[Diagnostic performance of biliopancreatic endosonography in patients with intermediate risk of choledocholithiasis]. / Rendimiento diagnóstico de la endosonografía biliopancreática en pacientes con riesgo intermedio de coledocolitiasis.

OBJECTIVE: Determine the sensitivity and specificity of the ESBP for diagnosis in patients with intermediate risk of choledocholithiasis, referred to the specialized surgical Gastroenterology center of Unión de Cirujanos SAS - Oncologists of the West Zentria group - Manizales - Colombia between March 01, 2020 to January 31, 2022. MATERIALS AND METHODS: Retrospective cross-sectional study in patients with intermediate risk for choledocholithiasis. The diagnostic performance of ESBP was calculated and confirmed with ERCP. Negative ESBPs were followed up by telephone. RESULTS: 752 cases with ESBP were analyzed, of which 43.2% (n=325) were positive and 56.8% (n=427) were negative. ERCP was performed in positive cases who accepted the procedure (n=317); 73.5% (n:233) were positive for choledocholithiasis, 25.8% (n=82) tumors and 0.6% (n=2) biliary roundworms. Patients with positive ESBP underwent ERCP. S= 98.3% (95% CI: 95.7-99.5) was obtained; E= 88.1% (95% CI: 79.2-94.1); PPV = 95.8% (95% CI: 92.4-98.0); NPV = 94.9% (95% CI: 87.4-98.7). The AUC of ESBP was 0.9319 (95% CI 0.8961-0.967). CONCLUSION: In patients with intermediate risk for choledocholithiasis, ESBP is a useful diagnostic option in the study of pancreatic pathologies, extrahepatic biliary tree, and the identification of biliary microlithiasis; Therefore, it also allows us to complement it with a therapeutic intervention such as ERCP in a single time.

Nuevas herramientas para la revisión de la medicación: PRM en pacientes en tratamiento con inhibidores de la bomba de protones / New tools for medication review: DRP in patients treatment with proton pump inhibitors

Objetivo Analizar mediante el programa de revisión de la medicación, Revisem®, la prevalencia de problemas relacionados con la medicación (PRM) en pacientes de la provincia de Valencia que estaban en tratamiento activo con inhibidores de la bomba de protones (IBP) en 2022. Diseño Estudio observacional descriptivo y retrospectivo. Material y métodos Se analizó el historial farmacoterapéutico (HFT) de 295 pacientes siguiendo los criterios propuestos por la Pharmaceutical Care Network Europe, utilizando la plataforma digital Revisem® del Muy Ilustre Colegio Oficial de Farmacéuticos de Valencia (MICOF). Resultados La edad media de los pacientes fue 81,8 ± 11,1 años y 66,4% fueron mujeres. Se detectó al menos un PRM en 97,3% de los pacientes. De los PRM analizados, 46,9% fueron interacciones, de las cuales 29,7% implicaban un IBP, siendo el omeprazol el de mayor frecuencia. Los PRM con IBP se relacionan de forma significativa con determinadas condiciones del paciente y grupos farmacológicos, como son el sexo femenino, la edad superior a 54 años y la polifarmacia. Conclusiones La plataforma digital Revisem®, permite la detección de una alta prevalencia de PRM a nivel provincial. La aplicación de nuevas herramientas tecnológicas para detectar la prevalencia de PRM es fundamental para optimizar los tratamientos de los pacientes. (AU)

Objective To analyze, using the medication review program, Revisem®, the prevalence of drug-related problems (DRP) in patients in the province of Valencia who were on active treatment with proton pump inhibitors (PPI) in 2022. Design Descriptive and retrospective observational study. Material and methods The pharmacotherapeutic history of 295 patients was analyzed following the criteria proposed by the Pharmaceutical Care Network Europe, using the Revisem® digital platform of the Muy Ilustre Colegio Oficial de Farmacéuticos (MICOF). Results The mean age of the patients was 81.8 ± 11.1 years and 66.4% were women. At least one DRP was detected in 97.3% of patients. 46.9% of the DRP analyzed were interactions, of which 29.7% involved a PPI, with omeprazole being the most frequent. DRPs with PPI are significantly related to certain patient conditions and pharmacological groups, such as female sex, age over 54 years and polypharmacy. Conclusions The application of the Revisem® digital platform allows the detection of a high prevalence of DRP at the provincial level. The application of new technological tools to detect the prevalence of DRP is essential to optimize patient treatments. (AU)

[New tools for medication review: DRP in patients treatment with proton pump inhibitors]. / Nuevas herramientas para la revisión de la medicación: PRM en pacientes en tratamiento con inhibidores de la bomba de protones.

OBJECTIVE: To analyze, using the medication review program, Revisem®, the prevalence of drug-related problems (DRP) in patients in the province of Valencia who were on active treatment with proton pump inhibitors (PPI) in 2022. DESIGN: Descriptive and retrospective observational study. MATERIAL AND METHODS: The pharmacotherapeutic history of 295 patients was analyzed following the criteria proposed by the Pharmaceutical Care Network Europe, using the Revisem® digital platform of the Muy Ilustre Colegio Oficial de Farmacéuticos (MICOF). RESULTS: The mean age of the patients was 81.8 ± 11.1 years and 66.4% were women. At least one DRP was detected in 97.3% of patients. 46.9% of the DRP analyzed were interactions, of which 29.7% involved a PPI, with omeprazole being the most frequent. DRPs with PPI are significantly related to certain patient conditions and pharmacological groups, such as female sex, age over 54 years and polypharmacy. CONCLUSIONS: The application of the Revisem® digital platform allows the detection of a high prevalence of DRP at the provincial level. The application of new technological tools to detect the prevalence of DRP is essential to optimize patient treatments.

Automatic processes moderate the association between reflective processes and movement behavior: A cross-sectional study.

Dual-process theories postulate that both reflective and automatic processes regulate health behavior. Further research is required to test the basic postulates of dual-process theories. We investigated the direct associations and moderating effect between automatic processes and multiple indicators of reflective processes on various levels of physical activity and sedentary behavior assessed using accelerometry in adults who were not participating in regular physical exercise programs. This cross-sectional study included 257 adults. Each participant completed a computerized test for automatic associations, a set of questions assessing reflective processes, a seven-day assessment using accelerometers to determine their levels of physical activity and sedentary behavior. The results showed a direct relationship between perceived benefits (B = 15.90, p = 0.043), perceived cons (B = -12.81, p = 0.034), decisional intention (B = -0.07, p = 0.049) with light physical activity, and self-efficacy with daily steps (B = 485.71, p = 0.008). There was a positive association between intention strength and daily steps when implicit associations favored physical activity (b = 623.36, LLCI = 79.09, ULCI = 1167.62, p = 0.025); a negative association between self-efficacy and sedentary behavior when implicit associations favored sedentary behavior (b = -25.73, LLCI = -49.77, ULCI = -1.70, p = 0.035); and a positive association between intention strength and sedentary behavior when implicit associations favored physical activity (b = 34.18, LLCI = 8.81, ULCI = 59.56, p = 0.008). These findings underscore the importance of considering the interplay between reflective and automatic processes in shaping movement behavior.

Metabolomic analysis reveals stress tolerance mechanisms in common bean (Phaseolus vulgaris L.) related to treatment with a biostimulant obtained from Corynebacterium glutamicum.

Microbial biostimulants have emerged as a sustainable alternative to increase the productivity and quality of important crops. Despite this, the effects of the treatment on plant metabolism are poorly understood. Thus, this study investigated the metabolic response of common bean (Phaseolus vulgaris) related to the treatment with a biostimulant obtained from the extract of Corynebacterium glutamicum that showed positive effects on the development, growth, and yield of crops previously. By untargeted metabolomic analysis using UHPLC-MS/MS, plants and seeds were subjected to treatment with the biostimulant. Under ideal growth conditions, the plants treated exhibited higher concentration levels of glutamic acid, nicotiflorin and glycosylated lipids derived from linolenic acid. The foliar application of the biostimulant under water stress conditions increased the chlorophyll content by 17% and induced the accumulation of flavonols, mainly quercetin derivatives. Also, germination seed assays exhibited longer radicle lengths for seeds treated compared to the untreated control even in the absence of light (13-18% increase, p-value <0.05). Metabolomic analysis of the seeds indicated changes in concentration levels of amino acids (tryptophan, phenylalanine, tyrosine, glutamine, and arginine) and their derivatives. The results point out the enhancement of abiotic stress tolerance and the metabolic processes triggered in this crop associated with the treatment with the biostimulant, giving the first insights into stress tolerance mechanisms in P. vulgaris.

Whole-exome sequencing of oral epithelial dysplasia samples reveals an association with new genes.

The genetic basis of oral epithelial (OED) is unknown, and there is no reliable method for evaluating the risk of malignant transformation. Somatic mutations are responsible for the transformation of dysplastic mucosa to invasive cancer. In addition, these genomic variations could represent objective markers of the potential for malignant transformation. We performed whole-exome sequencing of 10 OED samples from Brazilian and Chilean patients. Using public genetic repositories, we identified 41 deleterious variants that could produce high-impact changes in the amino acid structures of 38 genes. In addition, the variants were filtered according to normal skin and Native American genome profiles. Finally, 13 genes harboring 15 variants were found to be exclusively related to OED. High-grade epithelial dysplasia samples showed a tendency to accumulate highly deleterious variants. We observed that 62% of 13 OED genes identified in our study were also found in head and neck squamous cell carcinoma. Among the shared genes, eight were not identified in oral squamous cell carcinoma. To our knowledge, we have described for the first time 13 genes that are found in OED in a Latin American population, of which five genes have already been observed in oral squamous cell carcinoma. Through this study, we identified genes that may be related to basal biological functions in OED.

SARS-CoV-2 infection in patients with melanoma: results of the Spanish Melanoma Group registry.

BACKGROUND: The Spanish Melanoma Group (GEM) developed a national registry of patients with melanoma infected by SARS-CoV-2 ("GRAVID"). METHODS: The main objective was to describe the COVID-19 fatality rate in patients with melanoma throughout the pandemic, as well as to explore the effect of melanoma treatment and tumor stage on the risk of COVID-19 complications. These are the final data of the register, including cases from February 2020 to September 2021. RESULTS: One hundred-fifty cases were registered. Median age was 68 years (range 6-95), 61 (40%) patients were females, and 63 (42%) patients had stage IV. Thirty-nine (26%) were on treatment with immunotherapy, and 17 (11%) with BRAF-MEK inhibitors. COVID-19 was resolved in 119 cases, including 85 (57%) patients cured, 15 (10%) that died due to melanoma, and 20 (13%) that died due to COVID-19. Only age over 60 years, cardiovascular disorders, and diabetes mellitus increased the risk of death due to COVID-19, but not advanced melanoma stage nor melanoma systemic therapies. Three waves have been covered by the register: February-May 2020, August-November 2020, and December 2020-April 2021. The first wave had the highest number of registered cases and COVID-19 mortality. CONCLUSION: Tumor stage or melanoma treatments are non-significant prognostic factors for COVID-19 mortality. During the pandemic in Spain there was a downward trend in the number of patients registered across the waves, as well as in the severity of the infection. GOV IDENTIFIER: NCT04344002.

Whole-exome sequencing of oral epithelial dysplasia samples reveals an association with new genes

Abstract The genetic basis of oral epithelial (OED) is unknown, and there is no reliable method for evaluating the risk of malignant transformation. Somatic mutations are responsible for the transformation of dysplastic mucosa to invasive cancer. In addition, these genomic variations could represent objective markers of the potential for malignant transformation. We performed whole-exome sequencing of 10 OED samples from Brazilian and Chilean patients. Using public genetic repositories, we identified 41 deleterious variants that could produce high-impact changes in the amino acid structures of 38 genes. In addition, the variants were filtered according to normal skin and Native American genome profiles. Finally, 13 genes harboring 15 variants were found to be exclusively related to OED. High-grade epithelial dysplasia samples showed a tendency to accumulate highly deleterious variants. We observed that 62% of 13 OED genes identified in our study were also found in head and neck squamous cell carcinoma. Among the shared genes, eight were not identified in oral squamous cell carcinoma. To our knowledge, we have described for the first time 13 genes that are found in OED in a Latin American population, of which five genes have already been observed in oral squamous cell carcinoma. Through this study, we identified genes that may be related to basal biological functions in OED.

Use of stem cell-enriched fat grafts in facial reconstruction: have they demonstrated superiority over autologous fat grafting? / Uso de injertos de grasa enriquecidos con células madre en la reconstrución facial: ¿han demostrado superioridad sobre los injertos de grasa autólogos?

Since the 1990s, big strides have been made in plastic and reconstructive surgery, thanks to the implementation of new techniques and resources for its execution. In cases where restoration is sought for small defects, biosurgery, involving the utilization of stem cells, biomaterials, chemical engineering, and tissue engineering, can be employed. The potential to stimulate the innate regenerative capacity of tissue and generate a persistent response over time, minimizing surgical trauma and re-interventions, lies in stem cell transplantation. However, the evidence published on this matter is very scarce, leading to divergence of opinions, suggestions, and recommendations. The aim of this review is to analyze the most recent evidence concerning the outcomes of using fat grafts enriched with stem cells in facial reconstruction, as compared to autologous fat grafts. The review of the literature demonstrates a marked trend suggesting that fat grafts enriched with stem cells may be superior to autologous grafts in facial reconstruction, with potential benefits in medium-term volume retention and faster attainment of results. (AU)

La cirugía plástica y reconstructiva, ha dado pasos agigantados desde la década de los años 90, con la implementación de nuevas técnicas y recursos para su realización. En los casos de defectos pequeños donde se busca la restauración, se puede hacer uso de la biocirugía, que involucra el uso de células madre, biomateriales, ingeniería química y de tejidos. El trasplante de células madre, tiene el potencial de estimular la capacidad innata regenerativa del tejido, así como de generar una respuesta persistente a lo largo del tiempo, minimizando el trauma quirúrgico y la reintervención. A pesar, de la ventaja plausible, la calidad y cantidad de la evidencia publicada al respecto es muy escasa, ocasionando divergencia de opiniones, sugerencias y recomendaciones. Con base en lo anterior, el objetivo de esta revisión consiste en realizar un análisis de la evidencia más reciente sobre los resultados en el uso de injertos de grasa enriquecidos con células madre en la reconstrucción facial, comparado a los injertos de grasa autólogos. A través de la revisión de la literatura, se pudo evidenciar que, aunque la evidencia es heterogénea a la fecha, existe una tendencia marcada en que el uso de injertos de grasa enriquecidos con células madre, podría ser superior a los injertos autólogos en la reconstrucción facial, con potenciales beneficios en la retención de volumen a mediano plazo y mayor celeridad en la obtención de resultados. (AU)

Prevalence of Mild Cognitive Impairment in Southern Regions of Colombia.

Background: Recent reports suggest that by 2050 there will be an increase of around 310% of cases affected by dementia in Latin American countries. A previous study in a Southern region reported one of the highest prevalences of dementia in Latin America. Objective: To investigate the prevalence of mild cognitive impairment associated with low education, rurality, and demographic characteristics. Methods: A cross-sectional study recruited a community-dwelling sample of 823 adults from rural and urban areas of two Southern provinces of Colombia from 2020-2022. Participants were assessed with a neuropsychological protocol validated in Colombia. To obtain general and region-specific prevalence rates, age, sex, schooling, and socioeconomic level were considered and controlled for. Results: Most of the participants reported low education and socioeconomic level, the participation of women was higher. It was determined that the prevalence of mild cognitive impairment (MCI) was 53.6%, with 56.6% in the province of Caquetá followed by 51.9% in the province of Huila. The amnestic MCI represented 42.6%, the amnestic multi-domain was 39%, the non-amnestic 16.55%, and the non-amnestic multi-domain 1.81%. Our participants reported comorbidities such as diabetes and hypertension. We also observed a relationship between exposure to pesticides and MCI. Conclusions: We observed one of the highest prevalences of MCI in Latin America reported to date. Variables such as age, gender, and education proved risk factors for MCI in the explored regions. Our findings are very much in line with recent studies that highlight the influence of non-canonical risk factors of dementia in underrepresented countries from Latin America.

Daily step volume and intensity moderate the association of sedentary time and cardiometabolic disease risk in community-dwelling older adults: A cross-sectional study.

OBJECTIVE: To investigate the moderating effect of step count and peak cadence on the relationship of sedentary time and cardiometabolic disease risk in community-dwelling older adults. METHODS: This cross-sectional study included 248 older adults aged 60-80 years without cardiovascular disease (66.0 ± 4.6 years of age; 78 % females). Sedentary time, step count and peak cadence were measured by a hip-worn accelerometer for seven days. Peak cadence was defined as the average of 30 min of the day (but not necessarily consecutive) with the highest cadence (steps per minute) for all valid days. Cardiometabolic disease risk was defined using a sex-specific continuous metabolic syndrome score (cMetS). Sedentary time was used as an explanatory variable for cMetS and step count and peak cadence as moderators. The analyses were adjusted for known cardiometabolic disease risk factors and accelerometer wear time. The Johnson-Neyman technique was used to specify the value of moderator variables at which the significant relationship between sedentary time and cMetS disappears. RESULTS: Both step count (ß = -0.186, P = 0.032) and peak cadence (ß = -0.003, P = 0.007) showed a moderating effect on the relationship of sedentary time and cMetS. The association of sedentary time and cMetS was not statistically significant (p > 0.05) when step count or peak cadence exceed 5715 steps per day and 57 steps per minute, respectively. CONCLUSION: Steps per day and peak cadence moderate the association of sedentary time and cardiometabolic disease risk in older adults. Therefore, steps per day and peak cadence seem to offset the deleterious effects of sedentary time on cardiometabolic health in this population.

Pre-Frailty Phenotype and Arterial Stiffness in Older Adults Free of Cardiovascular Diseases.

PURPOSE: Arterial stiffness is a subclinical marker of cardiovascular disease (CVD). The pre-frailty phenotype is associated with a higher risk for CVD. This study investigated the association between the pre-frailty phenotype and arterial stiffness in community-dwelling older adults without diagnosed CVD. METHODS: In total, 249 community-dwelling older adults aged 60-80 years were included in this cross-sectional study. The pre-frailty phenotype was defined by the standardized Fried criteria (muscle weakness; slow walking speed; low physical activity; unintentional weight loss; self-reported exhaustion). Participants with one or two standardized Fried criteria were classified as pre-frail and those with zero criteria as robust. Arterial stiffness was measured by aortic pulse wave velocity (aPWV). The data were analyzed using the generalized linear model. RESULTS: From 249 participants (66.1 ± 5.3 years; 79.5% females), 61.8% (n = 154) were pre-frail and 38.2% (n = 95) robust. Pre-frail older adults had a higher aPWV (ß = 0.19 m/s; p = 0.007) compared to their robust peers. CONCLUSIONS: The pre-frailty phenotype was associated with higher arterial stiffness in community-dwelling older adults aged 60-80 years. Pre-frail older adults may have a higher risk for CVD.

Joint associations of accelerometer-measured physical activity and sedentary time with cardiometabolic risk in older adults: A cross-sectional study.

To investigate the joint associations of accelerometer-measured moderate-vigorous physical activity (MVPA) and sedentary time (ST) with cardiometabolic risk in older adults. This cross-sectional study included 248 participants (aged 65.8 ± 5.1 years; 73.7% females). Cardiometabolic risk was defined using continuous metabolic syndrome score (cMetS). MVPA and ST were assessed by accelerometry. Participants were categorized according to their MVPA and ST levels: i) 'Inactive + High ST' (<150 min/week and > 10.6 h/day); ii) 'Inactive + Low ST' (< 150 min/week and ≤ 10.6 h/day); iii) 'Active + High ST' (≥ 150 min/week and > 10.6 h/day) and iv) 'Active + Low ST' (≥ 150 min/week and ≤ 10.6 h/day). The cut-offs for active and inactive were based on current PA guidelines. The cut-offs for low and high ST were based on the median value from this cohort. Generalized linear models were used for data analyses ('Inactive + High ST' as group reference) controlling for known cardiometabolic risk factors. The 'Active + Low ST' (ß = -0.34, 95% CI -0.57, -0.11) and 'Active + High ST' (ß = -0.28, 95% CI -0.55, -0.02) groups had lower cMetS compared to the 'Inactive + High ST' group (p < 0.05). No difference was found between the 'Inactive + Low ST' and 'Inactive + High ST' groups (ß = -0.19, 95% CI -0.41, 0.03). Meeting MVPA recommendations (≥ 150 min/week) is associated with a lower cardiometabolic risk in older adults, even in those with high ST.

An Overview of Psychological Interventions on Breast Cancer Patients: Systematic Review of Randomized Controlled Trials

Introduction: Psychological morbidities are common in breast cancer patients. Clinical conditions like depression, cognitive alterations, anxiety, distress, fear of cancer, sleep disorders, and fatigue may persist in cancer survivors. Therefore, psychological interventions are an essential treatment for breast cancer. Objective: To identify psychological interventions and psychological outcomes for women with breast cancer. Methods: Five databases were searched: EMBASE, ScienceDirect, MEDLINE (Ovid), CENTRAL (Ovid) y PsycINFO (APA PsyNET), from Jan 2014 to Jun 4th, 2018. Two authors reviewed all title articles and abstracts in databases and selected potentially eligible studies. A narrative synthesis of results was used due to the heterogeneity in randomized controlled trials, population characteristics, psychotherapies applied, outcomes, and timing of assessments. Results: This overview included 14 randomized controlled trials which comprise 1914 participants (included non-metastatic and metastatic), across 21 articles. The most common psychological interventions were cognitive-behavioral based. The principal psychological outcomes assessed were depression, quality of life, fatigue, and anxiety. Conclusion: Results from this review are useful to clarify an overview of intervention in psychological morbidities in breast cancer. Comorbidities vary, contribute costs to patients, and there is insufficient empirical evidence about psychotherapies to resolve all psychological morbidities in breast cancer patients.

Introducción: Las morbilidades psicológicas son comunes en pacientes con cáncer de mama. Condiciones clínicas como depresión, alteraciones cognitivas, ansiedad, angustia, miedo al cáncer, trastornos del sueño y fatiga pueden persistir en sobrevivientes de cáncer. Por ello, las intervenciones psicológicas son relevantes durante el tratamiento en el cáncer de mama. Objetivo: Identificar intervenciones y resultados psicológicos para mujeres con cáncer de mama. Métodos: Se buscaron en cinco bases de datos: EMBASE, ScienceDirect, MEDLINE (Ovid), CENTRAL (Ovid) y PsycINFO (APA PsyNET), de enero de 2014 al 4 de junio de 2018. Dos autores revisaron todos los artículos en bases de datos y seleccionaron estudios potencialmente elegibles. Se utilizó una síntesis narrativa de los resultados debido a la heterogeneidad en ensayos controlados aleatorios, características de la población, psicoterapias aplicadas, resultados y tiempo de las evaluaciones. Resultados: Este resumen incluyó 14 ensayos controlados aleatorios que comprometen a 1914 participantes (incluidos no metastásicos y metastásicos) en 21 artículos. Las intervenciones psicológicas más comunes fueron basadas en el comportamiento cognitivo. Los principales resultados psicológicos evaluados fueron la depresión, la calidad de vida, la fatiga y la ansiedad. Conclusión: Los resultados de esta revisión son útiles para aclarar una visión general de la intervención en morbilidades psicológicas en el cáncer de mama. Las comorbilidades varían, contribuyen con costos a los pacientes y no hay suficiente evidencia empírica sobre psicoterapias para resolver todas las morbilidades psicológicas en la mujer con cáncer de mama.

Listeria delivers tetanus toxoid protein to pancreatic tumors and induces cancer cell death in mice.

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease. Tumors are poorly immunogenic and immunosuppressive, preventing T cell activation in the tumor microenvironment. Here, we present a microbial-based immunotherapeutic treatment for selective delivery of an immunogenic tetanus toxoid protein (TT856-1313) into PDAC tumor cells by attenuated Listeria monocytogenes. This treatment reactivated preexisting TT-specific memory T cells to kill infected tumor cells in mice. Treatment of KrasG12D,p53R172H, Pdx1-Cre (KPC) mice with Listeria-TT resulted in TT accumulation inside tumor cells, attraction of TT-specific memory CD4 T cells to the tumor microenvironment, and production of perforin and granzyme B in tumors. Low doses of gemcitabine (GEM) increased immune effects of Listeria-TT, turning immunologically cold into hot tumors in mice. In vivo depletion of T cells from Listeria-TT + GEM-treated mice demonstrated a CD4 T cell-mediated reduction in tumor burden. CD4 T cells from TT-vaccinated mice were able to kill TT-expressing Panc-02 tumor cells in vitro. In addition, peritumoral lymph node-like structures were observed in close contact with pancreatic tumors in KPC mice treated with Listeria-TT or Listeria-TT + GEM. These structures displayed CD4 and CD8 T cells producing perforin and granzyme B. Whereas CD4 T cells efficiently infiltrated the KPC tumors, CD8 T cells did not. Listeria-TT + GEM treatment of KPC mice with advanced PDAC reduced tumor burden by 80% and metastases by 87% after treatment and increased survival by 40% compared to nontreated mice. These results suggest that Listeria-delivered recall antigens could be an alternative to neoantigen-mediated cancer immunotherapy.

Consensus on prevention and treatment of cancer-associated thrombosis (CAT) in controversial clinical situations with low levels of evidence.

BACKGROUND: Cancer patients suffer high risk of venous thromboembolism (VTE). Cancer-associated VTE (CAT) causes hospitalization, morbidity, delayed cancer treatment, and mortality; therefore, exceptional CAT prevention and management are imperative. METHODS: This review offers practical recommendations and treatment algorithms for eight complex, clinically relevant situations posing great uncertainty regarding management and requiring an urgent decision: VTE prophylaxis in ambulatory cancer patients with pancreatic pancreas (1) or lung cancer with molecular alterations (2); optimal management of VTE during antineoplastic treatment with antiangiogenics (3) or chemotherapy (4); protracted VTE treatment, determinants; (5) drugs used (6), and optimal VTE management in situations of high bleeding risk (7) or recurrent VTE (8). RESULTS: With the evidence available, primary thromboprophylaxis in patients with lung cancer harbouring ALK/ROS1 translocations or pancreatic cancer receiving ambulatory chemotherapy must be appraised. If antiangiogenic therapy can yield a clear benefit and the patient recovers from a grade 3 thrombotic event, it can be cautiously re-introduced in selected cases, provided that the person agrees to assume the risk after being duly informed. Anticoagulation maintenance beyond 6 months is recommended in individuals with metastatic tumours, on active treatment, or at high risk for recurrent VTE without bleeding risk. In such cases, LMWH and DOACs are safe, being mindful that the latter could entail a higher risk of bleeding; consequently, they should be used judiciously in more haemorrhagic tumours, such as gastrointestinal cancers. In cases of recurrent VTE, the presence of active cancer, infra-therapeutic dose, and anticoagulant treatment failure must be ruled out. In individuals with platelet counts of 25,000-50,000 and VTE liable to recur who need anticoagulation, full-dose LMWH and transfusion support can be contemplated to reach values of > 50,000. In CAT unlikely to recur, decreasing the LMWH dose by 25-50% is recommended. Renal impairment associated with thrombosis must be treated with LMWHs; there is no need to adjust the dose in patients with CrCl > 30; with CrCl = 15-30, dose adjustment is advised, and suspended when CrCl is < 15. CONCLUSION: We provide useful advice for complex, clinically relevant situations that clinicians treating CAT must face devoid of any unequivocal, strong, evidence-based recommendations.

Macrophages Modulate Hepatic Injury Involving NLRP3 Inflammasome: The Example of Efavirenz.

Drug-induced liver injury (DILI) constitutes a clinical challenge due to the incomplete characterization of the mechanisms involved and potential risk factors. Efavirenz, an anti-HIV drug, induces deleterious actions in hepatocytes that could underlie induction of the NLRP3 inflammasome, an important regulator of inflammatory responses during liver injury. We assessed the potential of efavirenz to modulate the inflammatory and fibrogenic responses of major liver cell types involved in DILI. The effects of efavirenz were evaluated both in vitro and in vivo. Efavirenz triggered inflammation in hepatocytes, in a process that involved NF-κB and the NLRP3 inflammasome, and activated hepatic stellate cells (HSCs), thereby enhancing expression of inflammatory and fibrogenic markers. The NLRP3 inflammasome was not altered in efavirenz-treated macrophages, but these cells polarized towards the anti-inflammatory M2 phenotype and displayed upregulated anti-inflammatory mediators. Conversely, no evidence of damage was observed in efavirenz-treated animals, except when macrophages were depleted, which resulted in the in vivo manifestation of the deleterious effects detected in hepatocytes and HSCs. Efavirenz elicits a cell-specific activation of the NLRP3 inflammasome in hepatocytes and HSCs, but macrophages appear to counteract efavirenz-induced liver injury. Our results highlight the dynamic nature of the interaction among liver cell populations and emphasize the potential of targeting macrophage polarization as a strategy to treat NLRP3 inflammasome-induced liver injury.

Clinicopathological predictors of survival in resected primary lung adenocarcinoma.

AIMS: Primary lung adenocarcinoma consists of a spectrum of clinical and pathological subtypes that may impact on overall survival (OS). Our study aims to evaluate the impact of adenocarcinoma subtype and intra-alveolar spread on survival after anatomical lung resection and identify different prognostic factors based on stage and histological subtype. METHODS: Newly diagnosed patients undergoing anatomical lung resections without induction therapy, for pT1-3, N0-2 lung adenocarcinoma from April 2011 to March 2013, were included. The effect of clinical-pathological factors on survival was retrospectively assessed. RESULTS: Two hundred and sixty-two patients were enrolled. The 1-year, 3-year and 5-year OS were 88.8%, 64.3% and 51.1%, respectively. Univariate analysis showed lymphovascular, parietal pleural and chest wall invasion to confer a worse 1-year and 5-year prognosis (all p<0.0001). Solid predominant adenocarcinomas exhibited a significantly worse OS (p=0.014). Multivariate analysis did not identify solid subtype as an independent prognostic factor; however, identified stage >IIa, lymphovascular invasion (p=0.002) and intra-alveolar spread (p=0.009) as significant independent predictors of worse OS. Co-presence of intra-alveolar spread and solid predominance significantly reduced OS. Disease-free survival (DFS) was reduced with parietal pleural (p=0.0007) and chest wall invasion (p<0.0001), however, adenocarcinoma subtype had no significant impact on DFS. CONCLUSIONS: Our study demonstrates that solid predominant adenocarcinoma, intra-alveolar spread and lymphovascular invasion confer a worse prognosis and should be used as a prognostic tool to determine appropriate adjuvant treatment.

Neurological Manifestations and Outcomes in a Retrospective Cohort of Mexican Inpatients with SARS-CoV-2 Pneumonia: Design of a Risk Profile.

We analyzed the neurological manifestations in Mexican patients hospitalized with pneumonia due to COVID-19 and investigated the association between demographic, clinical, and biochemical variables and outcomes, including death. A retrospective, analytical study was conducted using the electronic records of patients hospitalized between 1 April 2020 and 30 September 2020. Records of 1040 patients were analyzed: 31.25% died and 79.42% had neurological symptoms, including headache (80.62%), anosmia (32.20%), ageusia (31.96%), myopathy (28.08%), disorientation (14.89%), encephalopathy (12.22%), neuropathy (5.4%), stroke (1.3%), seizures (1.3%), cerebral hemorrhage (1.08%), encephalitis (0.84%), central venous thrombosis (0.36%), and subarachnoid hemorrhage (0.24%). Patients also had comorbidities, such as hypertension (42.30%), diabetes mellitus (38.74%), obesity (61.34%), chronic obstructive pulmonary disease (3.17%), and asthma (2.01%). Factors associated with neurological symptoms were dyspnea, chronic obstructive pulmonary disease, advanced respiratory support, prolonged hospitalization, and worsening fibrinogen levels. Factors associated with death were older age, advanced respiratory support, amine management, chronic obstructive pulmonary disease, intensive care unit management, dyspnea, disorientation, encephalopathy, hypertension, neuropathy, diabetes, male sex, three or more neurological symptoms, and obesity grade 3. In this study we designed a profile to help predict patients at higher risk of developing neurological complications and death following COVID-19 infection.

BRAFV600E Mutant Allele Frequency (MAF) Influences Melanoma Clinicopathologic Characteristics.

BACKGROUND: Cutaneous melanoma shows high variability regarding clinicopathological presentation, evolution and prognosis. METHODS: Next generation sequencing was performed to analyze hotspot mutations in different areas of primary melanomas (MMp) and their paired metastases. Clinicopathological features were evaluated depending on the degree of variation of the BRAFV600E mutant allele frequency (MAF) in MMp. RESULTS: In our cohort of 14 superficial spreading, 10 nodular melanomas and 52 metastases, 17/24 (71%) melanomas had a BRAFV600E mutation and 5/24 (21%) had a NRASQ61 mutation. We observed a high variation of BRAFV600E MAF (H-BRAFV600E) in 7/17 (41%) MMp. The H-BRAFV600E MMp were all located on the trunk, had lower Breslow and mitotic indexes and predominantly, a first nodal metastasis. Regions with spindled tumor cells (Spin) and high lymphocytic infiltrate (HInf) were more frequent in the H-BRAFV600E patients (4/7; 57%), whereas regions with epithelial tumor cells (Epit) and low lymphocytic infiltrate (LInf) were predominant (6/10; 60%) and exclusive in the low BRAFV600E MAF variation tumors (L-BRAFV600E). The H-BRAFV600E/Spin/HInf MMp patients had better prognostic features and nodal first metastasis. CONCLUSIONS: The H-BRAFV600E MMp were located on the trunk, had better prognostic characteristics, such as lower Breslow and mitotic indexes as well as high lymphocytic infiltrate.