Pesticides in water and sediments from natural protected areas of Spain and their associated ecological risk.

In the last years, issues related to intensive agriculture have been found in protected areas potentially harming wildlife. This study aimed to analyze a wide range of pesticides in water and sediments of two protected areas namely Doñana Natural Park (DNP) and Tablas de Daimiel National Park (TDNP) performing an environmental risk assessment in order to highlight potential risks to living organisms derived from pesticide burden. Higher pesticide load was found in DNP than TDNP with similar distribution profiles, with pyrethroid insecticides (PYRs) the main detected class. Particularly problematic are two PYRs, cyhalothrin and fenvalerate, which were detected at high concentrations that can pose a high risk to aquatic organisms. In addition, despite being detected at lower concentrations, the presence of chlorpyrifos, cypermethrin, and permethrin in water, and of chlorpyrifos, dicofol, and diflufenican in sediments, must be taken into account due to their potential risks for aquatic organisms. Moreover, some banned pesticides such as dimethoate, terbutryn, diazinon, and tricyclazol were detected in water at levels which deserve further investigation to assess their potential sources, including potential illegal practices.

Nanoparticle-mediated thermal Cancer therapies: Strategies to improve clinical translatability.

Despite significant advances, cancer remains a leading global cause of death. Current therapies often fail due to incomplete tumor removal and nonspecific targeting, spurring interest in alternative treatments. Hyperthermia, which uses elevated temperatures to kill cancer cells or boost their sensitivity to radio/chemotherapy, has emerged as a promising alternative. Recent advancements employ nanoparticles (NPs) as heat mediators for selective cancer cell destruction, minimizing damage to healthy tissues. This approach, known as NP hyperthermia, falls into two categories: photothermal therapies (PTT) and magnetothermal therapies (MTT). PTT utilizes NPs that convert light to heat, while MTT uses magnetic NPs activated by alternating magnetic fields (AMF), both achieving localized tumor damage. These methods offer advantages like precise targeting, minimal invasiveness, and reduced systemic toxicity. However, the efficacy of NP hyperthermia depends on many factors, in particular, the NP properties, the tumor microenvironment (TME), and TME-NP interactions. Optimizing this treatment requires accurate heat monitoring strategies, such as nanothermometry and biologically relevant screening models that can better mimic the physiological features of the tumor in the human body. This review explores the state-of-the-art in NP-mediated cancer hyperthermia, discussing available nanomaterials, their strengths and weaknesses, characterization methods, and future directions. Our particular focus lies in preclinical NP screening techniques, providing an updated perspective on their efficacy and relevance in the journey towards clinical trials.

Transcaval approach for aortic endoprosthesis insertion. A new anesthetic challenge.

The treatment of acute aortic syndrome has been benefited in recent years from the huge progress in endovascular techniques, compared to classical surgical treatment, by open surgery. Nevertheless, for endovascular treatment to be successful, it is essential for the patient to present adequate vascular access. Those cases with unfavourable vascular anatomy make it necessary to consider open surgery with significant morbidity, or even to reject surgery. A new approach to the abdominal aorta has recently been described as an indication for these patients with impossibility of other vascular access and absolute or relative contraindication to the transthoracic approach. The anesthetic management of the aortic syndrome is well known and, even though there are a variety of options, all of them have proven safety and efficacy. The implementation of new surgical approaches and new possible complications imply a challenge for the anesthesiologist which, for now, has little or none scientific evidence. We present the first case of transcaval aortic endoprosthesis implantation in Spain, its anesthetic implications, and a review of the literature.

High linoleic acid levels in red blood cells predict a poor response to neoadjuvant chemotherapy in human epidermal growth factor receptor type 2-positive breast cancer patients.

OBJECTIVE: Polyunsaturated fatty acids are categorized as ω-3 or ⍵-6. Previous studies demonstrate that breast cancers display a high expression of fatty acid synthase and high fatty acid levels. Our study sought to determine if changes in plasma or red blood cell membrane fatty acid levels were associated with the response to preoperative (neoadjuvant) chemotherapy in non-metastatic breast cancer patients. METHODS: Our prospective study assessed fatty acid levels in plasma and red blood cell membrane. Response to neoadjuvant chemotherapy was evaluated by the presence or absence of pathologic complete response and/or residual cancer burden. RESULTS: A total of 28 patients were included. First, patients who achieved pathologic complete response had significantly higher neutrophil-to-lymphocyte ratio versus no pathologic complete response (P = 0.003). Second, total red blood cell membrane polyunsaturated fatty acids were higher in the absence of pathologic complete response (P = 0.0028). Third, total red blood cell membrane ⍵-6 polyunsaturated fatty acids were also higher in no pathologic complete response (P < 0.01). Among ⍵-6 polyunsaturated fatty acids, red blood cell membrane linoleic acid was higher in the absence of pathologic complete response (P < 0.01). Notably, plasma polyunsaturated fatty acid, ⍵-6, and linoleic acid levels did not have significant differences. A multivariate analysis confirmed red blood cell membrane linoleic acid was associated with no pathologic complete response; this was further confirmed by receiver operating characteristic analysis (specificity = 92.3%, sensitivity = 76.9%, and area under the curve = 0.855). CONCLUSIONS: Pending further validation, red blood cell membrane linoleic acid might serve as a predictor biomarker of poorer response to neoadjuvant chemotherapy in non-metastatic human epidermal growth factor receptor type 2-positive breast cancer. Measuring fatty acids in red blood cell membrane could offer a convenient, minimally invasive strategy to identifying patients more likely to respond or those with chemoresistance.

Hidrocistomas ecrinos múltiples

RESUMEN Los hidrocistomas ecrinos son tumores benignos, únicos o múltiples. Se presentan con mayor frecuencia en la mediana edad y predominan en el sexo femenino. Se presenta un paciente con hidrocistomas ecrinos múltiples, masculino de 74 años.

ABSTRACT Eccrine hydrocystomas are benign tumors, which can be single or multiple. They occur most oftenly in middle aged patients or in the elderly, predominantly female. We present a case of multiple eccrine hydrocystomas, in a 74-year-old male patient.

Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study.

BACKGROUND: Patritumab deruxtecan (HER3-DXd) is a human epidermal growth factor receptor 3 (HER3)-directed antibody-drug conjugate composed of a fully human anti-HER3 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. TOT-HER3 is a window-of-opportunity study designed to assess the biological activity, measured by CelTIL score [= -0.8 × tumor cellularity (in %)  + 1.3  × tumor-infiltrating lymphocytes (TILs) (in %)], and clinical activity of HER3-DXd during short-term (21 days) pre-operative treatment in patients with primary operable HER2-negative early breast cancer. PATIENTS AND METHODS: Patients with previously untreated hormone receptor-positive/HER2-negative tumors were allocated to one of four cohorts according to baseline ERBB3 messenger RNA expression. All patients received one dose of HER3-DXd 6.4 mg/kg. The primary objective was to evaluate change from baseline in CelTIL score. RESULTS: Seventy-seven patients were evaluated for efficacy. A significant change in CelTIL score was observed, with a median increase from baseline of 3.5 (interquartile range, -3.8 to 12.7; P = 0.003). Among patients assessable for clinical response (n = 62), an overall response rate of 45% was observed (tumor measurement by caliper), with a trend toward an increase in CelTIL score among responders compared with non-responders (mean difference, +11.9 versus +1.9). Change in CelTIL score was independent of baseline ERBB3 messenger RNA and HER3 protein levels. Genomic changes occurred, including switching toward a less proliferative tumor phenotype based on PAM50 subtypes, suppression of cell proliferation genes, and induction of genes associated with immunity. Treatment-emergent adverse events were observed in 96% of patients (14% grade ≥3); most common were nausea, fatigue, alopecia, diarrhea, vomiting, abdominal pain, and neutrophil count decrease. CONCLUSIONS: A single dose of HER3-DXd was associated with clinical response, increased immune infiltration, suppression of proliferation in hormone receptor-positive/HER2-negative early breast cancer, and a tolerable safety profile consistent with previously reported results. These findings support further study of HER3-DXd in early breast cancer.

Access disparities and underutilization of germline genetic testing in Chilean breast cancer patients.

PURPOSE: Latin American reports on genetic cancer risk assessments are scarce. In Chile, current breast cancer (BC) guidelines do not define strategies for germline genetic testing. Our study sought to quantify the disparities in access to genetic testing in Chilean BC patients, according to international standards and their clinical characteristics to explore improvement strategies. METHODS: Retrospective analysis of invasive BC databases including patients treated in a Public Hospital (PH) and in an Academic Private Center (AC) in Santiago, Chile between 2012 and 2021. RESULTS: Of 5438 BC patients, 3955 had enough data for National Comprehensive Cancer Network (NCCN) categorization. From these, 1911 (48.3%) fulfilled NCCN criteria for germline testing, of whom, 300 were tested for germline mutations and 268 with multigene panels. A total of 65 pathogenic variants were found in this subset. As expected, BRCA1/2 mutations were the most frequent (17.7%). Access to genetic testing was higher in AC versus PH (19.6% vs. 10.3%, p = 0.0001). Other variables associated with germline genetic testing were BC diagnosis after 2018, being 45 years old or younger at diagnosis, BC family history (FH), FH of ovarian cancer, non-metastatic disease, and triple-negative subtype. CONCLUSION: In our cohort, 15% of BC patients who met NCCN criteria for germline testing were effectively tested. This percentage was even lower at the PH. Current recommendations encourage universal genetic testing for BC patients; however, our findings suggest that Chile is far from reaching such a goal and national guidelines in this regard are urgently needed. To our knowledge, this is the first study of its kind in Chile and Latin America.

Systematic mapping review of interventions to prevent blood loss, infection and relapse in orthognathic surgery.

BACKGROUND: This systematic mapping review aims to identify, describe, and organize the currently available evidence in systematic reviews (SR) and primary studies regarding orthognathic surgery (OS) co-interventions and surgical modalities, focusing on the outcomes blood loss, infection and relapse. MATERIAL AND METHODS: A comprehensive search strategy was performed to identify all SRs, randomized controlled trials and observational studies that evaluate surgical modalities and perioperative co-interventions in OS that evaluate the outcomes blood loss, infection and relapse, regardless of language or publication date. Searches were conducted in MEDLINE, EMBASE, Epistemonikos, Lilacs, Web of Science, and CENTRAL. In addition, grey literature was screened. RESULTS: 27 SRs and 150 primary studies fulfilled the inclusion criteria, 91 from SRs, and 59 from our search strategy. Overall, the quality of the SRs was graded as "Critically low," and only two SRs were rated as "High" quality. 11 PICO questions were extracted from SRs and 31 from primary studies, which focused on osteosynthesis methods, surgical cutting devices, use of antibiotics, and induced hypotension. In addition, evidence bubble maps for each outcome were created to analyze in a visual manner the existing evidence. CONCLUSIONS: Future primary and secondary high-quality research should be addressed focused on the eight knowledge gaps identified in this mapping review. We concluded that the evidence mapping approach is a practical methodology for organizing the current evidence and identifying knowledge gaps in OS, helping to reduce research waste and canalize future efforts in developing studies for unsolved questions.

Human papillomavirus infection and lung adenocarcinoma: special benefit is observed in patients treated with immune checkpoint inhibitors.

BACKGROUND: Human papilloma virus (HPV) has been associated with the development and modulation of response in a series of neoplasms. In the case of lung adenocarcinoma, its role in etiology and pathogenesis is still controversial. Considering that this infection brings foreign epitopes, it could be of prognostic significance in patients with lung adenocarcinoma treated with immunotherapy. METHODS: In a retrospective cohort study we evaluated the presence of HPV genomic material in lung adenocarcinoma primary lesions with the INNO-LiPA platform. Viral replication was also evaluated by detecting the presence of oncoprotein E6/E7 messenger RNA (mRNA) by quantitative RT-PCR. To confirm possible hypotheses regarding viral oncogenesis, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF1) were evaluated with stromal fibrosis and immunoscore. RESULTS: A total of 133 patients were included in the analysis, of whom 34 tested positive for HPV, reaching an estimated prevalence of 25.6% [95% confidence interval (CI) 18.2% to 32.9%]. E6/7 mRNA was identified in 28 out of the 34 previously positive cases (82.3%). In immune checkpoint inhibitor (ICI)-treated patients, the median overall survival reached 22.3 months [95% CI 19.4 months- not reached (NR)] for HPV-negative and was not reached in HPV-positive (HPV+) ones (95% CI 27.7-NR; P = 0.008). With regard to progression-free survival, HPV- patients reached a median of 9.2 months (95% CI 7.9-11.2 months) compared to 14.3 months (95% CI 13.8-16.4 months) when HPV was positive (P = 0.001). The overall response rate for HPV+ patients yielded 82.4% compared to 47.1% in negative ones. No differences regarding programmed death-ligand 1, VEGF, HIF1, stromal fibrosis, or immunoscore were identified. CONCLUSIONS: In patients with HPV+ lung adenocarcinoma, a significant benefit in overall response and survival outcomes is observed.

Effectiveness of glucocorticoids in orthognathic surgery: an overview of systematic reviews.

For decades, short-term glucocorticoids have been advocated to reduce postoperative swelling, pain, trismus, and nausea and vomiting in patients experiencing maxillofacial surgeries. The purpose of this systematic overview was to identify and assess the best evidence regarding the efficacy of glucocorticoid administration in patients who undergo orthognathic surgery. Five databases (Medline, Embase, The Cochrane Library, Web of Science, and Epistemonikos) were searched from their inception to October 2020. The risk of bias assessment was performed using the ROBIS tool, and the quality of the evidence reported was rated using the GRADE approach. Six systematic reviews were identified, of which three were included in this overview (n=527). According to the rating of the overall risk of bias, one achieved a low score and two were rated as high. The quality of the evidence reported ranged from very low to moderate. Corticoids may reduce the incidence of moderate or severe postoperative nausea and vomiting in the early postoperative period (0-6 hours) compared to metoclopramide, but the evidence is very uncertain. Some significant therapeutic effects on neurosensory recovery have been reported, but there was inconsistency across the studies. Finally, based on a moderate quality of evidence, it is possible to establish that the administration of glucocorticoids is likely to reduce oedema in the early postoperative period (0-48 hours) in patients who undergo orthognathic surgery, and to have no significant adverse effects. Further quantitative syntheses based on well-designed and standardised clinical studies are suggested to determine direction and strength of the intervention on the other outcomes.

Asociación del nivel socioeconómico y educacional en los egresos por cáncer de mama en Chile durante los años 2001 al 2016 / Association of the socioeconomic and educational level in the breast cancer hospital outbreaks in Chile during the years 2001 to 2016

Introducción: El cáncer de mama constituye la primera causa de muerte en los cánceres en Chile según Globocan 2018. Dentro de los factores que explican esta alta mortalidad encontramos una baja tasa de detección y de realización de mamografías en los niveles socioeconómicos altos. Es por esto que comprender las causas de defunción y los factores que afectan en la mortalidad y letalidad por cáncer de mama en los últimos 17 años nos permitirá enfocar las políticas públicas de los próximos 50 años. Los objetivos generales de este trabajo fueron caracterizar los egresos hospitalarios en los pacientes por cáncer de mama según la edad, el sexo, la previsión, el nivel socioeconómico y educacional en Chile durante los años 2001 al 2016 y calcular la mortalidad y letalidad específica en estas mismas variables durante los años 2001 a 2016. El objetivo específico es asociar las variables socioeconómicas y educacionales, estimando los Odd's ratios de las variables en los egresos hospitalarios por cáncer de mama en Chile durante los años 2001 al 2016. Materiales y Métodos: Estudio de cohorte longitudinal retrospectivo en 81,072 egresos hospitalarios y 20,220 defunciones obtenidas de la página DEIS MINSAL, años 2001-2016. Para el análisis univariado se efectuó una regresión de ajuste de tasas Prais-weinstein según edad y sexo según modelo OMS de ajuste de tasas. Para las variables de tipo discreta se describieron mediante porcentajes y tasas y para las variables de tipo continua se utilizó mediana y desviación estándar. Se efectuó un test de smirnov-kolmolgorov para determinar el tipo de distribución y de normalidad de las muestras. Para las variables de tipo dicotómica se utilizó un modelo de regresión logística binaria para describir estas variables y determinar la posible asociación entre el nivel socioeconómico y educacional de las pacientes diagnosticadas por cáncer de mama. Resultados: Murieron 1,88 veces más personas de nivel socioeconómico alto con un IC entre 1,83- 1,94 con respecto a la población de nivel socioeconómico bajo. En cambio, las personas con un mayor nivel educacional murieron 0,5 veces menos según la regresión realizada respecto al bajo nivel educacional con un IC entre 0,47- 0,52, pero a menor nivel educacional aumentó 20 veces la mortalidad, constituyendo una causa inversa. Respecto al sexo las mujeres murieron 2,08 veces más que los hombres. Para el nivel socioeconómico alto en relación al bajo un OR [1.88 (1.83 a 1,94)], p<0,0001], para el nivel educacional alto en relación al bajo fue a favor del mayor nivel educacional con OR [0,5 (0,47 - 0,52)] y en cuanto a la comparación de sexos un OR [1,04 (1,03-2,17), p=0,039]. Es decir, la diferencia entre mortalidad que hubo fue significativa para todos los intervalos tanto para sexo, nivel educacional como para nivel socioeconómico. Se encontró una constante de 0,013 de mortalidad basal, es decir, todos tienen 1,3% de riesgo de morir por cáncer de mama independiente del nivel socioeconómico, educacional y del sexo. Conclusión: Existen diferencias estadísticamente significativas respecto a la mortalidad entre los niveles socioeconómicos altos y bajos y también en nivel educacional, sin embargo, al realizar los métodos de regresión se obtuvo una mayor mortalidad y mayor riesgo de morir por cáncer de mama en los niveles socioeconómicos más altos asociados a, probablemente, la menor cantidad de tamizajes y realización de mamografías en este estrato. A partir del año 2008 se observó un incremento a los niveles originales observados al inicio del segundo milenio incrementando las diferencias existentes en los índices de desigualdad tanto por nivel educacional como por nivel socioeconómico incrementando en 20 veces respecto al nivel educacional, y 1.88 respecto al nivel socioeconómico.

Introduction: Breast cancer is the leading cause of death in cancers in Chile according to Globocan 2018. Among the factors that explain this high mortality, we find a low rate of detection and performance of mammograms in high socioeconomic levels. This is why understanding the causes of death and the factors that affect mortality and fatality from breast cancer in the last 17 years will allow us to focus on public policies for the next 50 years Materials and Methods: Retrospective longitudinal cohort study in 79,996 hospital discharges and 20,220 deaths obtained from the DEIS MINSAL page, years 2001 -2016. For the univariate analysis, a Prais-Weinstein rate adjustment regression was performed according to age and sex according to the WHO rate adjustment model. For discrete type variables, they were described by percentages and rates, and median and standard deviation were used for continuous type variables. A smirnov-kolmolgorov test was performed to determine the type of distribution and normality of the samples. For dichotomous variables, a binary logistic regression model was used to describe these variables and determine the possible association between the socioeconomic and educational level of the patients diagnosed with breast cancer. Abstract: In this observational, longitudinal and retrospective study with 101.292 patients that includes men and women of all ages with diagnosis of breast cancer all along Chile, we´ll analyze the impact of socioeconomic level, evaluated through educational level and money income, into the prevalence, mortality and lethality of breast cancer in the years 2001 to 2016. Results: People with a high socioeconomic level died 1.88 times more, with a CI between 1.83 and 1.94, than those with a low socioeconomic level. On the other hand, people with a higher educational level died 0.5 times less according to the regression carried out with respect to the low educational level with a CI between 0.47 and 0.52, but the lower the educational level the mortality increased 20 times, constituting an inverse cause. Regarding sex, women died 2.08 times more than men. For the high socioeconomic level in relation to the low one an OR [1.88 (1.83 to 1.94)], p<0.0001], for the high educational level in relation to the low one it was in favor of the higher educational level with OR [0.5 (0.47 - 0.52)] and as for the comparison of sexes an OR [1.04 (1.03-2.17), p=0.039]. In other words, the difference between mortality was significant for all the intervals for sex, educational level and socioeconomic level. A constant baseline mortality of 0.013 was found, i.e., everyone has a 1.3% risk of dying from breast cancer regardless of socioeconomic level, educational level and sex. Conclusions: There are statistically significant differences in mortality between high and low socioeconomic levels and also in educational level; however, when regression methods were used, a higher mortality and higher risk of dying from breast cancer was obtained in the higher socioeconomic levels, probably associated with the lower number of screenings and mammograms performed in this stratum. As of 2008, an increase to the original levels observed at the beginning of the second millennium was observed, increasing the existing differences in the inequality indexes both by educational level and socioeconomic level, increasing by 20 times with respect to educational level, and 1.88 times with respect to socioeconomic level.

Urinary tract infection caused by Enterococcus spp.: Risk factors and mortality. An observational study.

BACKGROUND AND OBJECTIVE: Urinary tract infections (UTIs) are frequently caused by Enterococcus spp. This work aims to define the risk factors associated with UTIs caused by Enterococci and to determine its overall mortality and predictive risk factors. MATERIALS AND METHODS: A retrospective study was conducted on bacteremic UTIs caused by Enterococcus spp. among inpatients. We compared 106 inpatients with bacteremic UTIs caused by Enterococcus spp. vs. a random sample of 100 inpatients with bacteremic UTIs caused by other enterobacteria. RESULTS: A total of 106 inpatients with UTIs caused by Enterococcus spp. were analyzed, 51 of whom had concomitant positive blood cultures. Distribution by species was 83% E. faecalis and 17% E. faecium. The mean Charlson Comorbidity Index score was 5.9±2.9. Upon comparing bacteremic UTIs caused by Enterococcus spp. vs. bacteremic UTIs caused by others enterobacteria, we found the following independent predictors of bacteremic UTI by Enterococcus: male sex, obstructive uropathy, nosocomial infection, cancers of the urinary system, and previous antimicrobial treatment. Overall, inpatient mortality was 16.5% and was associated with a higher Sequential Organ Failure Assessment (SOFA) score (>4); severe comorbidities such as immunosuppression, malignant hemopathy, and nephrostomy; and Enterococcus faecium species and its pattern of resistance to ampicillin or vancomycin (p<0.05). Appropriate empiric antibiotic therapy was not associated with a better prognosis (p>0.05). CONCLUSIONS: Enterococcus spp. is a frequent cause of complicated UTI in patients with risk factors. High mortality secondary to a severe clinical condition and high comorbidity may be sufficient for justifying the implementation of empiric treatment of at-risk patients.

Design of magnetic hybrid nanostructured lipid carriers containing 1,8-cineole as delivery systems for anticancer drugs: Physicochemical and cytotoxic studies.

The development of versatile carriers to deliver chemotherapeutic agents to specific targets with establishing drug release kinetics and minimum undesirable side effects is becoming a promising relevant tool in the medical field. Magnetic hybrid nanostructured lipid carriers (NLC) were prepared by incorporation of 1,8-cineole (CN, a monoterpene with antiproliferative properties) and maghemite nanoparticles (MNPs) into a hybrid matrix composed of myristyl myristate coated with chitosan. Hybrid NLC characterized by DLS and TEM confirmed the presence of positively charged spherical nanoparticles of around 250 nm diameter and +10.2 mV of Z-potential. CN encapsulation into the lipid core was greater than 75 % and effectively released in 24 h. Modification of the crystalline structure of nanoparticles after incorporation of CN and MNPs was observed by XRD, DSC, and TGA analyses. Superparamagnetic NLC behavior was verified by recording the magnetization using a vibrating scanning magnetometer. NLC resulted in more cytotoxic than free CN in HepG2 and A549 cell lines. Particularly, viability inhibition of HepG2 and A549 cells was increased from 35 % to 55 % and from 38 % to 61 %, respectively, when 8 mM CN was incorporated into the lipid NPs at 24 h. Green fluorescent-labeled NLC with DIOC18 showed an enhanced cellular uptake with chitosan-coated NLC. Besides, no cytotoxicity of the formulations in normal WI-38 cells was observed, suggesting that the developed hybrid NLC system is a safe and good potential candidate for the selective delivery and potentiation of anticancer drugs.

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.

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.

A laboratory study of root canal and isthmus disinfection in extracted teeth using various activation methods with a mixture of sodium hypochlorite and etidronic acid.

AIM: To evaluate in a laboratory setting the antibiofilm activity of several irrigating protocols including conventional irrigation, ultrasonic activation and XP-endo Finisher, with a mixture of sodium hypochlorite and etidronic acid in infected isthmuses and root canals of extracted human mandibular molar teeth. METHODOLOGY: Fifty-six mesial roots of mandibular molars, half of them with a continuous isthmus from the cervical to the apical third between the two root canals (type 1), and the other half with a continuous isthmus from the cervical to the middle third and one canal in the apical third (type 2), were included. The root canals were contaminated for 7 days with an Enterococcus faecalis suspension. There were three experimental groups plus a control group (n = 7 per type of root canal anatomy). All the root canals, except for the control group that was not treated, were chemomechanically prepared and then assigned to one of the experimental groups according to the final adjunctive procedure: conventional irrigation, ultrasonic activation or XP-endo Finisher activation. The irrigating solution used was a combination of 2.5% sodium hypochlorite and 9% etidronic acid, and the final protocols were applied for three cycles of 30 s with a 3 mL volume. The antibiofilm activity was evaluated at each location (root canal and isthmus) and third (cervical, middle and apical) using confocal laser scanning microscopy and the live/dead technique. Statistical analysis was performed using SPSS (descriptive statistics) and SUDAAN (P-value calculations). RESULTS: Root canals had significantly lower biovolume values than the isthmuses (P < 0.05). The biovolume in the root canals was significantly reduced in all the experimental groups in all the thirds except for conventional irrigation in the apical third (P > 0.05). In the cervical and middle thirds, ultrasonic activation was associated with the lowest biovolumes (P < 0.05), followed by XP-endo Finisher. In the isthmus, disinfection was similar in all the thirds for all the protocols. Conventional irrigation was associated with intermediate values with no significant differences from the control group or from the activated protocols (P > 0.05), although the latter were significantly different from the control group (P < 0.05). No differences were found between ultrasonic activation and XP-endo Finisher in the middle and apical thirds (P > 0.05) in the isthmuses. CONCLUSIONS: In this laboratory study on extracted teeth, the isthmus was more difficult to disinfect than root canals. In the root canals, ultrasonic activation and XP-endo Finisher had a greater effectiveness than conventional irrigation. In the isthmuses, no differences were observed between the two activation techniques and conventional irrigation.

A Molecular Stratification of Chilean Gastric Cancer Patients with Potential Clinical Applicability.

Gastric cancer (GC) is a complex and heterogeneous disease. In recent decades, The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) defined GC molecular subtypes. Unfortunately, these systems require high-cost and complex techniques and consequently their impact in the clinic has remained limited. Additionally, most of these studies are based on European, Asian, or North American GC cohorts. Herein, we report a molecular classification of Chilean GC patients into five subtypes, based on immunohistochemical (IHC) and in situ hybridization (ISH) methods. These were Epstein-Barr virus positive (EBV+), mismatch repair-deficient (MMR-D), epithelial to mesenchymal transition (EMT)-like, and accumulated (p53+) or undetected p53 (p53-). Given its lower costs this system has the potential for clinical applicability. Our results confirm relevant molecular alterations previously reported by TCGA and ACRG. We confirm EBV+ and MMR-D patients had the best prognosis and could be candidates for immunotherapy. Conversely, EMT-like displayed the poorest prognosis; our data suggest FGFR2 or KRAS could serve as potential actionable targets for these patients. Finally, we propose a low-cost step-by-step stratification system for GC patients. To the best of our knowledge, this is the first Latin American report on a molecular classification for GC. Pending further validation, this stratification system could be implemented into the routine clinic.

First-line endocrine therapy for advanced breast cancer. A real-world study at a Latin American university health institution.

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.