LBDNet interlaboratory comparison for the dicentric chromosome assay by digitized image analysis applying weighted robust statistical methods.

PURPOSE: This interlaboratory comparison was conducted to evaluate the performance of the Latin-American Biodosimetry Network (LBDNet) in analyzing digitized images for scoring dicentric chromosomes from in vitro irradiated blood samples. The exercise also assessed the use of weighted robust algorithms to compensate the uneven expertise among the participating laboratories. METHODS: Three sets of coded images obtained through the dicentric chromosome assay from blood samples irradiated at 1.5 Gy (sample A) and 4 Gy (sample B), as well as a non-irradiated whole blood sample (sample C), were shared among LBDNet laboratories. The images were captured using the Metafer4 platform coupled with the AutoCapt module. The laboratories were requested to perform triage scoring, conventional scoring, and dose estimation. The dose estimation was carried out using either their laboratory calibration curve or a common calibration curve. A comparative statistical analysis was conducted using a weighted robust Hampel algorithm and z score to compensate for uneven expertise in dicentric analysis and dose assessment among all laboratories. RESULTS: Out of twelve laboratories, one had unsatisfactory estimated doses at 0 Gy, and two had unsatisfactory estimated doses at 1.5 Gy when using their own calibration curve and triage scoring mode. However, all doses were satisfactory at 4 Gy. Six laboratories had estimated doses within 95% uncertainty limits at 0 Gy, seven at 1.5 Gy, and four at 4 Gy. While the mean dose for sample C was significantly biased using robust algorithms, applying weights to compensate for the laboratory's analysis expertise reduced the bias by half. The bias from delivered doses was only notable for sample C. Using the common calibration curve for dose estimation reduced the standard deviation (s*) estimated by robust methods for all three samples. CONCLUSIONS: The results underscore the significance of performing interlaboratory comparison exercises that involve digitized and electronically transmitted images, even when analyzing non-irradiated samples. In situations where the participating laboratories possess different levels of proficiency, it may prove essential to employ weighted robust algorithms to achieve precise outcomes.

Genetic ancestry and radical prostatectomy findings in Hispanic/Latino patients.

Background: African ancestry is a known factor associated with the presentation and aggressiveness of prostate cancer (PC). Hispanic/Latino populations exhibit varying degrees of genetic admixture across Latin American countries, leading to diverse levels of African ancestry. However, it remains unclear whether genetic ancestry plays a role in the aggressiveness of PC in Hispanic/Latino patients. We explored the associations between genetic ancestry and the clinicopathological data in Hispanic/Latino PC patients from Colombia. Patients and methods: We estimated the European, Indigenous and African genetic ancestry, of 230 Colombian patients with localized/regionally advanced PC through a validated panel for genotypification of 106 Ancestry Informative Markers. We examined the associations of the genetic ancestry components with the Gleason Grade Groups (GG) and the clinicopathological characteristics. Results: No association was observed between the genetic ancestry with the biochemical recurrence or Gleason GG; however, in a two groups comparison, there were statistically significant differences between GG3 and GG4/GG5 for European ancestry, with a higher mean ancestry proportion in GG4/GG5. A lower risk of being diagnosed at an advanced age was observed for patients with high African ancestry than those with low African ancestry patients (OR: 0.96, CI: 0.92-0.99, p=0.03). Conclusion: Our findings revealed an increased risk of presentation of PC at an earlier age in patients with higher African ancestry compared to patients with lower African ancestry in our Hispanic/Latino patients.

Clinical Features and Treatment Outcomes of Carbapenem-Resistant Pseudomonas aeruginosa Keratitis.

Importance: Evaluation of the microbiological diagnostic profile of multidrug-resistant Pseudomonas aeruginosa keratitis and potential management with rose bengal-photodynamic antimicrobial therapy (RB-PDAT) is important. Objective: To document the disease progression of carbapenemase-resistant P aeruginosa keratitis after an artificial tear contamination outbreak. Design, Setting, and Participants: This retrospective observation case series included 9 patients 40 years or older who presented at Bascom Palmer Eye Institute and had positive test results for multidrug-resistant P aeruginosa keratitis between January 1, 2022, and October 31, 2023. Main Outcomes and Measures: Evaluation of type III secretion phenotype, carbapenemase-resistance genes blaGES and blaVIM susceptibility to antibiotics, and in vitro and in vivo outcomes of RB-PDAT against multidrug-resistant P aeruginosa keratitis. Results: Among the 9 patients included in the analysis (5 women and 4 men; mean [SD] age, 73.4 [14.0] years), all samples tested positive for exoU and carbapenemase-resistant blaVIM and blaGES genes. Additionally, isolates were resistant to carbapenems as indicated by minimum inhibitory concentration testing. In vitro efficacy of RB-PDAT indicated its potential application for treating recalcitrant cases. These cases highlight the rapid progression and challenging management of multidrug-resistant P aeruginosa. Two patients were treated with RB-PDAT as an adjuvant to antibiotic therapy and had improved visual outcomes. Conclusions and Relevance: This case series highlights the concerning progression in resistance and virulence of P aeruginosa and emphasizes the need to explore alternative therapies like RB-PDAT that have broad coverage and no known antibiotic resistance. The findings support further investigation into the potential effects of RB-PDAT for other multidrug-resistant microbes.

Undifferentiated Embryonal Sarcoma of the Liver in Pediatrics: A Diagnostic Challenge With Implications for Early Management.

A 10-year-old boy was evaluated for intermittent colicky abdominal pain, general malaise, and asthenia. Imaging revealed a solid liver lesion. Subsequent biopsy and extension studies diagnosed the lesion as undifferentiated embryonal sarcoma of the liver, classified as PRETEXT II, group III according to the postoperative staging system of the Intergroup Study for Soft Tissue Sarcomas. He underwent neoadjuvant chemotherapy using alternating cycles of ifosfamide, doxorubicin, vincristine, D-actinomycin, and cyclophosphamide. This was followed by surgical intervention and two additional adjuvant chemotherapy cycles, resulting in a complete disease response. The patient remains in follow-up and shows no signs of relapse 28 months post-diagnosis. Undifferentiated embryonal sarcoma of the liver is a rare and often misdiagnosed condition that can be mistaken for a benign disease. Its prognosis hinges on timely and accurate diagnosis, which is essential for effectively treating patients with this aggressive pathology with a high mortality risk. Notably, there is no standard treatment approach. In our case, we implemented therapeutic strategies from various literature reports, yielding a promising outcome and positive patient progression.

Determination of TMPRSS2-ERG, SPOP, FOXA1, and IDH1 prostate cancer molecular subtypes in Colombian patients and their possible implications for prognosis.

Prostate cancer (PCa) is one of cancer with of the highest incidence and mortality worldwide. Current disease prognostic markers do not differentiate aggressive from indolent PCa with sufficient certainty, and characterization by molecular subtypes has been sought to allow a better classification. TMPRSS2-ERG, SPOP, FOXA1, and IDH1 molecular subtypes have been described, but the association of these subtypes with prognosis in PCa is unclear; their frequency in Colombian patients is also unknown. Formalin-fixed and paraffin-embedded samples of radical prostatectomy from 112 patients with PCa were used. The TMPRSS2-ERG subtype was assessed with fluorescent in situ hybridization. The mutations in SPOP, FOXA1, and IDH1 in hot-spot regions were evaluated using Sanger sequencing. Fusion was detected in 71 patients (63.4%). No statistically significant differences were found between the state of fusion and the variables analyzed. In the 41 fusion-negative cases (36.6%), two patients (4.9%) had missense mutations in SPOP (p.F102C and p.F133L), representing a 1.8% of the overall cohort. The low frequency of this subtype in Colombians could be explained by the reported variability in the frequency of these mutations according to the population (5%-20%). No mutations were found in FOXA1 in the cases analyzed. The synonym SNP rs11554137 IDH1105GGT was found in tumor tissue but not in the normal tissue in one case. A larger cohort of Colombian PCa patients is needed for future studies to validate these findings and gain a better understanding of the molecular profile of this cancer in our population and if there are any differences by Colombian regions.

Assessment methods for inter-laboratory comparisons of the dicentric assay.

PURPOSE: To test the performance of different algorithms that can be used in inter-laboratory comparisons based on dicentric chromosome analysis, and to evaluate the impact of considering a priori values different to calculate individual laboratory performance based on the ionizing radiation dose estimation. METHODS: Mean and standard deviation estimations in inter-laboratory comparisons are tested on simulated data and data from previously published inter-laboratory comparisons using three robust algorithms, Algorithm A, Algorithm B and Q/Hampel, all programmed in R-project language and implemented in a Shiny application. The simulated data were generated assuming three different probabilities to contaminate inter-laboratory comparisons samples with atypical dose values. Comparison between different algorithms was also done using published exercises where blood samples were irradiated at 0 and 0.7 Gy that represent a challenge for the assessment of an inter-laboratory comparison. RESULTS: The best performance was obtained with the Q/Hampel algorithm for the estimation of the dose mean and with the Algorithm B for the estimation of the dose standard deviation under the conditions tested in the simulations. The Q/Hampel algorithm showed the best performance when non-irradiated samples were evaluated and there was a high proportion of identical values. The presence identical values cause the Algorithm B to fail. Real examples illustrating the need to consider standard deviation priors, and the need to use algorithms resistant to a high proportion of identical values are presented. CONCLUSIONS: Q/Hampel algorithm is a serious candidate to estimate the dose mean in the inter-laboratory comparisons, and to estimate both parameters when the proportion of identical values equals or higher than the half of the results. When the proportion of identical values is less than the half of the results, the Algorithm B should be considered as a candidate to estimate the standard deviation in the inter-laboratory comparisons with small number of laboratories. We remark that special attention is needed to establish prior definitions of standard deviation in the assessment of inter-laboratory dicentric assay comparisons.

Determination of ERG(+), EZH2, NKX3.1, and SPINK-1 subtypes to evaluate their association with clonal origin and disease progression in multifocal prostate cancer.

BACKGROUND: The prognostic relevance of prostate cancer (PCa) molecular subtypes remains controversial, given the presence of multiple foci with the possibility of different subtypes in the same patient. AIM: To determine the clonal origin of heterogeneity in PCa and its association with disease progression, SPOP, ERG(+), EZH2, NKX3.1, and SPINK-1 subtypes were analyzed. METHODS: A total of 103 samples from 20 PCa patients were analyzed; foci of adjacent non-tumor prostate tissue, HGPIN, GL3, GL4, GL5, and LN were examined to determine the presence of the TMPRSS2-ERG fusion and ERG, EZH2, NKX3.1, and SPINK-1 expression levels, using RT-PCR. Mutations in exons 6 and 7 of the SPOP gene were determined by sequencing. The presence of subtypes and molecular patterns were identified by combining all subtypes analyzed. To establish the clonal origin of multifocal PCa, molecular concordance between different foci of the same patient was determined. Association of these subtypes with histopathological groups and time to biochemical recurrence (BCR) was assessed. RESULTS: No mutation was found in SPOP in any sample. The ERG(+) subtype was the most frequent. The molecular pattern containing all four PCa subtypes was only detected in 3 samples (4%), all LN, but it was the most frequent (40%) in patients. Molecular discordance was the predominant status (55%) when all analyzed molecular characteristics were considered. It was possible to find all subtypes, starting as a preneoplastic lesion, and all but one LN molecular subtype were ERG(+) and NKX3.1 subtypes. Only the expression of the NKX3.1 gene was significantly different among the histopathological groups. No association was found between BCR time in patients and molecular subtypes or molecular concordance or between clinicopathological characteristics and molecular subtypes of ERG, EZH2, and SPINK-1. CONCLUSION: The predominance of molecular discordance in prostatic foci per patient, which reflects the multifocal origin of PCa foci, highlights the importance of analyzing multiple samples to establish the prognostic and therapeutic relevance of molecular subtypes in a patient. All the subtypes analyzed here are of early onset, starting from preneoplastic lesions. NKX3.1 gene expression is the only molecular characteristic that shows a progression pattern by sample.

Metabolic pathways enriched according to ERG status are associated with biochemical recurrence in Hispanic/Latino patients with prostate cancer.

BACKGROUND: The role of ERG-status molecular subtyping in prognosis of prostate cancer (PCa) is still under debate. In this study, we identified differentially expressed genes (DEGs) according to ERG-status to explore their enriched pathways and implications in prognosis in Hispanic/Latino PCa patients. METHODS: RNA from 78 Hispanic PCa tissues from radical prostatectomies (RP) were used for RNA-sequencing. ERGhigh /ERGlow tumor groups were determined based on the 1.5-fold change median expression in non-tumor samples. DEGs with a False Discovery Rate (FDR) < 0.01 and a fold change >2 were identified between ERGhigh and ERGlow tumors and submitted to enrichment analysis in MetaCore. Survival and association analyses were performed to evaluate biochemical recurrence (BCR)-free survival. RESULTS: The identification of 150 DEGs between ERGhigh and ERGlow tumors revealed clustering of most of the non-BCR cases (60%) into de ERGhigh group and most of the BCR cases (60.8%) in ERGlow group. Kaplan-Meier survival curves showed a worst BCR-free survival for ERGlow patients, and a significant reduced risk of BCR was observed for ERGhigh cases (OR = 0.29 (95%CI, 0.10-0.8)). Enrichment pathway analysis identified metabolic-related pathways, such as the renin-angiotensin system and angiotensin maturation system, the linoleic acid metabolism, and polyamines metabolism in these ERG groups. CONCLUSIONS: ERGlow tumor cases were associated with poor BCR-free survival in our Hispanic/Latino patients, with metabolism-related pathways altered in the BCR progression. IMPACT: Our findings suggest the need to dissect the role of diet, metabolism, and lifestyle as risk factors for more aggressive PCa subtypes.

Inicio de la Dosimetría Biológica en Costa Rica y su importancia en la atención de poblaciones sobreexpuestas a radiaciones / Beginning of Biological Dosimetry in Costa Rica and its importance in the care of populations overexposed to ionizing radiation

Resumen Introducción: el laboratorio de citogenética del Instituto de Investigaciones en Salud (INISA) de la Universidad de Costa Rica estableció un Servicio de Dosimetría Biológica en enero del 2020 utilizando biomarcadores citogenéticos de exposición a radiaciones ionizantes. Es el primero de su tipo en la región centroamericana. Objetivo: establecer un servicio de dosimetría biológica para Costa Rica, elaborando una curva de calibración dosis-efecto para rayos gamma. Metodología: para la realización de la curva de calibración se irradiaron muestras de sangre periférica in vitro con rayos gamma de dos voluntarios, uno femenino y otro masculino, en 11 puntos de dosis en el rango de 0 a 5 Gy. Se cultivó la sangre acorde a los protocolos internacionales durante 48 horas y se registraron las aberraciones inducidas. Los programas Dose Estimate V5.2 y R versión 4.03 se utilizaron para el cálculo de los coeficientes de la curva de calibración que correlaciona la frecuencia de cromosomas dicéntricos con la dosis. Resultados: los coeficientes de la curva son α: 0.02737±0.00658, ß: 0,05938±0,00450 y C: 0.00129±0.00084. Estos coeficientes tienen valores similares a los reportados internacionalmente. La curva se validó calculando dos dosis incógnitas, en la primera incógnita la dosis suministrada fue de 1,5 Gy y la dosis estimada fue 1,47 Gy y en la segunda la dosis suministrada fue de 4 Gy y la dosis estimada fue 3,616 Gy, para ambos casos no existen diferencias estadísticamente significativas entre las dosis suministradas y las estimadas. Conclusiones: actualmente El Servicio de Dosimetría Biológica del INISA puede estimar dosis absorbida en personas que se sospecha de una sobre exposición a rayos gamma en personal ocupacionalmente expuesto o personas involucradas en un accidente radiológico.

Abstract Introduction. The cytogenetics laboratory of the Health Research Institute (INISA) of the University of Costa Rica established a Biological Dosimetry Service in January 2020 using cytogenetic biomarkers of exposure to ionizing radiation. It is the first of its kind in the Central American region. Objective: establish a biological dosimetry service for Costa Rica, developing a dose-effect calibration curve for gamma rays. Methodology: to carry out the calibration curve, peripheral blood samples from two volunteers, one female and the other male, were irradiated in vitro with gamma rays, at 11 dose points in the range of 0 to 5 Gy. Blood was cultured according to international protocols for 48 hours and induced aberrations were recorded. The Dose Estimate V5.2 and R version 4.03 programs were used to calculate the coefficients of the calibration curve that correlates the frequency of dicentric chromosomes with the dose. Results: the coefficients of the curve are α: 0.02737 ± 0.00658, ß: 0.05938 ± 0.00450 and C: 0.00129 ± 0.00084. These coefficients have values similar to those reported internationally. The curve was validated by calculating two unknown doses, in the first unknown case the delivered dose was 1.5 Gy and the estimated dose was 1.47 Gy and in the second case the delivered dose was 4 Gy and the estimated dose was 3.616 Gy. for both cases there are no statistically significant differences between the delivered and estimated doses. Conclusions: the Biological Dosimetry Service of the INISA can estimate absorbed dose in persons suspected of overexposure to gamma rays in occupationally exposed personnel or persons involved in a radiological accident.Health is loaded with symbolisms and practical manifestations that differ according to social groups and sociocultural contexts. In order to make everyday life and needs visible, the Theoretical Paradigm of Social Representations provides the theoretical-methodological bases necessary to understand the common sense knowledge associated with health among the Nicaraguan migrant population in Costa Rica. Methodology: Qualitative study with ethnographic approach that aimed to identify the social representation of health, through the process of objectification, present among Nicaraguan migrants living in Costa Rica. Data collected through semi-structured interviews, participant observation, and field diaries. Processing according to Content Analysis. Results: The social representation of health found behaves analogously to a formula; where, the search for peaceful environments is added to the achievement of financial stability to result in two interdependent representations: 1) Health as physical-mental strength; and 2) Health as a future and abstract sensation of well-being, happiness and transcendence. The socio-political antecedents in Nicaragua, the migratory process, and the adaptation to Costa Rica play a preponderant role in shaping the representation on health. Conclusion: Social representations about health have direct practical implications on the ways of life and needs of migrant groups. Understanding their common sense knowledge allows to move towards more contextualized public policies. More integration of the thoughts, opinions and feelings of migrants in decision-making platforms is recommended.

Nocardia keratitis: amikacin nonsusceptibility, risk factors, and treatment outcomes.

PURPOSE: To report the increasing trends in Nocardia keratitis species diversity and in vitro antibiotic susceptibility, to demonstrate contact lens wear as a risk factor, and to report visual acuity outcomes after treatment. METHODS: A retrospective clinical case series was performed at a single academic referral center which identified 26 patients with culture-confirmed Nocardia keratitis between 2014 and 2021. A combination of conventional microbiology and molecular techniques were used to identify isolates. Antibiotic susceptibilities were determined using both commercial and in-house laboratory methods. Microbiology and electronic medical records were used to characterize patients' clinical profiles. RESULTS: Patients' median age was 32.5 years with a 2:1 male to female ratio. Eighty-four percent (n = 21/25) of patients were diagnosed within two weeks of symptom onset. Nocardia amikacinitolerans (n = 11/26) was the most recovered Nocardia isolate among study patients. Sixty-four percent (n = 16/25) of all isolates, including all 11 N. amikacinitolerans isolates, were resistant to amikacin. All isolates were susceptible to trimethoprim sulfamethoxazole. Contact lens wear was the leading identified risk factor (n = 23/26) in this population. Median time to resolution was 44 days (n = 23, range: 3-190 days). Seventy-one percent of patients (n = 15/21) had a final visual acuity of 20/40 or better. CONCLUSION: Amikacin resistant Nocardia isolates were the majority in the current study. Trimethoprim sulfamethoxazole may be the preferred alternative antibiotic treatment based on in vitro susceptibilities. Contact lens wear was the major risk factor for Nocardia keratitis in South Florida. Overall visual acuity treatment outcomes of patients were favorable.

Quistes mesoteliales benignos con posible origen en las trompas de Falopio resecados por laparotomía / Benign mesothelial cysts with possible origin in the Fallopian tubes resected by laparotomy

Introducción. Los quistes mesoteliales benignos son una entidad poco frecuente, que ocurren especialmente en mujeres en edad reproductiva. Se deben a una proliferación anómala del mesotelio que puede ser originada en varias estructuras intraabdominales e inicialmente es asintomática. Caso clínico. Se presenta el caso de una mujer de 20 años con un cuadro sugestivo de neoplasia maligna, en quien se confirmó el diagnóstico de quiste mesotelial originado en la trompa de Falopio derecha. Se realizó tratamiento quirúrgico exitoso. Discusión. A pesar de la estrecha relación de esta entidad con el útero y los ovarios, no se encuentran reportes de quistes mesoteliales originados a partir de las trompas de Falopio. El tratamiento de los quistes mesoteliales es quirúrgico y en el caso de esta paciente se hizo con la finalidad de mejorar los síntomas y erradicar la enfermedad. Las decisiones fueron tomadas basadas en la opinión de expertos en oncología en una junta de tumores gastrointestinales. Conclusiones. Los quistes mesoteliales son neoplasias de baja incidencia, pero se deben tener en cuenta como diagnóstico diferencial de los tumores abdominales. Se presenta el caso de una paciente tratada de forma quirúrgica con resultados exitosos y seguimiento a un año sin recurrencias

Introduction. Benign mesothelial cysts (BMC) are a rare entity that occurs especially in women of reproductive age. It is due to an abnormal proliferation of the mesothelium that can originate from various intra-abdominal structures and it is initially asymptomatic. Clinical case. This is a case of a 20-year-old woman with a suspicious malignant neoplasia, in whom the diagnosis of a mesothelial cyst originating in the right Fallopian tube was confirmed. Successful surgical treatment was achieved. Discussion. Despite the close relationship of this entity with the uterus and ovaries, there are no reports of me-sothelial cysts originating from the Fallopian tubes. The treatment of mesothelial cysts is surgical and in the case of this patient it was performed in order to improve the symptoms and eradicate the disease. The decisions were taken based on the oncologists' expert opinion of the gastrointestinal tumor board. Conclusions. Mesothelial cysts are neoplasms of low incidence, but they should be considered as a differential diagnosis of abdominal tumors. The case of a patient treated surgically with successful results and a one-year follow-up without recurrences is presented

Adult Wilms' Tumor: Case Report and Literature Review.

Wilms' tumor is childhood's most common renal tumor, and its presentation in the adult age is extremely rare. Due to the low frequency in adults, no standard management guidelines are available for this population, also the natural history of the disease and management is unclear. We present a case report of a 31-year-old woman with metastatic Wilms' tumor, with lymph node, lung and liver involvement; systemic treatment with chemotherapy was started, with complete clinical response. Finally, a literature review is performed to showcase the differences in the clinical course, prognosis, and treatment alternatives, in adult disease compared to childhood.

Presence of SARS-CoV-2 Viral RNA in Aqueous Humor of Asymptomatic Individuals.

PURPOSE: The purpose of this study was to determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is detectable in the aqueous of asymptomatic individuals presenting for ophthalmic surgery. DESIGN: Prospective cross-sectional study. METHODS: Setting and participants: all patients undergoing anterior segment surgery at an ambulatory surgical center (ASC) belonging to a tertiary academic center in South Florida during a 102-day period between June and September 2020 received nasal swab testing for SARS-CoV-2 and underwent a relevant review of symptoms prior to surgery, with negative results required for both in order to proceed with surgery. Main outcomes and measurements: a small sample of aqueous humor (approximately 0.2 cc) was acquired at the beginning of anterior segment surgery from all participants. Aqueous humor was analyzed for SARS-CoV-2 viral ribonucleic acid (RNA) using real-time reverse transcriptase polymerase chain reaction. Demographic information was acquired from participants for secondary analyses. RESULTS: A total of 70 samples were acquired. Of those, 39 samples were excluded due to insufficient material or inconclusive results. Of 31 samples that were successfully analyzed, 6 (19.4%) demonstrated detectable SARS-CoV-2 RNA. None of the 6 individuals (0%) with detectable viral RNA in aqueous humor reported symptoms during the year, compared to 2 of 25 individuals (8%) with negative samples (P = 1). Positive samples were distributed throughout the study period, including both the first and the last days of enrollment. CONCLUSIONS: The presence of SARS-CoV-2 viral RNA in aqueous despite negative nasal swab testing confirmed its presence beyond the blood-ocular barrier in asymptomatic individuals and raises the possibility that the virus may persist in immunoprivileged spaces despite an absence of symptoms.

La importancia de la determinación del HER2 en el cáncer gástrico avanzado: a propósito de un caso clínico / Importance of HER2 status determination in advanced gastric cancer: A case study

Resumen El cáncer gástrico avanzado es una entidad que incluye dos situaciones clínicas distintas: el cáncer gástrico localmente avanzado no resecable y la enfermedad metastásica, cuyo tratamiento estándar es la quimioterapia. La sobreexpresión del receptor 2 del factor de crecimiento epidérmico humano (HER2) se puede presentar en esta enfermedad de un 9 % a un 38 % y ha sido el primer biomarcador predictivo utilizado para el tratamiento dirigido con trastuzumab en pacientes con tumores gástricos y de la región gastroesofágica avanzados. Se presenta en este artículo el caso de un paciente con cáncer gástrico avanzado con HER2 positivo manejado con quimioterapia convencional más trastuzumab como terapia blanco con adecuada respuesta clínica.

Abstract Advanced gastric cancer (AGC) is an entity that encompasses two distinct clinical situations: locally advanced unresectable gastric cancer and metastatic disease, with chemotherapy as the standard treatment. HER2 overexpression can occur in 9% to 38% of the cases with this disease and has been the first predictive biomarker used for trastuzumab-targeted therapy in patients with advanced gastric and gastroesophageal tumors. This article presents a patient with AGC and positive HER2 treated with conventional chemotherapy plus trastuzumab as targeted therapy with adequate clinical response.

Decoding the heterogeneous landscape in the development prostate cancer.

Prostate cancer (PCa) is characterized as being histologically and molecularly heterogeneous; however, this is not only incorrect among individuals, but also at the multiple foci level, which originates in the prostate gland itself. The reasons for such heterogeneity have not been fully elucidated; however, understanding these may be crucial in determining the course of the disease. PCa is characterized by a complex network of chromosomal rearrangements, which simultaneously deregulate multiple genes; this could explain the appearance of exclusive events associated with molecular subtypes, which have been extensively investigated to establish clinical management and the development of therapies targeted to this type of cancer. From a clinical aspect, the prognosis of the patient has focused on the characteristics of the index lesion (the largest focus in PCa); however, a significant percentage of patients (11%) also exhibit an aggressive secondary foci, which may determine the prognosis of the disease, and could be the determining factor of why, in different studies, the classification of the subtypes does not have an association with prognosis. Due to the aforementioned reasons, the analysis of molecular subtypes in several foci, from the same individual could assist in determining the association between clinical evolution and management of patients with PCa. Castration-resistant PCa (CRPC) has the worst prognosis and develops following androgen ablation therapy. Currently, there are two models to explain the development of CRPC: i) The selection model and ii) the adaptation model; both of which, have been found to include alterations described in the molecular subtypes, such as Enhancer of zeste 2 polycomb repressive complex 2 subunit overexpression, isocitrate dehydrogenase (NAPD+)1 and forkhead box A1 mutations, suggesting that the presence of specific molecular alterations could predict the development of CRPC. This type of analysis could lead to a biological understanding of PCa, to develop personalized medicine strategies, which could improve the response to treatment thus, avoiding the development of resistance. Therefore, the present review discusses the primary molecular factors, to which variable heterogeneity in PCa progress has been attributed.

CPHR: 35 años al Servicio de la Protección Radiológica, la Salud y el Medio Ambiente / CPHR: 35 years at the Service of Radiological Protection, Health and the Environment

Resumen El Centro de Protección e Higiene de las Radiaciones fue fundado en 1985 para sustentar la aplicación segura de las tecnologías nucleares en Cuba. En la actualidad la institución es considerada como una referencia nacional y regional en materia de seguridad radiológica, gracias a una sólida estrategia institucional que aporta de manera sostenida soluciones a problemas prioritarios del país. Este trabajo presenta una reseña de los principales resultados del centro hasta la fecha.

Abstract The Center for Radiation Protection and Hygiene was founded in 1985 to support the safe application of nuclear technologies in Cuba. Nowdays, the institution is considered as a national and regional reference for radiation protection , thanks to the comprehensive institutional strategy that support the solutions of the problems with priority in the country. The paper presents the overview about the main results of the center up today.

El proceso de iniciación deportiva escolar en voleibol: una mirada de renovación para su aprendizaje / O processo de iniciação desportiva escolar no voleibol: um olhar de renovação para a sua aprendizagem / The process of initial sport formation in volleyball: a glance of renovation for its learning

Resumen El proceso de iniciación deportiva escolar en el voleibol constituye un tema de actualidad en el ámbito de la investigación científico-educativa, que analizado en relación con el contexto y la época en que se desenvuelve, necesita enriquecer sus contenidos desde nuevas perspectivas pedagógicas. El objetivo de este trabajo persigue caracterizar el proceso de iniciación deportiva escolar del Voleibol en la Eide "Ormani Arenado LLonch", de Pinar del Río. Para lograr este fin, se utilizaron métodos del nivel teórico (histórico lógico, inductivo-deductivo, modelación, analítico-sintético) y del nivel empírico (revisión documental, observación, encuestas, entrevistas), para delimitar las esencias del objeto y organizar científicamente la obtención de los resultados investigativos. Dentro de los resultados, figura la sistematización realizada que posibilitó determinar tendencias en el desarrollo del objeto, definirlo y establecer tres dimensiones para su estudio (cognitiva-procedimental, gestión del trabajo metodológico y axiológica) con sus respectivas definiciones, precisar fortalezas y debilidades que lo caracterizan en la institución deportiva de referencia, así como la integración de resultados del diagnóstico en el establecimiento de sus regularidades. Se afirma que las dimensiones de la variable analizada, en su estado actual, presentan aspectos afectados, entendidos como retos que merecen ser tratados por el Departamento metodológico de Alto Rendimiento.

Resumo O processo de iniciação desportiva escolar no voleibol é uma questão actual no campo da investigação científico-educativa, que analisada em relação ao contexto e ao tempo em que se realiza, necessita de enriquecer os seus conteúdos a partir de novas perspectivas pedagógicas. O objectivo deste trabalho é caracterizar o processo de iniciação desportiva escolar do Voleibol na EIDE "Ormani Arenado LLonch" em Pinar del Río. Para atingir este objectivo, foram utilizados métodos de nível teórico (histórico-lógico, indutivo-dedutivo, modelação, analítico-sintético) e de nível empírico (revisão documental, observação, inquéritos, entrevistas) para delimitar as essências do objecto e para organizar cientificamente a obtenção dos resultados da investigação. Dentre os resultados, destaca-se a sistematização realizada que permitiu determinar tendências no desenvolvimento do objeto, defini-lo e estabelecer três dimensões para seu estudo (cognitivo-processal, gestão do trabalho metodológico e axiológico) com suas respectivas definições, especificar os pontos fortes e fracos que o caracterizam na instituição desportiva de referência, bem como a integração dos resultados do diagnóstico no estabelecimento de suas regularidades. Afirma-se que as dimensões da variável analisada, no seu estado atual apresentam aspectos afetados, entendidos como desafios que merecem ser tratados pelo Departamento de Metodologia de Alta Performance.

Abstract The process of school sports initiation in volleyball is a current issue in the field of scientific-educational research, which analyzed in relation to the context and the time in which it takes place, needs to enrich its contents from new pedagogical perspectives. The objective of this work is to characterize the process of school sports initiation of Volleyball in the "Ormani Arenado LLonch" EIDE in Pinar del Río. To achieve this goal, methods of the theoretical level (historical-logical, inductive-deductive, modeling, analytical-synthetic) and of the empirical level (documentary review, observation, surveys, interviews) were used to delimit the essences of the object and to scientifically organize the obtaining of the research results. Among the results, there is the systematization carried out that allowed to determine tendencies in the development of the object, to define it and to establish three dimensions for its study (cognitive-procedural, management of the methodological work and axiological) with its respective definitions, to specify strengths and weaknesses that characterize it in the sport institution of reference, as well as the integration of results of the diagnosis in the establishment of its regularities. It is stated that the dimensions of the analyzed variable, in its current state, present affected aspects, understood as challenges that deserve to be treated by the High Performance Methodological Department.

In vitro Susceptibilities of Methicillin-Susceptible and Resistant Staphylococci to Traditional Antibiotics Compared to a Novel Fluoroquinolone.

BACKGROUND: To assess the in-vitro efficacy of delafloxacin, a new fourth generation fluoroquinolone, against Staphylococcus vitreous isolates from patients with clinically diagnosed endophthalmitis. This is the first investigation of delafloxacin in ocular tissues. METHODS: Intravitreal isolates of culture-proven S. aureus and S. epidermidis were identified between 2014 and 2018. Minimum inhibitor concentrations (MIC) were determined using ETEST strips. The antibiotic susceptibilities were tested against a panel of drugs including glycopeptides such as vancomycin, as well as traditional and newer fluoroquinolones (levofloxacin, moxifloxacin, and delafloxacin). RESULTS: Of 45 total isolates identified between 2014 and 2018, 13% (6) were methicillin-resistant S. aureus (MRSA), 9% (4) were methicillin-sensitive S. aureus (MSSA), 53% (24) were methicillin-resistant S. epidermidis (MRSE), and 24% (11) were methicillin-sensitive S. epidermidis (MSSE). Among the fluoroquinolones, resistance rates were 61% for levofloxacin, 50% for moxifloxacin, and 12% for delafloxacin. Inter-class comparisons between delafloxacin and the two other fluoroquinolones demonstrated higher Gram-positive susceptibility to delafloxacin (p < 0.01). MIC90 values were lowest for delafloxacin (1.0 µg/mL) compared to levofloxacin (8.0 µg/mL) and moxifloxacin (8.0 µg/mL). Vancomycin was 100% effective against all isolates with MIC90 value of 0.75 µg/mL. CONCLUSION: Compared to levofloxacin and moxifloxacin, the newer fluoroquinolone delafloxacin demonstrated the lowest MICs values and lowest rates of resistance for Gram-positive in-vitro S. epidermidis and S. aureus vitreous isolates.

Rose bengal photodynamic antimicrobial therapy to inhibit Pseudomonas aeruginosa keratitis isolates.

To evaluate the in vitro efficacy of rose bengal and riboflavin photodynamic antimicrobial therapy for inhibition the growth of four Pseudomonas aeruginosa (P. aeruginosa) isolates. Four different clinical P. aeruginosa isolates were collected from patients with confirmed keratitis. Each strain was mixed with either sterile water, 0.1% riboflavin solution, or 0.1% rose bengal solution to yield a final bacteria concentration of 1.5 × 107 CFU/mL. Aliquots from each suspension were plated onto nutrient agar in triplicate. Plates were separated into two groups: (1) no irradiation and (2) 5.4 J/cm2 of radiant exposure with custom-made LED irradiation sources. Separate irradiation sources were used for each photosensitizer. The riboflavin groups used a UV-A light source (375 nm) and rose bengal groups used a green light source (525 nm). Plates were photographed at 72 h and custom software measured bacterial growth inhibition. Growth inhibition to riboflavin and rose bengal PDAT showed strain-dependent variability. All four strains of P. aeruginosa showed greatest growth inhibition (89-99%) in the green irradiated-rose bengal group. The UV-A-irradiated riboflavin showed inhibition of 24-44%. UV-A irradiation only showed minimal inhibition (7-14%). There was little inhibitory effect in the non-irradiated photosensitizer groups. Rose bengal PDAT had the greatest inhibitory effect on all four P. aeruginosa isolates. In the UV-A-irradiated riboflavin group, there was moderate inhibition within the irradiation zone; however, there was no inhibition in the non-irradiated groups. These results suggest that rose bengal PDAT may be an effective alternative treatment for Pseudomonas aeruginosa infections.

Gastrectomía laparoscópica casi total con preservación de la rama ascendente de la arteria gástrica izquierda y un 5 % de remanente gástrico. ¿Existe relación con las complicaciones de la anastomosis? / Almost total laparoscopic gastrectomy with preservation of the ascending branch of the left gastric artery and 5 % gastric remnant. Is there a relationship with the complications of the anastomosis

Introducción. Al realizar una gastrectomía distal, el remanente gástrico es irrigado por los vasos gástricos cortos. En este estudio presentamos una serie de casos de gastrectomía distal laparoscópica, con la variante de preservar la rama superior de la arteria gástrica izquierda, con un remanente gástrico pequeño. Métodos. Estudio observacional con intensión analítica, seguimiento de una cohorte retrospectiva de pacientes con cáncer gástrico sometidos a gastrectomía distal radical laparoscópica entre enero 2017 y junio 2019. Se incluyeron todos los pacientes con cáncer gástrico a quienes se les realizó gastrectomía distal radical por laparoscopia. Se estudiaron variables clínicas de los pacientes, variables intraoperatorias, información relacionada con el informe de patología y las complicaciones de la anastomosis gastro-yeyunal. Resultados. Se revisó un total de 61 historias clínicas de pacientes sometidos a gastrectomía distal por laparoscopia, entre quienes se encontró la preservación de la rama ascendente de la arteria gástrica izquierda en el 73,8 % de los pacientes (n=45). El promedio de ganglios resecados fue de 24. Se presentaron un total de 10 complicaciones, ocho relacionadas con la anastomosis (tres estenosis, cuatro filtraciones y un paciente con hemorragia del tracto digestivo superior), y dos con colecciones intrabdominales. En el análisis estadístico no se encontró relación entre la preservación de la rama ascendente de la arteria gástrica izquierda con la presencia de complicaciones. Discusión. La variación que presentamos de la técnica de la gastrectomía distal por laparoscopia cumple con los requisitos oncológicos en los pacientes con cáncer gástrico y no se relaciona con complicaciones de la anastomosis gastro-yeyunal

Introduction. When performing a distal gastrectomy, the gastric remnant is supplied by the short gastric vessels. In this study we present a series of cases of laparoscopic distal gastrectomy, with the variant of preserving the superior branch of the left gastric artery, with a small gastric remnant.Methods. Observational study, follow-up of a retrospective cohort of patients with gastric cancer who underwent laparoscopic radical distal gastrectomy between January 2017 and June 2019. All patients with gastric cancer who underwent laparoscopic radical distal gastrectomy were included. Clinical variables of the patients, intraopera-tive variables, information related to the pathology report and complications of the gastro-jejunal anastomosis were studied.Results. A total of 61 medical records of patients undergoing laparoscopic distal gastrectomy were reviewed; pres-ervation of the ascending branch of the left gastric artery was found in 73.8% of the patients (n = 45). The average number of lymph nodes resected was 24. There were a total of 10 complications, eight related to the anastomosis (three strictures, four leaks and one patient with bleeding from the upper digestive tract), and two patients who presented intra-abdominal collections. No statistical relationship was found between the preservation of the ascending branch of the left gastric artery and the presence of complications.Discusion. The variation that we present of the laparoscopic distal gastrectomy technique meets the oncological requirements in patients with gastric cancer and is not related to complications of the gastrojejunal anastomosis.