Browsing by Author "Nervi, Bruno"

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    A snapshot of cancer in Chile: analytical frameworks for developing a cancer policy
    (2015) Jiménez de la Jara, Jorge; Bastías, Gabriel; Ferreccio Readi, Catterina; Moscoso, Cristián; Sagués, Sofía; Cid Pedraza, Camilo; Bronstein, Eduardo; Herrera Riquelme, Cristian Alberto; Nervi, Bruno; Corvalán R., Alejandro; Jiménez de la Jara, Jorge; Bastías, Gabriel; Ferreccio Readi, Catterina; Moscoso, Cristián; Sagués, Sofía; Cid Pedraza, Camilo; Bronstein, Eduardo; Herrera Riquelme, Cristian Alberto; Nervi, Bruno; Corvalán R., Alejandro
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    Benefit of adjuvant 5-fluorouracil based chemotherapy for colon cancer: a retrospective cohort study
    (SOC MEDICA SANTIAGO, 2016) Mondaca, Sebastian; Villalon, Constanza; Luis Leal, Jose; Zuniga, Alvaro; Bellolio, Felipe; Padilla, Oslando; Palma, Silvia; Garrido, Marcelo; Nervi, Bruno
    Background: Multiple clinical trials have demonstrated the benefits of adjuvant 5-fluorouracil-based chemotherapy for patients with resectable colon cancer (CC), especially in stage III. Aim: To describe the clinical characteristics of a cohort of CC patients treated at a single university hospital in Chile since 2002, and to investigate if chemotherapy had an effect on survival rates. Material and Methods: Review of a tumor registry of the hospital. Medical records of patients with CC treated between 2002 and 2012 were reviewed. Death certificates from the National Identification Service were used to determine mortality. Overall survival was described using the Kaplan-Meier method. A multivariate Cox proportional hazard regression model was also used. Results: A total of 370 patients were treated during the study period (202 in stage II and 168 in stage III). Adjuvant chemotherapy was administered to 22 and 70% of patients in stage II and III respectively. The median follow-up period was 4.6 years. The 5-year survival rate for stage II patients was 79% and there was no benefit observed with adjuvant chemotherapy. For stage III patients, the 5-year survival rate was 81% for patients who received adjuvant chemotherapy, compared to 56% for those who did not receive chemotherapy (hazard ratio (HR): 0.29; 95% confidence interval (CI): 0.15-0.56). The benefit of chemotherapy was found to persist after adjustment for other prognostic variables (HR: 0.47; 95% CI: 0.23-0.94). Conclusions: Patients with colon cancer in stage III who received adjuvant chemotherapy had a better overall survival.
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    Bone Marrow Stromal Cells Modulate Mouse ENT1 Activity and Protect Leukemia Cells from Cytarabine Induced Apoptosis
    (PUBLIC LIBRARY SCIENCE, 2012) Macanas Pirard, Patricia; Leisewitz, Andrea; Broekhuizen, Richard; Cautivo, Kelly; Barriga, Francisco M.; Leisewitz, Francisco; Gidi, Victoria; Riquelme, Erick; Montecinos, Viviana P.; Swett, Pilar; Besa, Pelayo; Ramirez, Pablo; Ocqueteau, Mauricio; Kalergis, Alexis M.; Holt, Matthew; Rettig, Michael; DiPersio, John F.; Nervi, Bruno
    Background: Despite a high response rate to chemotherapy, the majority of patients with acute myeloid leukemia (AML) are destined to relapse due to residual disease in the bone marrow (BM). The tumor microenvironment is increasingly being recognized as a critical factor in mediating cancer cell survival and drug resistance. In this study, we propose to identify mechanisms involved in the chemoprotection conferred by the BM stroma to leukemia cells.
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    Cholecystectomy and digestive cancer in Chile: Complementary results from interrupted time series and aggregated data analyses
    (2025) Gonzalez, Constanza; Garcia-Perez, Alfonso; Nervi, Bruno; Munoz, Cesar; Morales, Erik; Losada, Hector; Merino-Pereira, Gina; Rothhammer, Francisco; Bermejo, Justo Lorenzo
    Gallbladder cancer (GBC) mortality in Chile is among the highest worldwide. In 2006, the Chilean government launched a programme guaranteeing access to gallbladder surgery (cholecystectomy) for patients aged 35-49 years. We evaluated the impact of this programme on digestive cancer mortality. After conducting an interrupted time series analysis of hospitalisation and mortality data from 2002 to 2018 publicly available from the Chilean Department of Health Statistics and Information, we calculated the change in the proportion of individuals without gallbladder since 10 years. We then estimated age, gender, region, and calendar-year standardised mortality ratios (SMRs) as a function of the change in the proportion of individuals without gallbladder. The cholecystectomy rate increased by 45 operations per 100,000 persons per year (95%CI 19-72) after the introduction of the health programme. Each 1% increase in the proportion of individuals without gallbladder since 10 years was associated with a 0.73% decrease in GBC mortality (95% CI -1.05% to -0.38%), but the negative correlation was limited to women, southern Chile and age over 60. We also found decreasing mortality rates for extrahepatic bile duct, liver, oesophageal and stomach cancer with increasing proportions of individuals without gallbladder. To conclude, 12 years after its inception, the Chilean cholecystectomy programme has markedly and heterogeneously changed cholecystectomy rates. Results based on aggregate data indicate a negative correlation between the proportion of individuals without gallbladder and mortality due to gallbladder and other digestive cancers, which requires validation using individual-level longitudinal data to reduce the potential impact of ecological bias.
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    Complete response to immunotherapy plus chemotherapy after an unusual clinical response to afatinib and stereotactic radiosurgery in a patient with metastatic EGFR-mutant non–small-cell lung cancer
    (2020) Pizarro, Gonzalo; Pinto, Mauricio P.; Muñoz-Medel, Matías; Cordova-Delgado, Miguel; Bravo, M. Loreto; Nervi, Bruno; Sánchez, César; Ibañez, Carolina; Peña, José; Walbaum, Benjamín; Madrid, Jorge; Briones, Juan; Koch, Erica; Valbuena, Jose; Gonzalez, Sergio; Gejman, Roger; Acevedo, Francisco; Mondaca, Sebastian; Garrido, Marcelo; Vines, Eugenio; Galindo, Hector
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    Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high-incidence country
    (2023) Boekstegers, Felix; Scherer, Dominique; Barahona Ponce, Carol; Marcelain, Katherine; Garate-Calderon, Valentina; Waldenberger, Melanie; Morales, Erik; Rojas, Armando; Munoz, Cesar; Retamales, Javier; de Toro, Gonzalo; Barajas, Olga; Rivera, Maria Teresa; Cortes, Analia; Loader, Denisse; Saavedra, Javiera; Gutierrez, Lorena; Ortega, Alejandro; Bertran, Maria Enriqueta; Bartolotti, Leonardo; Gabler, Fernando; Campos, Monica; Alvarado, Juan; Moisan, Fabricio; Spencer, Loreto; Nervi, Bruno; Carvajal-Hausdorf, Daniel; Losada, Hector; Almau, Mauricio; Fernandez, Plinio; Olloquequi, Jordi; Fuentes-Guajardo, Macarena; Gonzalez-Jose, Rolando; Bortolini, Maria Catira; Acuna-Alonzo, Victor; Gallo, Carla; Linares, Andres Ruiz; Rothhammer, Francisco; Lorenzo Bermejo, Justo
    Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population-based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non-genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision-recall curve (AUC-PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC-PRC for the Baseline Model (0.44%, 95%CI 0.42-0.46) increased by 0.22 (95%CI 0.15-0.29) when non-genetic factors were included, and by 0.25 (95%CI 0.20-0.30) when incorporating non-genetic and genetic factors. The overall NCN for Chileans with gallstones (115, 95%CI 104-131) decreased to 92 (95%CI 60-128) for Chileans with a higher risk than the median according to Enhanced Model I, and to 80 (95%CI 59-110) according to Enhanced Model II. In conclusion, age, sex and gallstones are strong risk factors for GBC, but consideration of other non-genetic factors and individual genotype data improves risk prediction and may optimize allocation of financial resources and surgical capacity.
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    Early Anti-SARS-CoV-2 Convalescent Plasma in Patients Admitted for COVID-19: A Randomized Phase II Clinical Trial
    (2020) Balcells, María Elvira ; Rojas, Luis ; Le Corre, Nicole ; Martínez-Valdebenito, Constanza ; Ceballos, María Elena ; Ferrés, Marcela ; Chang, Mayling ; Vizcaya, Cecilia ; Mondaca, Sebastián ; Huete, Álvaro ; Castro, Ricardo ; Sarmiento, Mauricio ; Villarroel, Luis ; Pizarro, Alejandra; Ross, Patricio ; Santander, Jaime ; Lara, Barbara ; Ferrada, Marcela ; Vargas-Salas, Sergio ; Beltrán-Pavez, Carolina ; Soto-Rifo, Ricardo ; Valiente-Echeverría, Fernando ; Caglevic, Christian ; Mahave, Mauricio ; Selman, Carolina ; Gazitúa, Raimundo ; Briones, José Luis ; Villarroel-Espindola, Franz ; Balmaceda, Carlos ; Espinoza, Manuel A. ; Pereira, Jaime ; Nervi, Bruno
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    First-line endocrine therapy for advanced breast cancer. A real-world study at a Latin American university health institution
    (TAYLOR & FRANCIS LTD, 2020) Walbaum, Benjamin; Acevedo, Francisco; Medina, Lidia; Bravo, M. Loreto; Merino, Tomas; Camus, Mauricio; Dominguez, Francisco; Mondaca, Sebastian; Galindo, Hector; Nervi, Bruno; Ibanez, Carolina; Madrid, Jorge; Pena, Jose; Koch, Erica; Garrido, Marcelo; Pinto, Mauricio P.; Sanchez, Cesar
    Objective: Clinical guidelines recommend the use of endocrine therapy (ET) in advanced hormone receptor positive (HR+) human epidermal growth factor receptor type 2 negative (HER2-) breast cancer (BC) patients in the absence of visceral disease or ET resistance. Furthermore, studies indicate similar response and survival rates using ET or cytotoxic chemotherapy (CT). Methods: Herein, we assessed clinical characteristics, type of systemic therapy and survival rates of advanced HR + HER2-BC patients in our database. Results: A total of 172 advanced HR + HER2-BC patients were treated at our institution between 1997 and 2019. Sixty percent received first-line ET (4% received combined ET). Median age of this subset was 55 years (range: 30-86). Similarly, the median age of patients that received CT was 54 years (range: 21-83). Over time, 30% of patients received ET in the 2000-2005 period; this increased to 70% in the 2016-2019 period (p = .045). Overall survival (OS) was 97 months and 51 months for patients treated with ET or CT, respectively (p = .002). Conclusions: To the best of our knowledge this is the first study assessing the use of ET in Chilean advanced HR + HER2-BC patients. Several patients in our institution receive CT without indication. The increase in ET usage over time can be attributed to better and faster immunohistochemical detection methods for Estrogen Receptor (ER), changes in educational and government policies, and a wider variety of ET options. Finally, clinical trials have failed to demonstrate a substantial benefit of CT over ET in this setting.
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    Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression
    (2022) Blandino, Alice; Scherer, Dominique; Rounge, Trine B.; Umu, Sinan U.; Boekstegers, Felix; Barahona Ponce, Carol; Marcelain, Katherine; Garate-Calderon, Valentina; Waldenberger, Melanie; Morales, Erik; Rojas, Armando; Munoz, Cesar; Retamales, Javier; de Toro, Gonzalo; Barajas, Olga; Rivera, Maria Teresa; Cortes, Analia; Loader, Denisse; Saavedra, Javiera; Gutierrez, Lorena; Ortega, Alejandro; Bertran, Maria Enriqueta; Gabler, Fernando; Campos, Monica; Alvarado, Juan; Moisan, Fabrizio; Spencer, Loreto; Nervi, Bruno; Carvajal-Hausdorf, Daniel E.; Losada, Hector; Almau, Mauricio; Fernandez, Plinio; Gallegos, Ivan; Olloquequi, Jordi; Fuentes-Guajardo, Macarena; Gonzalez-Jose, Rolando; Bortolini, Maria Catira; Gallo, Carla; Linares, Andres Ruiz; Rothhammer, Francisco; Lorenzo Bermejo, Justo
    Simple Summary Gallbladder cancer (GBC) is an aggressive disease with poor prognosis that urgently needs risk biomarkers for prevention. Long noncoding RNAs (lncRNAs) have been linked to various types of cancer and have good potential as circulating biomarkers. Prediction of lncRNA expression based on genotype data may contribute to quantify individual GBC risk even without direct lncRNA expression measurement. In this study, we investigate the relationship between GBC risk and genotype-based expression of circulating lncRNAs. Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC) using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence "gallstones -> dysplasia -> GBC". In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncRNAs (cis-lncRNA-eQTLs) and build lncRNA expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes and assess the association between genotype-based expression and GBC risk. AC084082.3 and LINC00662 showed increasing expression levels (p-value = 0.009), while C22orf34 expression decreased in the sequence from gallstones to GBC (p-value = 0.04). We identified and validated two cis-LINC00662-eQTLs (r(2) = 0.26) and three cis-C22orf34-eQTLs (r(2) = 0.24). Only LINC00662 showed a genotyped-based serum expression associated with GBC risk (OR = 1.25 per log2 expression unit, 95% CI 1.04-1.52, p-value = 0.02). Our results suggest that preselection of lncRNAs based on tissue samples and exploitation of cis-lncRNA-eQTLs may facilitate the identification of circulating noncoding RNAs linked to cancer risk.
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    ' IHPBA-APHPBA clinical practice guidelines': international Delphi consensus recommendations for gallbladder cancer
    (2024) Palepu, Jagannath; Endo, Itaru; Chaudhari, Vikram Anil; Murthy, G. V. S.; Chaudhuri, Sirshendu; Adam, Rene; Smith, Martin; de Reuver, Philip R.; Lendoire, Javier; Shrikhande, Shailesh, V; De Aretxabala, Xabier; Sirohi, Bhawna; Kokudo, Norihiro; Kwon, Wooil; Pal, Sujoy; Bouzid, Chafik; Dixon, Elijah; Shah, Sudeep Rohit; Maroni, Rodrigo; Nervi, Bruno; Mengoa, Claudio; Patil, Shekhar; Ebata, Tomoki; Maithel, Shishir K.; Lang, Hauke; Primrose, John; Hirano, Satoshi; Guevara, Oscar A.; Ohtsuka, Masayuki; Valle, Juan W.; Sharma, Atul; Nagarajan, Ganesh; Ju, Juan Jose Nunez; Arroyo, Gerardo Francisco; Torrez, Sergio Lopez; Erdmann, Joris Ivo; Butte, Jean M.; Furuse, Junji; Lee, Seung Eun; Gomes, Antonio Pedro; Park, Sang-Jae; Jang, Jin-Young; Oddi, Ricardo; Barreto, Savio George; Kijima, Hiroshi; Ciacio, Oriana; Gowda, Nagesh S.; Jarnagin, William
    Background: The Delphi consensus study was carried out under the auspices of the International and Asia-Pacific Hepato-Pancreato-Biliary Associations (IHPBA-APHPBA) to develop practice guidelines for management of gallbladder cancer (GBC) globally. Method: GBC experts from 17 countries, spanning 6 continents, participated in a hybrid four-round Delphi consensus development process. The methodology involved email, online consultations, and in-person discussions. Sixty eight clinical questions (CQs) covering various domains related to GBC, were administered to the experts. A consensus recommendation was accepted only when endorsed by more than 75% of the participating experts. Results: Out of the sixty experts invited initially to participate in the consensus process 45 (75%) responded to the invitation. The consensus was achieved in 92.6% (63/68) of the CQs. Consensus covers epidemiological aspects of GBC, early, incidental and advanced GBC management, definitions for radical GBC resections, the extent of liver resection, lymph node dissection, and definitions of borderline resectable and locally advanced GBC. Conclusions: This is the first international Delphi consensus on GBC. These recommendations provide uniform terminology and practical clinical guidelines on the current management of GBC. Unresolved contentious issues like borderline resectable/locally advanced GBC need to be addressed by future clinical studies.
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    Kinetic of humoral response induced by SARS-CoV-2 infection in convalescent plasma receptors and donors
    (WILEY, 2021) Barrera, Aldo; Martinez Valdebenito, Constanza; Rojas Orellana, Luis; Vizcaya Altamirano, Cecilia; Elena Ceballos, Maria; Pereira, Jaime; Chang, Mayling; Mondaca, Sebastian; Sarmiento, Mauricio; Ross, Patricio; Henriquez, Carolina; Nervi, Bruno; Ferres, Marcela; Balcells, Elvira; Le Corre, Nicole
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    Oncological resection, myasthenia gravis and staging as prognostic factors in thymic tumours: a Chilean case series
    (2021) Salas, Patricio; Solovera, Maria Eliana; Bannura, Felipe; Muñoz-Medel, Matias; Cordova-Delgado, Miguel; Sanchez, Cesar; Ibañez, Carolina; Garrido, Marcelo; Koch, Erica; Acevedo, Francisco; Mondaca, Sebastian; Nervi, Bruno; Madrid, Jorge; Peña, Jose; Pinto, Mauricio P.; Valbuena, José; Galindo, Hector
    Background: Thymic epithelial tumours are rare and highly heterogeneous. Reports from the United States suggest an overall incidence of 0.15 per 100,000/year. In contrast, the incidence of these tumours in Latin America is largely unknown and reports are scarce, somewhat limited to case reports. Methods: Herein, we report a series of 38 thymic tumours from a single institution, retrospectively incorporated into this study. Patient characteristics and outcomes including age, sex, stage, paraneoplastic syndromes, treatment regimens and the date of decease were obtained from medical records. Results: Most cases in our series were females and young age (<50 years old) and early stage by Masaoka-Koga or the Moran staging systems. Also, a 34% of patients had myasthenia gravis (MG). Next, we analysed overall survival rates in our series and found that the quality of surgery (R0, R1 or R2), MG status and staging (Masaoka-Koga, Moran or TNM) were prognostic factors. Finally, we compared our data to larger thymic tumour series. Conclusions: Overall, our study confirms complete surgical resection as the standard, most effective treatment for thymic epithelial tumours. Also, the Masaoka-Koga staging system remains as a reliable prognostic factor but also the Moran staging system should be considered for thymomas.
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    Pathological complete response to neoadjuvant chemotherapy, but not the addition of carboplatin, is associated with improved survival in Chilean triple negative breast cancer patients: a report of real world data
    (2021) Walbaum, Benjamin; Acevedo, Francisco; Median, Lidia; Bravo, M. Loreto; Merino, Tomas; Camus, Mauricio; Dominguez, Francisco; Mondaca, Sebastián; Galindo, Héctor; Nervi, Bruno; Ibañez, Carolina; Madrid, Jorge; Muñiz, Sabrina; Peña, José; Koch, Érica; Garrido, Marcelo; Pinto, Mauricio P.; Sánchez, César
    Background: Breast cancer (BC) is the leading cause of cancer death for Chilean women. About 11% of cases are triple-negative (TN) BC. These are characterised by poor prognosis, higher risk of early recurrence and visceral dissemination versus other BC subtypes. Current standard treatment for early-stage non-metastatic TNBC patients consists of neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy. Pathological complete response (pCR) to NACT is associated with an increase in survival rates. In general, NACT and adjuvant regimens involve similar cytotoxic drugs. Recent studies have postulated that the use of platinum compounds in TNBC would increase response rates. However, their effects on patient survival remain uncertain. Materials and methods: We retrieved and analysed medical records from a total of 156 Chilean stage I–III TNBC female patients that received NACT and compared survival rates using carboplatin (Cb)-containing versus non-Cb-containing regimens at two health cancer centres. Results: Median age was 51 years (range: 24–81); 13.5% (n = 21) received Cb-containing regimens, 80.1% (n = 125) received sequential anthracyclines plus taxanes; 29.5% (n = 46) of the total group achieved pCR, 28% for the standard treatment and 35% (n = 8) for the Cb-containing group (p = 0.59). We confirmed pCR was associated with prolonged overall survival, invasive and distant disease-free survival (Log-rank p = 0.0236). But the addition of Cb was not associated with differences in survival measures (Log-rank p = 0.5216). Conclusions: To the best of authors’ knowledge, this is the first report on real-world data in the Chilean population assessing the effect of Cb-containing NACT in TNBC. The authors’ results suggest no survival benefit by the addition of Cb to standard NACT. However, we confirm an increase in survival associated to pCR regardless of treatment.
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    Prophylaxis against cytomegalovirus infection in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation
    (SOC CHILENA INFECTOLOGIA, 2012) Ferres, Marcela; Nervi, Bruno; Ramirez, Pablo
    CMV is one of the main infectious problems for SOT and HSCT. The severity of the complications are mainly associated with the type of transplant and immune status against the virus of the transplant donor and the transplant recipient. It is important to prevent exposure, using safe blood transfusion CMV seronegative donors (B1) and/or use of blood leucocytes-depleted by filtration (A1). In addition to preventing exposure, there are two widely used prevention strategies: universal prophylaxis with antiviral therapy or "pre-emptive" strategy based on the use of antivirals only to the early detection of CMV replication in blood. The first option is most used in the SOT management, especially for those identified as the high risk group of CMV disease: R (+), with D (+) or D (-) (A1), where the recommended drug is ganciclovir or valganciclovir. The second approach is preferable for HSCT, which recommends weekly monitoring for CMV viral load from day 10 to 100 post transplant (A3). This strategy requires having a viral laboratory support (A2). The selected antiviral in the case of pre emptive therapy is intravenous ganciclovir (A1).
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    Resistance of leukemia cells to cytarabine chemotherapy is mediated by bone marrow stroma, involves cell-surface equilibrative nucleoside transporter-1 removal and correlates with patient outcome
    (2017) Macanas Pirard, Patricia; Broekhuizen, Richard; González, Alfonso; Oyanadel, Claudia; Ernst Diaz, Daniel Matias; García Cañete, Patricia; Montecinos Acuña, Viviana; Court G., Felipe; Ocqueteau Tachini, Mauricio; Ramírez Villanueva, Pablo Antonio; Nervi, Bruno
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    SARS-CoV-2 infectivity and antigenic evasion: spotlight on isolated Omicron sub-lineages
    (2024) Barrera, Aldo; Martinez-Valdebenito, Constanza; Angulo, Jenniffer; Palma, Carlos; Hormazabal, Juan; Vial, Cecilia; Aguilera, Ximena; Castillo-Torres, Pablo; Pardo-Roa, Catalina; Balcells, Maria Elvira; Nervi, Bruno; Le Corre, Nicole; Ferres, Marcela
    Since the SARS-CoV-2 outbreak in 2019, a diversity of viral genomic variants has emerged and spread globally due to increased transmissibility, pathogenicity, and immune evasion. By the first trimester of 2023 in Chile, as in most countries, BQ and XBB were the predominant circulating sub-lineages of Omicron. The molecular and antigenic characteristics of these variants have been mainly determined using non-authentic spike pseudoviruses, which is often described as a limitation. Additionally, few comparative studies using isolates from recent Omicron sub-lineages have been conducted. In this study, we isolated SARS-CoV-2 variants from clinical samples, including the ancestral B.1.1, Delta, Omicron BA.1, and sub-lineages of BA.2 and BA.5. We assessed their infectivity through cell culture infections and their antibody evasion using neutralization assays. We observed variations in viral plaque size, cell morphology, and cytotoxicity upon infection in Vero E6-TMPRSS2 cells for each variant compared to the ancestral B.1.1 virus. BA.2-derived sub-variants, such as XBB.1.5, showed attenuated viral replication, while BA.5-derived variants, such as BQ.1.1, exhibited replication rates similar to the ancestral SARS-CoV-2 virus. Similar trends were observed in intestinal Caco-2 cells, except for Delta. Antibody neutralization experiments using sera from individuals infected during the first COVID-19 wave (FWI) showed a consistent but moderate reduction in neutralization against Omicron sub-lineages. Interestingly, despite being less prevalent, BQ.1.1 showed a 6.1-fold greater escape from neutralization than XBB.1.5. Neutralization patterns were similar when tested against sera from individuals vaccinated with 3xBNT162b2 (PPP) or Coronavac-Coronavac-BNT162b2 (CCP) schedules. However, CCP sera showed 2.3-fold higher neutralization against XBB.1.5 than FWI and PPP sera. This study provides new insights into the differences between BA.2 and BA.5-derived variants, leading to their eventual outcompetition. Our analysis offers important evidence regarding the balance between infectivity and antigenic escape that drives the evolution of second-generation SARS-CoV-2 variants in the population.
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    Thalidomide for the treatment of metastatic hepatic epithelioid hemangioendothelioma: A case report with a long term follow-up
    (ELSEVIER ESPANA, 2011) Salech, Felipe; Valderrama, Sebastian; Nervi, Bruno; Carlos Rodriguez, Juan; Oksenberg, Danny; Koch, Alvaro; Smok, Gladys; Duarte, Ignacio; Maria Perez Ayuso, Rosa; Jarufe, Nicolas; Martinez, Jorge; Soza, Alejandro; Arrese, Marco; Riquelme, Arnoldo
    Hepatic epithelioid hemangioendothelioma (HEH) is an unusual, low-grade malignant vascular tumor of the liver. Here we describe a case of a 40-year-old woman who presented with abdominal pain in the upper right quadrant and giant hepatomegaly, in which imaging studies and a fine-needle liver biopsy confirmed the presence of a large EHE with an isolated lung metastasis. After balancing all possible therapeutic modalities the patient was treated conservatively with thalidomide (300 mg/day). The drug was well tolerated with minimal toxicity and the patient continues on therapy 109 months after treatment was started with no disease progression. Current therapeutic options for HEH are discussed in light of the clinical case with particular emphasis on anti-angiogenic therapies.