level establishes the diagnosis of kidney disease in adults. In 2022 SLANH and COLABIOCLI conducted a survey among the clinical laboratories from Latin America. The survey included 237 laboratories, 49% of which did not routinely report the eGFR. Based on this situation, SLANH and COLABIOCLI have elaborated the following consensus recommendations regarding the use of eGFR.

Resumo A doença renal crônica (DRC) é altamente prevalente na América Latina e em todo o mundo. Estima-se que entre 10 e 20% da população adulta seja portadora de DRC e sua prevalência esteja aumentando. A DRC progride silenciosamente. Seu diagnóstico precoce e oportuno permite iniciar um tratamento eficaz, na maioria dos casos, para estancar a doença. Faz muito tempo, a análise da creatinina tem sido o principal teste usado para avaliar a função renal mas sua confiabilidade é limitada. De acordo com as recomendações dos GUIAS KDOQI do ano de 2002, a estimativa da taxa de filtração glomerular (eGFR), obtida por meio de fórmulas, consolidou-se como uma das principais ferramentas para a detecção precoce da doença renal, visto que alerta com precisão ao médico e ao equipe de saúde sobre o nível de função renal do paciente. A detecção de uma eGFR diminuída (inferior a 60 mL/min/1,73 m2) é clinicamente relevante, pois permite estabelecer o diagnóstico de doença renal em adultos. No ano de 2022, em pesquisa realizada pela SLANH e COLABIOCLI dirigida a laboratórios de análises clínicas da América Latina (n: 237), 49% deles não relataram rotineiramente eGFR. Com base nessa realidade, SLANH e COLABIOCLI prepararam essas recomendações de consenso sobre o uso de eGFR.

Neoadjuvant immunotherapy for dMMR/MSI-H locally advanced rectal cancer: The future new standard approach?

INTRODUCTION: This is a review of the evidence from studies of the efficacy and tolerability of neoadjuvant immunotherapy for mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) Locally Advanced Rectal Cancer (LARC). METHODS: For this review, we searched EMBASE and MEDLINE until 22 September 2022. The terms used in the search included mismatch repair-deficient, microsatellite instability, rectal cancer, neoadjuvant and immunotherapy. RESULTS: A total of 92 studies were obtained but only 9 were selected for the final analysis (one prospective and eight retrospective studies), including less than 20 patients per study. Neoadjuvant immunotherapy provides overall response rates of 100% (with and completed clinical response between 40 and 100%). CONCLUSION: Our review discusses completed prospective and retrospective studies, ongoing clinical trials, and the clinical practice of using neoadjuvant immunotherapy for MSI-H/dMMR LARC. The promising results obtained, would open the door to exploring other alternatives for these patients, offering the possibility of avoiding chemoradiation therapy and surgery in the future.

El lado menos dulce de la diabetes. Revisión pictográfica de las alteraciones más frecuentes en el pie diabético / The not-so-sweet Side of Diabetes. Pictorial Review of the Most Frequent Diabetic Foot Disorders

Resumen La prevalencia global de diabetes mellitus (DM) aumenta cada año y, con ella, sus complicaciones. La afección del pie relacionada con DM se ha convertido en una de las principales causas de morbilidad y discapacidad. Los hallazgos más frecuentes son las alteraciones cutáneas y musculares, la arterioesclerosis y el edema óseo. Las complicaciones son la osteomielitis y la neuroartropatía, siendo causas importantes de amputación. El estudio imagenológico se inicia con radiografía (Rx), que permite descartar anomalías óseas y articulares, presencia de cuerpos extraños o alteraciones del tejido blando. Después de la Rx, la resonancia magnética (RM) es la modalidad de elección para la evaluación de la osteomielitis e infección de tejidos blandos del pie. Aunque esas afecciones comparten algunas características clínicas y de imagen con otros trastornos, el conocimiento de sus hallazgos distintivos permite al radiólogo contribuir al diagnóstico oportuno y correcto, con el fin de proporcionar al clínico información adecuada.

Abstract The global prevalence of Diabetes Mellitus (DM) tends to increase over the years, along with its complications. Diabetes related foot disease has become one of the leading causes of morbidity and disability. The most frequent findings are skin and muscle disorders, arteriosclerosis and bone marrow edema. Complications are osteomyelitis and neuroarthropathy, being important causes of amputation. The imaging study begins with radiography, which allows to rule out bone and joint abnormalities, presence of foreign bodies or soft tissue alterations. After radiography, magnetic resonance imaging (MRI) is the chosen modality to study osteomyelitis and soft tissue infection of the foot. Although these conditions share some clinical and imaging characteristics with other disorders, to know the distinctive findings allows the radiologist to contribute to get a timely and correct diagnosis, providing as well an appropriate information to the clinician.

Seasonality of Coxiella burnetii among Wild Rabbits (Oryctolagus cuniculus) and the Hyalomma lusitanicum (Acari: Ixodidae) in a Meso-Mediterranean Ecosystem.

(1) Background: Q fever is a worldwide zoonosis caused by Coxiella burnetii that have cases reported in humans and animals almost everywhere. The aim of this study was to describe the seasonality of Coxiella burnetii in the wild rabbit (Oryctolagus cuniculus) and the tick Hyalomma lusitanicum in a meso-Mediterranean ecosystem. (2) Methods: two populations of wild rabbits that differ in whether or not they share habitat with ungulates, mainly red deer (Cervus elaphus) were sampled for a year to collect ticks, blood and vaginal or anal swabs. Presence of C. burnetii DNA in swabs and the tick H. lusitanicum was determined by PCR and serum antibodies by ELISA. (3) Results: C. burnetii DNA was detected in 47.2% of 583 rabbits, in 65.5% of sera, and in more than half of the H. lusitanicum. There were small variations according to sex and age of the rabbits but significant according to the habitat (4) Conclusions: The results indicate that C. burnetii circulates freely between wild rabbits and H. lusitanicum and the sylvatic cycle in meso-Mediterranean environments relies in the presence of wild rabbits and H. lusitanicum above all if sharing habitat with red deer.

Biophilia and Biophobia as Emotional Attribution to Nature in Children of 5 Years Old.

INTRODUCTION: Connectedness to nature is a concept that reflects the emotional relationship between the self and the natural environment, based on the theory of biophilia, the innate predisposition to the natural environment. However, the biophobic component has largely been ignored, despite, given its adaptive functional role, being an essential part of the construct. If there is a phylogenetic component underlying nature connectedness, biophilic, and/or biophobic, there should be evidence of this record from early childhood. The main aim of this study is therefore to describe the emotional attributions identified in 5 years old. METHODOLOGY: Two studies were conducted. In the first, 94 children expressed their concept of nature and made basic emotional attributions to a set of 30 images of natural, using a software designed for the study. In the second, 39 children repeated the procedure and provided explanations for their responses. RESULTS: The main results show that, in general, children use both positive and negative emotions, which may be related to a three-dimensional model of emotional attributions to nature. The most widely attributed emotion is happiness. However, fear is the second most common attribution. The role of happiness could be explained by a feeling of security and familiarity, while the importance of fear in nature could show an adaptive response of the fear of wild nature in children. This interpretation could be confirmed when analyzing specifically the emotional attributions, classifying the images according to biological and ecosystemic criteria. Thus, for example, more emotional attributions are explained by the "pleasantness" attributed to primary producers and landscapes (e.g., flora), versus attributions of "harm" to the images of secondary and tertiary consumers (e.g., hunters). CONCLUSION: These results provide evidence in favor of a didactic procedure to study emotional attributions to images of nature in preschool children. They suggest the incorporation of biophobia as an important adaptive factor in connectedness to nature and a tripartite emotional hypothesis based on the valences of the attributed emotions.

Mandibular Fracture as First Sign of an Occult Intraosseous Hemangioma.

Intraosseous hemangioma (IH) in the maxillofacial area is a very uncommon neoplasm. Here, the authors show an exceptional case not previously reported in the literature of a 65-year-old man who presented with a pathological mandibular fracture following a facial trauma that was the first sign of an occult cavernous IH. Complete excision of the tumor in the mandibular ramus reduced the risk of severe bleeding and prevented long-term recurrence, whereas immobilization of the fracture obtained an excellent functional result. This clinical report highlights the possibility that a previously unknown primary IH may debut as a pathological fracture and the importance of differential diagnosis in this location.

Adenocarcinoma de colon pobremente diferenciado con diferenciación rabdoide: un diagnóstico anatomopatológico extremadamente infrecuente / Poorly differentiated colonic adenocarcinoma showing rhabdoid feature: An extremely unusual anatomopathological diagnosis

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Programming of Dopaminergic Neurons by Early Exposure to Sex Hormones: Effects on Morphine-Induced Accumbens Dopamine Release, Reward, and Locomotor Behavior in Male and Female Rats.

Neonatal programming with sex hormones produces long-term functional changes in various tissues, including the brain. Previously, we demonstrated a higher content of dopamine and an increase in potassium-induced dopamine release in the nucleus accumbens of adult rats exposed to estradiol valerate. On the other hand, sex hormones also affect the opioid system increasing the expression of the µ opioid receptor and ß-endorphins. Here, we investigated if neonatal programming with sex hormones alters the response to morphine during adulthood in rats and predispose them to neurochemical, rewarding and behavioral activating effects. We examined the effects of neonatal exposure to a single dose of estradiol valerate or testosterone propionate on morphine-induced (5 mg/kg, i.v.) dopamine release in the nucleus accumbens and morphine-induced (3 mg/kg, s.c.) locomotor activity and conditioned place preference when these rats were adults. Our results showed a significant increase in morphine-induced dopamine release in the nucleus accumbens of rats that were exposed neonatally to estradiol compared with control rats. This effect was correlated with higher place preference and locomotor activity induced by morphine in adult rats neonatally exposed to estradiol valerate. However, the effect of morphine on dopamine release and behaviors was similar in rats treated with testosterone compared to control rats. Additionally, the expression of mu (µ) opioid receptor, dopamine receptor type 1 (D1) and dopamine receptor type 2 (D2) in the nucleus accumbens of adult rats was not different after treatment with sex hormones. Taken together, our results demonstrated an enhancement of pharmacological effects produced by morphine in rats neonatally programmed with estradiol valerate, suggesting that early exposure to sex hormones could represent a vulnerability factor in the development of addiction to opioid drugs such as morphine and heroin in adulthood.

Picadura por araña Loxosceles en labio inferior / Loxosceles spider bite in lower lip

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Environmental heterogeneity and the evolution of plant-virus interactions: Viruses in wild pepper populations.

Understanding host-pathogen interactions requires analyses to address the multiplicity of scales in heterogeneous landscapes. Anthropogenic influence on plant communities, especially cultivation, is a major cause of environmental heterogeneity. We have approached the analysis of how environmental heterogeneity determines plant-virus interactions by studying virus infection in a wild plant currently undergoing incipient domestication, the wild pepper or chiltepin, across its geographical range in Mexico. We have shown previously that anthropogenic disturbance is associated with higher infection and disease risk, and with disrupted patterns of host and virus genetic spatial structure. We now show that anthropogenic factors, species richness, host genetic diversity and density in communities supporting chiltepin differentially affect infection risk according to the virus analysed. We also show that in addition to these factors, a broad range of abiotic and biotic variables meaningful to continental scales, have an important role on the risk of infection depending on the virus. Last, we show that natural virus infection of chiltepin plants in wild communities results in decreased survival and fecundity, hence negatively affecting fitness. This important finding paves the way for future studies on plant-virus co-evolution.

Optimization of the balance between effort and yield in unilateral surgical transfer of mouse embryos.

Surgical transfer of embryos is carried out daily in animal facilities worldwide for the rederivation of mouse strains/lines, among other purposes. Current protocols described in laboratory manuals recommend using a high number of embryos during transfer, typically in the range of 15 up to 25. To optimize the use of resources it is necessary to estimate and relate the effort required and the yield obtained. Here, we analyse the balance between the number of embryos transferred (the effort), and the yield as the number of born pups obtained from surgical embryo transfer. To accomplish this, we have analyzed data obtained during rederivation of nearly one hundred lines of mice to a new animal facility. Our results confirm that the use of increasing numbers of embryos per transfer increases the yields of born pups, as has been described previously in the literature, but they also highlight the disproportionate effort required, i.e. in the number of embryos that needed to be transferred. An estimate of the mean expected yields of surgical transfers and their comparison with the actual observed yields indicated that the balance between effort and yield is optimized when using lower numbers of embryos than in currently used protocols, in the range of 8 to 12. Given the heterogeneous nature of the data presented and analyzed here, which is from a population of mice that may be considered as representative of any animal facility, our optimization approach should help save resources in similar facilities and improve the yields of embryo transfer procedures.

¿Cuál es su diagnóstico? / What would your diagnosis be?

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