Biomarkers in Metastatic Colorectal Cancer: Status Quo and Future Perspective.

Colorectal cancer (CRC) is the third most frequent cancer worldwide, and its incidence is steadily increasing. During the last two decades, a tremendous improvement in outcome has been achieved, mainly due to the introduction of novel drugs, targeted treatment, immune checkpoint inhibitors (CPIs) and biomarker-driven patient selection. Moreover, progress in molecular diagnostics but also improvement in surgical techniques and local ablative treatments significantly contributed to this success. However, novel therapeutic approaches are needed to further improve outcome in patients diagnosed with metastatic CRC. Besides the established biomarkers for mCRC, such as microsatellite instability (MSI) or mismatch repair deficiency (dMMR), RAS/BRAF, sidedness and HER2 amplification, new biomarkers have to be identified to better select patients who derive the most benefit from a specific treatment. In this review, we provide an overview about therapeutic relevant and established biomarkers but also shed light on potential promising markers that may help us to better tailor therapy to the individual mCRC patient in the near future

Estado del conocimiento sobre peces nativos del altiplano cundiboyacense: revisión

Se presenta una recopilación bibliográfica de las referencias disponibles sobre tres especies endémicas del altiplano cundiboyacense: CAPITÁN de la SABANA (Eremophilus Mutisii), guapucha (Grundulus Bogotensis) y capitanejo o capitán enano (Trichomycterus Bogotense) como un documento de soporte para futuras investigaciones. De las tres especies, la mayor producción se presenta en E. Mutisii, en tanto que para T. Bogotense los registros son particularmente escasos. Por el tipo de documentos, se evidencia en general la falta de información básica y fundamental para la estructuración de programas de producción o conservación, lo cual es una limitante estratégica, máxime cuando se trata de especies consideradas como casi amenazada

The role of immunotherapy in microsatellites stable metastatic colorectal cancer: state of the art and future perspectives

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide, despite several advances has been achieved in last decades. Few prognostic and predictive biomarkers guide therapeutic choice in metastatic CRC (mCRC), among which DNA mismatch repair deficiency and/or microsatellite instability (dMMR/MSI) holds a crucial role. Tumors characterized by dMMR/MSI benefit from immune checkpoint inhibitors. However, most of the mCRC patients (around 95%) are microsatellite stable (MSS), thereby intrinsically resistant to immunotherapy. This represents a clear unmet need for more effective treatments in this population of patients. In this review, we aim to analyze immune-resistance mechanisms and therapeutic strategies to overcome them, such as combinations of immunotherapy and chemotherapy, radiotherapy or target therapies specifically in MSS mCRC. We also explored both available and potential biomarkers that may better select MSS mCRC patients for immunotherapy. Lastly, we provide a brief overview on future perspectives in this field, such as the gut microbiome and its potential role as immunomodulator

Optimización del uso de baterías en microrredes eléctricas

En este trabajo se estudia la gestión óptima del uso de baterías en una microrred eléctrica que incorpora fuentes de generación distribuida solares y eólicas. Se analiza el comportamiento de la microrred durante las 24 horas del día a lo largo de un mes, con las variaciones climáticas reales registradas durante el mes de febrero en la ciudad de Santa Fe, Argentina. El objetivo de la optimización consiste en determinar un cronograma horario óptimo de carga y descarga que minimice las pérdidas totales de la red. Como caso de estudio se analiza una versión modificada de la red de 15 nodos de la IEEE y se emplea el recocido simulado como algoritmo heurístico de optimización.Sociedad Argentina de Informática e Investigación Operativ

Optimización del uso de baterías en microrredes eléctricas

En este trabajo se estudia la gestión óptima del uso de baterías en una microrred eléctrica que incorpora fuentes de generación distribuida solares y eólicas. Se analiza el comportamiento de la microrred durante las 24 horas del día a lo largo de un mes, con las variaciones climáticas reales registradas durante el mes de febrero en la ciudad de Santa Fe, Argentina. El objetivo de la optimización consiste en determinar un cronograma horario óptimo de carga y descarga que minimice las pérdidas totales de la red. Como caso de estudio se analiza una versión modificada de la red de 15 nodos de la IEEE y se emplea el recocido simulado como algoritmo heurístico de optimización.Sociedad Argentina de Informática e Investigación Operativ

Optimización del uso de baterías en microrredes eléctricas

En este trabajo se estudia la gestión óptima del uso de baterías en una microrred eléctrica que incorpora fuentes de generación distribuida solares y eólicas. Se analiza el comportamiento de la microrred durante las 24 horas del día a lo largo de un mes, con las variaciones climáticas reales registradas durante el mes de febrero en la ciudad de Santa Fe, Argentina. El objetivo de la optimización consiste en determinar un cronograma horario óptimo de carga y descarga que minimice las pérdidas totales de la red. Como caso de estudio se analiza una versión modificada de la red de 15 nodos de la IEEE y se emplea el recocido simulado como algoritmo heurístico de optimización.Sociedad Argentina de Informática e Investigación Operativ

Landscape of KRASG12C, Associated Genomic Alterations, and Interrelation With Immuno-Oncology Biomarkers in KRAS-Mutated Cancers

Genomic alterations; Mutated cancers; Immuno-oncologyAlteraciones genómicas; Cánceres mutados; Inmuno-oncologíaAlteracions genòmiques; Càncers mutats; Immuno-oncologiaPURPOSE Promising single-agent activity from sotorasib and adagrasib in KRASG12C-mutant tumors has provided clinical evidence of effective KRAS signaling inhibition. However, comprehensive analysis of KRAS-variant prevalence, genomic alterations, and the relationship between KRAS and immuno-oncology biomarkers is lacking. MATERIALS AND METHODS Retrospective analysis of deidentified records from 79,004 patients with various cancers who underwent next-generation sequencing was performed. Fisher's exact test evaluated the association between cancer subtypes and KRAS variants. Logistic regression assessed KRASG12C comutations with other oncogenes and the association between KRAS variants and immuno-oncology biomarkers. RESULTS Of the 79,004 samples assessed, 13,758 (17.4%) harbored KRAS mutations, with 1,632 (11.9%) harboring KRASG12C and 12,126 (88.1%) harboring other KRAS variants (KRASnon-G12C). Compared with KRASnon-G12C across all tumor subtypes, KRASG12C was more prevalent in females (56% v 51%, false discovery rate-adjusted P value [FDR-P] = .0006), current or prior smokers (85% v 56%, FDR-P 60 years (73% v 63%, FDR-P ≤ .0001). The most frequent KRAS variants across all subtypes were G12D (29.5%), G12V (23.0%), G12C (11.9%), G13D (6.5%), and G12R (6.2%). KRASG12C was most prevalent in patients with non–small-cell lung cancer (9%), appendiceal (3.9%), colorectal (3.2%), tumor of unknown origin (1.6%), small bowel (1.43%), and pancreatic (1.3%) cancers. Compared with KRASnon-G12C-mutated, KRASG12C-mutated tumors were significantly associated with tumor mutational burden-high status (17.9% v 8.4%, odds ratio [OR] = 2.38; FDR-P < .0001). KRASG12C-mutated tumors exhibited a distinct comutation profile from KRASnon-G12C-mutated tumors, including higher comutations of STK11 (20.59% v 5.95%, OR = 4.10; FDR-P < .01) and KEAP1 (15.38% v 4.61%, OR = 3.76; FDR-P < .01). CONCLUSION This study presents the first large-scale, pan-cancer genomic characterization of KRASG12C. The KRASG12C mutation was more prevalent in females and older patients and appeared to be associated with smoking status. KRASG12C tumors exhibited a distinct comutation profile and were associated with tumor mutational burden-high status

Optimal Segmentation of Electrical Distribution Networks

New ways of generating electricity make possible decentralization of energy sources. This scenario of distributed generation allows efficient management of smaller electricity networks, so called microgrids. Additional advantages include a large reliability and the capability to provide a high quality of service. A strategy to design these microgrids consists on taking advantage of existing distribution network by sectoring the system into a set of microgrids with optimal autonomy. This paper presents a one-step methodology for the optimal design of microgrids based on the virtual segmentation of a distribution system. The proposed method focuses on the optimal allocation and sizing of the distributed generation together with the determination of the virtual cut-set lines to form an optimized set of microgrids. The design methodology was implemented on IEEE 119-bus system, and was also applied to Bella Italia distribution system, a real network located in Santa Fe province, Argentina.Fil: Bonetti, Carlos Alberto. Universidad Tecnológica Nacional. Facultad Regional Rafaela; ArgentinaFil: Bianchotti, J.D.. Universidad Tecnológica Nacional. Facultad Regional Rafaela; ArgentinaFil: Vega, Jorge Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Puccini, Gabriel Darío. Universidad Tecnológica Nacional. Facultad Regional Rafaela; Argentin

Real-world Outcomes of Relapsed/Refractory Diffuse Large B-cell Lymphoma Treated With Polatuzumab Vedotin-based Therapy

: After FDA and EMA approval of the regimen containing polatuzumab vedotin plus rituximab and bendamustine (PolaBR), eligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients in Italy were granted early access through a Named Patient Program. A multicentric observational retrospective study was conducted focusing on the effectiveness and safety of PolaBR in everyday clinical practice. Fifty-five patients were enrolled. There were 26 females (47.3%), 32 patients were primary refractory and 45 (81.8%) resulted refractory to their last therapy. The decision to add or not bendamustine was at physician's discretion. Thirty-six patients underwent PolaBR, and 19 PolaR. The 2 groups did not differ in most of baseline characteristics. The final overall response rate was 32.7% (18.2% complete response rate), with a best response rate of 49.1%. Median disease-free survival was reached at 12 months, median progression-free survival at 4.9 months and median overall survival at 9 months, respectively. Overall, 88 adverse events (AEs) were registered during treatment in 31 patients, 22 of grade ≥3. Eight cases of neuropathy occurred, all of grades 1-2 and all related to polatuzumab. The two groups of treatment did not differ for effectiveness endpoints but presented statistically significant difference in AEs occurrence, especially in hematological AEs, in AEs of grade equal or greater than 3 and in incidence of neuropathy. Our data add useful information on the effectiveness of Pola(B)R in the setting of heavily pretreated DLBCL and may also suggest a better tolerability in absence of bendamustine without compromise of efficacy

SARS-CoV-2 vaccination modelling for safe surgery to save lives: Data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population