Angiogenesis is promoted by hypoxic cervical carcinoma-derived extracellular vesicles depending on the endothelial cell environment.

INTRODUCTION: Cancer needs perfusion for its growth and metastasis. Cancer cell-derived extracellular vesicles (CA-EVs) alter the tumor microenvironment (TME), potentially promoting angiogenesis. We hypothesize that conditions in the tumor, e.g., hypoxia, and in the target cells of the TME, e.g., nutrient deprivation or extracellular matrix, can affect the angiogenic potential of CA-EVs, which would contribute to explaining the regulation of tumor vascularization and its influence on cancer growth and metastasis. METHODS: CA-EVs were isolated and characterized from cervical carcinoma cell lines HeLa and SiHa cultured under normoxia and hypoxia, and their angiogenic potential was evaluated in vitro in three endothelial cells (ECs) lines and aortic rings, cultured in basal (growth factor-reduced) or complete medium. RESULTS: Hypoxia increased EV production 10-100 times and protein content 2-4 times compared to normoxic CA-EVs. HeLa-EVs contained six times more RNA than SiHa-EVs, and this concentration was not affected by hypoxia. Treatment with CA-EVs increased tube formation and sprouting in ECs and aortic rings cultured in basal medium and long-term stabilized the stablished vascular networks formed by ECs cultured in complete medium. CONCLUSION: Hypoxia differentially affects CA-EVs in a cell line-dependent manner. The cellular environment (nutrient availability and extracellular matrix scaffold) influences the effect of CA-EV on the angiogenic potential of ECs.

Analysis of oncological drugs authorised in Spain in the last decade: association between clinical benefit and reimbursement.

BACKGROUND: Our study aimed to assess whether there was a relationship between clinical benefits and reimbursement decisions as well as the inclusion of economic evaluations in  therapeutic positioning reports (IPTs) and to explore factors influencing reimbursement decisions. MATERIALS AND METHODS: We analysed all anti-cancer drugs approved in Spain from 2010 to September 2022. The clinical benefit of each drug were evaluated using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) 1.1. The characteristics of these drugs were obtained from the Spanish Agency of Medicines and Medical Devices. Reimbursement status information was obtained using BIFIMED, a web resource available in Spanish and consulted the agreements of the Interministerial Committee on Pricing of Medicines (CIPM). RESULTS: In total, 73 drugs were included involving 197 indications. Almost half of the indications had substantial clinical benefit (49.8% yes vs. 50.3% no). Of the 153 indications with a reimbursement decision, 61 (56.5%) reimbursed indications had substantial clinical benefit compared to 14 (31.1%) of the non-reimbursed (p < 0.01). The median gain of overall survival was 4.9 months (2.8-11.2) for reimbursed indications and 2.9 months (1.7-5) in non-reimbursed (p < 0.05). Only six (3%) indications had an economic evaluation in the IPT. CONCLUSION: Our study revealed that there is a relationship between substantial clinical benefit and the reimbursement decision in Spain. However, we also found that the overall survival gain was modest, and a significant proportion of the reimbursed indications had no substantial clinical benefit. Economic evaluations in IPTs are infrequent and cost-effectiveness analysis is not provided by CIPM.

Diagnostic accuracy of lumbar CT and MRI in the evaluation of chronic low back pain without red flag symptoms.

BACKGROUND: Low back pain (LBP) is one of the most frequent reasons for medical consultation. Most of the patients will have nonspecific LBP, which usually are self-limited episodes. It is unclear which of the diagnostic imaging pathways is most effective and costeffective and how the imaging impacts on patient treatment. Imaging techniques are usually indicated if symptoms remain after 6 weeks. Magnetic resonance imaging (MRI) is the diagnostic imaging examination of choice in lumbar spine evaluation of low back pain; however, availability of MRI is limited. OBJECTIVES: To evaluate the diagnostic accuracy of computed tomography (CT) with MRI (as standard of reference) in the evaluation of chronic low back pain (LBP) without red flags symptoms. To compare the results obtained by two radiologists with different grades of experience. MATERIALS AND METHODS: Patients with chronic low back pain without red flags symptoms were retrospectively reviewed by two observers with different level of experience. Patients included had undergone a lumbar or abdominal CT and an MRI within a year. Once the radiological information was collected, it was then statistically reviewed. The aim of the statistical analysis is to identify the equivalence between both diagnostic techniques. To this end, sensitivity, specificity and validity index were calculated. In addition, intra and inter-observer reliability were measured by Cohen's kappa values and also using the McNemar test. RESULTS: 340 lumbar levels were evaluated from 68 adult patients with chronic low back pain or sciatica. 63.2% of them were women, with an average age of 60.3 years (SD 14.7). CT shows high values of sensitivity and specificity (>80%) in most of the items evaluated, but sensitivity was low for the evaluation of density of the disc (40%) and for the detection of disc herniation (55%). Moreover, agreement between MRI and CT in most of these items was substantial or almost perfect (Cohen's kappa-coefficient > 0'8), excluding Modic changes (kappa = 0.497), degenerative changes (kappa0.688), signal of the disc (kappa = 0.327) and disc herniation (kappa = 0.639). Finally, agreement between both observers is mostly high (kappa > 0.8). Foraminal stenosis, canal stenosis and the grade of the canal stenosis were overdiagnosed by the inexperienced observer in the evaluation of CT images. CONCLUSIONS AND SIGNIFICANCE: CT is as sensitive as lumbar MRI in the evaluation of most of the items analysed, excluding Modic changes, degenerative changes, signal of the disc and disc herniation. In addition, these results are obtained regardless the experience of the radiologist. The rising use of diagnostic medical imaging and the improvement of image quality brings the opportunity of making a second look of abdominal CT in search of causes of LBP. Thereby, inappropriate medical imaging could be avoided (2). In addition, it would allow to reduce MRI waiting list and prioritize other patients with more severe pathology than LBP.

Evaluation of rectus abdominis muscle strength and width of hernia defect in patients undergoing incisional hernia surgery.

BACKGROUND: The aim of this study was to analyze the strength status of the rectus abdominis muscle in patients with incisional hernia and the relationship between the width of the hernia defect and the strength of the rectus abdominis muscle. METHODS: This is a observational cohort study of patients with medial line incisional hernia (July-October 2022), classified as W2 according to the European Hernia Society (EHS). The data collected were demographic and clinical characteristics related to hernia, and measure of the rectus abdominis muscle strength using an isokinetic dynamometer and a strain gauge. We analyzed the relationship between hernia width and rectus abdominis muscle strength with correlation tests to adjustment by age, sex, BMI, and body composition. RESULTS: A total of 40 patients (64% female) with a mean age of 57.62 years (SD 11) were enrolled in the study. The mean BMI was 29.18 (SD 5.06), with a mean percentage of fat mass of 37.8% (SD 8.47) and a mean percentage of muscle mass of 60.33% (SD 6.43). The maximum width of the hernia defect was 6.59 cm (SD 1.54). In the male group, the mean bending force moment (ISOK_PT) was 94.01 Nw m (SD 34.58), bending force moment relative to body weight (ISOK_PT_Weight) was 103.32 Nw m (SD 37.48), and peak force (PK_90) was 184.71 N (SD 47.01). In the female group, these values were 58.11 Nw m (SD 29.41), 66.48 Nw m (SD 32.44), and 152.50 N (SD 48.49), respectively. Statistically significant differences were observed in the relationship between the data obtained with the isokinetic dynamometer and sex (p = 0.002), as well as between the data obtained with the isokinetic dynamometer and age (p = 0.006). Patients in the 90th percentile (P90) of rectus abdominis muscle strength also had smaller hernia defect widths (p = 0.048). CONCLUSIONS: In this study, age and sex were identified as the most statistically significant predictor variables for rectus abdominis muscle strength. The width of the hernia defect exhibited a trend towards statistical significance.

Vertebral osteomyelitis after spine instrumentation surgery: risk factors and management.

BACKGROUND: Vertebral osteomyelitis after spine instrumentation surgery (pVOM) is a rare complication. Most cases of infection occur early after surgery that involve skin and soft tissue and can be managed with debridement, antibiotics, and implant retention (DAIR). AIM: To identify pVOM risk factors and evaluate management strategies. METHODS: From a multicentre cohort of deep infection after spine instrumentation (IASI) cases (2010-2016), pVOM cases were compared with those without vertebral involvement. Early and late infections were defined (<60 days and >60 days after surgery, respectively). Multivariate analysis was used to explore risk factors. FINDINGS: Among 410 IASI cases, 19 (4.6%) presented with pVOM, ranging from 2% (7/347) in early to 19.1% (12/63) in late IASIs. After multivariate analysis, age (adjusted odds ratio (aOR): 1.10; 95% confidence interval (CI): 1.03-1.18), interbody fusion (aOR: 6.96; 95% CI: 2-24.18) and coagulase-negative staphylococci (CoNS) infection (aOR: 3.83; 95% CI: 1.01-14.53) remained independent risk factors for pVOM. Cases with pVOM had worse prognoses than those without (failure rate; 26.3% vs 10.8%; P = 0.038). Material removal was the preferred strategy (57.9%), mainly in early cases, without better outcomes (failure rate; 33.3% vs 50% compared with DAIR). Late cases managed with removal had greater success compared with DAIR (failure rate; 0% vs 40%; P = 0.067). CONCLUSION: Risk factors for pVOM are old age, use of interbody fusion devices and CoNS aetiology. Although the diagnosis leads to a worse prognosis, material withdrawn should be reserved for late cases or when spinal fusion is achieved.

Cáncer de mama Her2-positivo: Terapias sistémicas actuales y experiencia local

El cáncer de mama (CM) es la primera causa de muerte por cáncer en mujeres tanto a nivel mundial como en Chile. Basados en características clínicas, histológicas y moleculares, múltiples estudios han identificado cuatro subtipos básicos de CM, los cuales están asociados a estrategias de tratamiento específicas y diferenciadas. El CM HER2-positivo representa un 15%-25% de todas las neoplasias mamarias y se caracteriza por su agresividad, recurrencia temprana y mayor tendencia a presentar compromiso del sistema nervioso central. En las últimas décadas, nuevas terapias dirigidas se han posicionado como el estándar de tratamiento y han cambiado la historia natural de esta enfermedad, transformándola en una enfermedad potencialmente curable incluso en etapas avanzadas. Esta revisión busca entregar un resumen de las bases biológicas de esta enfermedad. Por otro lado, dada la aparición de un creciente número de nuevas estrategias de manejo sistémico, nos proponemos revisar sus mecanismos de acción analizando reportes de datos clínicos publicados y la experiencia de nuestro grupo.

Breast cancer (BC) is the leading cause of cancer death for women both worldwide and in Chile. Based on clinical, histological, and molecular features, studies have identified four BC subtypes that correlate with treatment sensitivity. Human Epidermal growth factor Receptor type 2-positive (HER2+) BC represents 15%-25% of newly diagnosed breast neoplasms; HER2+ BC is characterized by its aggressive behavior, early recurrence, and higher risk of brain metastasis. In recent years, HER2-targeted therapies have become the mainstay of treatment and have redefined the natural history of this subtype, reducing relapse rates for early-stage patients and increasing survival in advanced-stage patients. Herein we review novel treatment strategies and their mechanisms of action, along with clinical and real-world data. We also provide a summary of currently available treatments for this subtype and our local experience regarding the management of this disease.

Impact of the use of antibiotics on the clinical response to immune checkpoint inhibitors in patients with non-small cell lung cancer.

OBJECTIVE: Recent research suggests that the use of antibiotics could reduce the efficacy of checkpoint inhibitors, in addition to other well-known factors. It could be due to gut microbiota modification, which impact over the immune system response. However, the information available so far is contradictory. The objective of this research was to clarify whether antibiotic use influences efficacy of checkpoint inhibitors treatments in non-small cell lung cancer patients in clinical practice. METHODS: Therefore, a retrospective observational study was designed. Use of antibiotics among patients treated with atezolizumab, pembrolizumab or nivolumab was assessed within 2 months of checkpoint inhibitors treatments initiation. RESULTS: A total of 140 patients were included, mostly men, with good performance status (ECOG 0-1), all of them previously treated with chemotherapy. An antibiotic prescription was identified in 31% of these patients, mainly fluoroquinolones or beta-lactams. The most frequent indication was respiratory infection. Both progression-free survival and overall survival were lower for patients treated with anti-infective drugs, although this difference was not statistically significant. CONCLUSIONS: More studies are needed to draw conclusions about the impact of antibiotics on the efficacy of immunotherapy.

Lesser-Consumed Tropical Fruits and Their by-Products: Phytochemical Content and Their Antioxidant and Anti-Inflammatory Potential.

Açaí, lychee, mamey, passion fruit and jackfruit are some lesser-consumed tropical fruits due to their low commercial production. In 2018, approximately 6.8 million tons of these fruits were harvested, representing about 6.35% of the total world production of tropical fruits. The present work reviews the nutritional content, profile of bioactive compounds, antioxidant and anti-inflammatory capacity of these fruits and their by-products, and their ability to modulate oxidative stress due to the content of phenolic compounds, carotenoids and dietary fiber. Açaí pulp is an excellent source of anthocyanins (587 mg cyanidin-3-glucoside equivalents/100 g dry weight, dw), mamey pulp is rich in carotenoids (36.12 mg ß-carotene/100 g fresh weight, fw), passion fruit peel is rich in dietary fiber (61.16 g/100 dw). At the same time, jackfruit contains unique compounds such as moracin C, artocarpesin, norartocarpetin and oxyresveratrol. These molecules play an important role in the regulation of inflammation via activation of mitogen-activated protein kinases (including p38, ERK and JNK) and nuclear factor κB pathways. The properties of the bioactive compounds found in these fruits make them a good source for use as food ingredients for nutritional purposes or alternative therapies. Research is needed to confirm their health benefits that can increase their marketability, which can benefit the primary producers, processing industries (particularly smaller ones) and the final consumer, while an integral use of their by-products will allow their incorporation into the circular bioeconomy.

Could thymoglobulin increase hemorrhagic risk in the perioperative transplantation period of sensitized kidney recipients?

OBJECTIVE: It has been described that thymoglobulin could increase the risk of infections and malignancies, in comparison to basiliximab. Leukopenia and thrombocytopenia are also more common within the first days after transplantation among thymoglobulin patients. Our objective was to analyze bleeding complications in this subset of patients. MATERIAL AND METHODS: Bleeding complications were evaluated among 515 renal transplants carried out at our institution between 2012 and 2018. We compared patients treated with thymoglobulin (Group 1, N=91) with those treated with basiliximab (Group 2, N=424). RESULTS: We found differences in platelet decrease: 95,142.2 (55,339.6) in Group 1 and 52,364.3 (69,116.6) in Group 2 (P=0.001), number of patients with severe thrombocytopenia (<75,000/mm3) (20.8% vs. 3.7%, P=0.001), number of blood units transfused (3.25 (0.572) vs. 2.2 (0.191, P=0.028) and percentage of patients that required surgery due to bleeding (18.2% vs. 7.7%, P=0.046). In a multiple lineal regression multivariable analysis (dependent variable was number of blood units transfused), only age [OR 0.037, 95% CI (0.003-0.070)] and type of immunosuppression [OR 1.592, 95% CI (1.38-2.84)] showed statistical significance. CONCLUSIONS: The use of thymoglobulin in the perioperative transplantation period could increase bleeding complications. In our series, in the group of patients with thymoglobulin, severe thrombocytopenia was 6 times more frequent, and active bleeding that required surgery was also 2.5 times more frequent. One way to continue with the use of this immunosuppression agent, might be to adjust the dose instead of discontinuing it. The use of thymoglobulin should be a factor to consider in the postoperative period of these patients.

Radioguided surgery with iodine-125 seeds in breast cancer patients treated with neoadjuvant chemotherapy.

OBJECTIVE: To evaluate the use of radioactive iodine-125 seed (RIS) in breast and/or axillary surgery, in patients with breast cancer treated with neoadjuvant chemotherapy (NAC). MATERIAL AND METHODS: Prospective study between January 2016 and June 2020. 80 women T1-3,N0-2,M0: 30 RIS marking the breast tumor, 36 both the tumor and the biopsied positive axillary node, and 14 only the axilla. Age: 54.7 ±â€¯11.4 years. Tumor size: 34.1 ±â€¯14.6 mm. Histological type: invasive ductal carcinoma 90.0%. Molecular subtypes: luminal-A 23.8%, luminal-B/HER2- 33.7%, luminal-B/HER2+ 18.8%, HER2+ 7.5%, basal-like 16,2%. RESULTS: Of the 66 patients with RIS marking of the tumor (51 pre-NAC, 15 post-NAC), 92.1% had tumor-free surgical margins, with a specimen volume of 126.7 ±â€¯111.2 cm3. Of the 5 s local excisions, in 3 the resection margin was involved (1 mastectomy). Of the 50 patients N1 with RIS marking (MLN), 44 pre-NAC and 6 post-NAC, MLN was identified in 97.2%: negative 23, positive 26. In 45/50 patients, sentinel node biopsy (SNB) was performed and it was identified in 93.3%: negative 26, positive 16. In 1 case RIS was not placed correctly and SNB was not identified due to non-migration. In 61.9% of the patients, MLN was among the SNB identified in the surgery. In 5 patients with mismatched SNB and MLN, the pathological result of the SNB was negative and the MLN was positive. Axillary lymph node dissection was performed in 53.8% of the patients. CONCLUSION: RIS allow to perform breast-conserving surgery and improve detection of residual axillary disease in patients treated with NAC.

Adaptación transcultural de la versión colombiana de la Escala de Soledad de UCLA en pacientes con diagnóstico de cáncer / Transcultural adaptation of the Colombian version of the UCLA Loneliness Scale in patients diagnosed with cancer

Resumen Introducción: La soledad no deseada es un constructo que se ha relacionado con desenlaces negativos en diferentes aspectos de la salud, incluidos aquellos de los pacientes con cáncer. La escala de soledad de UCLA es un instrumento ampliamente utilizado en el contexto de investigación en salud para medir dicho constructo, y en Colombia la versión 03 de dicho instrumento no se encuentra traducida, ni adaptada transculturalmente. Objetivo: Traducir y adaptar transculturalmente la escala de soledad de UCLA, versión 03 para su uso en pacientes con cáncer en Colombia. Métodos: El proceso de traducción y adaptación transcultural siguió la metodología propuesta por el grupo EORTC, con el objetivo de lograr la equivalencia semántica con la versión original de la escala disponible en inglés. Se realizó una prueba piloto con 20 pacientes colombianos diagnosticados con diferentes tipos de cáncer, que asistieron al Instituto Nacional de Cancerología de Colombia. Resultados: No hubo cambios ni en la traducción de instrucciones ni en las opciones de respuesta. En la versión conciliada se modificó el ítem UC1. En la prueba piloto, dos de 20 pacientes informaron que los ítems UC6, UC7, UC11 y UC19 deberían ser modificados y un paciente mencionó que el ítem UC8 era difícil de entender; sin embargo, no se hicieron cambios dado el bajo número de pacientes que reportaron estos hallazgos, y las sugerencias planteadas podían cambiar el sentido y la equivalencia de los ítems de la escala original. Ninguno de los ítems fue ofensivo para los pacientes. Conclusión: Se generó una versión traducida y adaptada transculturalmente para ser validada en pacientes con cáncer en Colombia.

Abstract Introduction: Unwanted loneliness is a construct that has shown relationships with different negative outcomes of health, including those of patients with cancer. In the context of health research, the UCLA loneliness scale is a widely used instrument for measuring this construct. In Colombia, the 03 version of this instrument has still not been neither translated, nor transculturally adapted. Objective: To translate and perform transcultural adaptation of the UCLA loneliness scale, version 03 for its use in patients having cancer in Colombia. Methods: The process of translation and transcultural adaptation followed the methodology proposed by the EORTC group, aimed at achieving semantic equivalence with the original version of the scale. A pilot test has been made with 20 Colombian patients diagnosed with different types of cancer, attending the Instituto Nacional de Cancerología, Colombia. Results: In the reconciliated version, item UC1 has been modified. There has been not changes neither in translation of instructions, nor in response options. In pilot testing two out of 20 patients reported that items UC6, UC7, UC11 y UC19 should be modified and one patient mentioned that item UC8 was difficult to understand; however, no changes were made taking into account the low number of patients describing similar findings, and because these suggestions could change the semantic equivalence of these items. No items were deemed offensive. Conclusion: It is available a transculturally adapted version of the UCLA loneliness scale, version 03 for its validation in patients with cancer in Colombia.

Effects of mesenchymal stem cell culture on radio sterilized human amnion or radio sterilized pig skin in burn wound healing.

Deep second and third degree burns treatment requires fibroblasts, keratinocytes and other skin cells in order to grow new dermis and epidermis. Cells can proliferate, secrete growth factors and extracellular matrix required to repair the damaged tissue. Radiosterilized human amnion and radiosterilized pig skin have been used as natural origin skin dressings for burned patients. Adipose-derived mesenchymal stem cells can differentiate into fibroblasts and keratinocytes and improve wound-healing progress. These cells can stimulate vascular tissue formation, release growth factors, synthetize new extracellular matrix and immunoregulate other cells. In this study, we developed mesenchymal stem cells-cellularized skin substitutes based from radiosterilized human amnion or pig skin. Third-degree burns were induced in mice animal models to evaluate the effect of cellularized skin substitutes on burn wound healing. Mesenchymal phenotype was immunophenotypically confirmed by flow cytometry and cell viability was close to 100%. Skin recovery was evaluated in burned mice after seven and fourteen days post-coverage with cellularized and non-cellularized sustitutes. Histological techniques and immunofluorescence were used to evaluate re-epithelization and type I collagen deposition. We determined that cellularized-human amnion or cellularized-pig skin in combination with mesenchymal stem cells improve extracellular matrix deposition. Both cellularized constructs increase detection of type I collagen in newly formed mouse skin and can be potentially used as skin coverage for further clinical treatment of burned patients.

Nuclear Charge Radii of the Nickel Isotopes

Collinear laser spectroscopy is performed on the nickel isotopes ^{58-68,70}Ni, using a time-resolved photon counting system. From the measured isotope shifts, nuclear charge radii R_{c} are extracted and compared to theoretical results. Three ab initio approaches all employ, among others, the chiral interaction NNLO_{sat}, which allows an assessment of their accuracy. We find agreement with experiment in differential radii δ⟨r_{c}^{2}⟩ for all employed ab initio methods and interactions, while the absolute radii are consistent with data only for NNLO_{sat}. Within nuclear density functional theory, the Skyrme functional SV-min matches experiment more closely than the Fayans functional Fy(Δr,HFB).

Genomic landscape and immune-related gene expression profiling of epithelial ovarian cancer after neoadjuvant chemotherapy.

Platinum-based neoadjuvant chemotherapy followed by interval debulking surgery is an accepted treatment for patients with stage III or IV epithelial ovarian cancer who are not suitable for primary debulking surgery. The identification of suitable adjuvant treatments in these patients is an unmet need. Here, we explore potential genomic characteristics (mutational and immune-associated expression profiles) in a series of patients undergoing neoadjuvant chemotherapy. Tumor samples from biopsy and interval debulking surgery were analyzed for mutational landscape and immune profiling, together with detailed immunohistochemistry using different immune cell markers, and correlated with clinicopathological characteristics and potential response to neoadjuvant chemotherapy. No major differences in the mutational landscape were observed in paired biopsy and surgery samples. Genomic loss of heterozygosity was found to be higher in patients with total/near-total tumor response. The immune gene expression profile after neoadjuvant chemotherapy revealed activation of several immune regulation-related pathways in patients with no/minimal or partial response. In parallel, neoadjuvant therapy caused a significant increase of tumor-infiltrating lymphocyte population abundance, primarily due to an augmentation of the CD8+ T cell population. Remarkably, these changes occurred irrespective of potential homologous recombination defects, such as those associated with BRCA1/2 mutations. Our study strengthens the use of loss of heterozygosity as a biomarker of homologous repair deficiency. The changes of immune states during neoadjuvant chemotherapy reveal the dynamic nature of tumor-host immune interactions and suggest the potential use of immune checkpoint inhibitors or their combination with poly-ADP polymerase inhibitors in high stage and grade epithelial ovarian cancer patients undergoing neoadjuvant therapy.

Prevalence of primary eosinophilic colitis in patients with chronic diarrhea and diarrhea-predominant irritable bowel syndrome.

INTRODUCTION: Primary eosinophilic colitis (PEC) is an inflammatory disease caused by the infiltration of eosinophils into the mucosa of the colon, determined after having ruled out other possible causes. It is characterized by abdominal pain and diarrhea and its prevalence is unknown. AIMS: To know the prevalence of PEC in patients with chronic diarrhea and in those with clinical criteria for diarrhea-predominant irritable bowel syndrome (IBS-D). PATIENTS AND METHODS: All patients with chronic noninflammatory diarrhea that were consecutively seen over a decade were studied through colonoscopy, with systematic biopsy. Patients with a known or decompensated organic disease, alarm features, abnormal minimal laboratory test results, and factors associated with eosinophilia were excluded. Patients with the clinical criteria for IBS-D (Rome III) were selected from the general group. Eosinophilic colitis was defined as the presence of > 35 eosinophils/100 epithelial cells per field in any of the segments. RESULTS: From the 683 patients seen, a total of 545 patients (361 women) were included in the study. Twenty-two cases of PEC were detected, resulting in a prevalence of 4.0%. A total of 343 patients had IBS-D criteria (223 women), with 16 cases of PEC detected, for a prevalence of 4.7%. Colonoscopy was normal, or almost normal, in all the PEC cases detected. CONCLUSIONS: The prevalence of PEC was 4.0% in the patients with chronic diarrhea and 4.7% in the patients with IBS-D. Peripheral eosinophilia appeared to be the main distinctive clinical characteristic, but systematic biopsy was essential for making the diagnosis.

Effects of free-fatty-acid content and saturation degree of the dietary oil sources on lipid-class content and fatty-acid digestibility along the gastrointestinal tract in broilers from 22 to 37 days of age.

The aim of the present study is to assess the effect of the free-fatty-acid (FFA) content and saturation degree of dietary fat (added at 6%) on the fatty-acid (FA) digestibility and lipid-class content along the gastrointestinal tract and excreta in broilers from 22 to 37 d of age. This is essential to determine the potential use of acid oils (refining by-products rich in FFA) in broiler diets as an alternative to crude oils. The study consisted of a 2 × 4 factorial arrangement, which included 2 fat sources (soybean oils - unsaturated, or palm oils - saturated) and 4 levels of FFA (5, 15, 35, and 50%). Samples of digestive content of the gizzard, duodenum, jejunum, ileum and of the excreta were obtained at 37 d of age. Irrespective of the dietary fat source, more than 80% of total FA (TFA) was absorbed in the jejunum. Broilers fed with unsaturated diets had a higher absorption efficiency of FA than did those fed with saturated diets. This conclusion is supported by the lower FFA content and the higher TFA and polyunsaturated FA (PUFA) digestibility coefficients in the ileum (P < 0.001) observed in the former group. The dietary FFA level did not affect the FA absorption process as much as the dietary fat source did. This was supported by the lack of statistical differences among the diets with a similar saturation degree but rather different levels of FFA, for TFA, saturated FA, and PUFA digestibility coefficients both in the jejunum and ileum. However, the interactions reported in the ileum for triacylglycerol and diacylglycerol contents (P < 0.001), as well as for monounsaturated FA digestibility coefficients (P < 0.05) show that the dietary FFA content affects the FA absorption process. The present results show that the inclusion of acid oils in grower-finisher broiler diets with FFA levels up to 35% does not have a negative impact on the FA absorption process.

Glycine rich segments adopt polyproline II helices: Implications for biomolecular condensate formation.

Many intrinsically disordered proteins contain Gly-rich regions which are generally assumed to be disordered. Such regions often form biomolecular condensates which play essential roles in organizing cellular processes. However, the bases of their formation and stability are still not completely understood. Based on NMR studies of the Gly-rich H. harveyi "snow flea" antifreeze protein, we recently proposed that Gly-rich sequences, such as the third "RGG" region of Fused in Sarcoma (FUS) protein, may adopt polyproline II helices whose association might stabilize condensates. Here, this hypothesis is tested with a polypeptide corresponding to the third RGG region of FUS. NMR spectroscopy and molecular dynamics simulations suggest that significant populations of polyproline II helix are present. These findings are corroborated in a model peptide Ac-RGGYGGRGGWGGRGGY-NH2, where a peak characteristic of polyproline II helix is observed using CD spectroscopy. Its intensity suggests a polyproline II population of 40%. This result is supported by data from FTIR and NMR spectroscopies. In the latter, NOE correlations are observed between the Tyr and Arg, and Arg and Trp side chain hydrogens, confirming that side chains spaced three residues apart are close in space. Taken together, the data are consistent with a polyproline II helix, which is bent to optimize interactions between guanidinium and aromatic moieties, in equilibrium with a statistical coil ensemble. These results lend credence to the hypothesis that Gly-rich segments of disordered proteins may form polyproline II helices which help stabilize biomolecular condensates.

Radioguided surgery with iodine-125 seeds in breast cancer patients treated with neoadjuvant chemotherapy. / Cirugía radioguiada con semillas de yodo-125 en pacientes con cáncer de mama tratadas con quimioterapia neoadyuvante.

OBJECTIVE: To evaluate the use of radioactive iodine-125 seed (RIS) in breast and/or axillary surgery, in patients with breast cancer treated with neoadjuvant chemotherapy (NAC). MATERIAL AND METHODS: Prospective study between January 2016 and June 2020. 80 women T1-3,N0-2,M0: 30 RIS marking the breast tumor, 36 both the tumor and the biopsied positive axillary node, and 14 only the axilla. Age: 54.7±11.4 years. Tumor size: 34.1±14.6mm. Histological type: invasive ductal carcinoma 90.0%. Molecular subtypes: luminal-A 23.8%, luminal-B/HER2- 33.7%, luminal-B/HER2+ 18.8%, HER2+ 7.5%, basal-like 16,2%. RESULTS: Of the 66 patients with RIS marking of the tumor (51 pre-NAC, 15 post-NAC), 92.1% had tumor-free surgical margins, with a specimen volume of 126.7±111.2 cm3. Of the 5 second local excisions, in 3 the resection margin was involved (1 mastectomy). Of the 50 patients N1 with RIS marking (MLN), 44 pre-NAC and 6 post-NAC, MLN was identified in 97.2%: negative 23, positive 26. In 45/50 patients, sentinel node biopsy (SNB) was performed and it was identified in 93.3%: negative 26, positive 16. In 1 case RIS was not placed correctly and SNB was not identified due to non-migration. In 61.9% of the patients, MLN was among the SNB identified in the surgery. In 5 patients with mismatched SNB and MLN, the pathological result of the SNB was negative and the MLN was positive. Axillary lymph node dissection was performed in 53.8% of the patients. CONCLUSION: RIS allow to perform breast-conserving surgery and improve detection of residual axillary disease in patients treated with NAC.

Cáncer de mama triple negativo: terapias sistémicas actuales y experiencia local / Triple negative breast cancer: current systemic therapy and local experience

Resumen El cáncer de mama (CM) es la principal causa de muerte por cáncer en mujeres chilenas. Es una enfermedad heterogénea, en la cual se han identificado cuatro subtipos básicos, determinados según características clínicas, histológicas y moleculares, los que se relacionan a estrategias terapéuticas. El CM triple negativo (CMTN) se caracteriza por su agresividad, recaída temprana y mayor tendencia a presentarse en etapas avanzadas. Frecuentemente afecta a mujeres jóvenes o con antecedentes familiares de CM u ovario. La única terapia sistémica aprobada para el CMTN es la quimioterapia; sin embargo, recientemente terapias moleculares con inhibidores de puntos de control inmune e inhibidores de la poli-adenosina difosfato ribosa polimerasa, han mostrado eficacia en pacientes seleccionados, y se han agregado al arsenal terapéutico para CMTN. Dada la aparición de estas nuevas estrategias, parece relevante entender la heterogeneidad de esta enfermedad, los mecanismos de acción de las nuevas terapias, resultados clínicos y criterios de selección de pacientes para terapias moleculares. Presentamos una revisión de la terapia sistémica actual del CMTN.

Breast cancer is the leading cause of cancer death in Chilean women and worldwide. It is a heterogeneous disease and four different subtypes have been identified based on clinical, histological and molecular features, which correlate with different treatment tumor sensitivity. Triple negative breast cancer is characterized by its aggressiveness, early relapse, and a greater tendency to present in advanced stages. It frequently affects young women, with cancer family history, especially breast or ovarian cancer. The approved systemic therapy for triple negative breast cancer is chemotherapy; however, recently, targeted therapies with checkpoint inhibitors and polyadenosine diphosphate ribose polymerase inhibitors have been shown to be effective in selected patients and have been added to the therapeutic arsenal for triple negative breast cancer. Given the appearance of these new strategies, it seems relevant to understand the heterogeneity of this disease, the mechanisms of action behind new therapies, clinical results, and the criteria to select patients for molecular therapies. We present a review of the current systemic therapy of this breast cancer subtype.