Deep learning-based scoring of tumour-infiltrating lymphocytes is prognostic in primary melanoma and predictive to PD-1 checkpoint inhibition in melanoma metastases.

BACKGROUND: Recent advances in digital pathology have enabled accurate and standardised enumeration of tumour-infiltrating lymphocytes (TILs). Here, we aim to evaluate TILs as a percentage electronic TIL score (eTILs) and investigate its prognostic and predictive relevance in cutaneous melanoma. METHODS: We included stage I to IV cutaneous melanoma patients and used hematoxylin-eosin-stained slides for TIL analysis. We assessed eTILs as a continuous and categorical variable using the published cut-off of 16.6% and applied Cox regression models to evaluate associations of eTILs with relapse-free, distant metastasis-free, and overall survival. We compared eTILs of the primaries with matched metastasis. Moreover, we assessed the predictive relevance of eTILs in therapy-naïve metastases according to the first-line therapy. FINDINGS: We analysed 321 primary cutaneous melanomas and 191 metastatic samples. In simple Cox regression, tumour thickness (p < 0.0001), presence of ulceration (p = 0.0001) and eTILs ≤16.6% (p = 0.0012) were found to be significant unfavourable prognostic factors for RFS. In multiple Cox regression, eTILs ≤16.6% (p = 0.0161) remained significant and downgraded the current staging. Lower eTILs in the primary tissue was associated with unfavourable relapse-free (p = 0.0014) and distant metastasis-free survival (p = 0.0056). In multiple Cox regression adjusted for tumour thickness and ulceration, eTILs as continuous remained significant (p = 0.019). When comparing TILs in primary tissue and corresponding metastasis of the same patient, eTILs in metastases was lower than in primary melanomas (p < 0.0001). In therapy-naïve metastases, an eTILs >12.2% was associated with longer progression-free survival (p = 0.037) and melanoma-specific survival (p = 0.0038) in patients treated with anti-PD-1-based immunotherapy. In multiple Cox regression, lactate dehydrogenase (p < 0.0001) and eTILs ≤12.2% (p = 0.0130) were significantly associated with unfavourable melanoma-specific survival. INTERPRETATION: Assessment of TILs is prognostic in primary melanoma samples, and the eTILs complements staging. In therapy-naïve metastases, eTILs ≤12.2% is predictive of unfavourable survival outcomes in patients receiving anti-PD-1-based therapy. FUNDING: See a detailed list of funding bodies in the Acknowledgements section at the end of the manuscript.

mlf-core: a framework for deterministic machine learning.

MOTIVATION: Machine learning has shown extensive growth in recent years and is now routinely applied to sensitive areas. To allow appropriate verification of predictive models before deployment, models must be deterministic. Solely fixing all random seeds is not sufficient for deterministic machine learning, as major machine learning libraries default to the usage of nondeterministic algorithms based on atomic operations. RESULTS: Various machine learning libraries released deterministic counterparts to the nondeterministic algorithms. We evaluated the effect of these algorithms on determinism and runtime. Based on these results, we formulated a set of requirements for deterministic machine learning and developed a new software solution, the mlf-core ecosystem, which aids machine learning projects to meet and keep these requirements. We applied mlf-core to develop deterministic models in various biomedical fields including a single-cell autoencoder with TensorFlow, a PyTorch-based U-Net model for liver-tumor segmentation in computed tomography scans, and a liver cancer classifier based on gene expression profiles with XGBoost. AVAILABILITY AND IMPLEMENTATION: The complete data together with the implementations of the mlf-core ecosystem and use case models are available at https://github.com/mlf-core.

Clinicopathological Features and Mortality in Patients With Kaposi Sarcoma and HIV: A Retrospective Analysis of a Thirty-Year Study From a Peruvian Oncologic Center.

PURPOSE: Kaposi's sarcoma (KS) is a multifocal angioproliferative disease. In Peru, the implementation of the highly active antiretroviral treatment (HAART) program was in 2005, the model for treating patients with HIV-positive KS shifted to a potential cure. In this study, we aim to compare clinicopathological characteristics and prognostic factors associated with outcomes in patients with HIV-positive KS. METHODS: We developed a retrospective cohort study that includes patients with HIV/AIDS and KS seen in the Instituto Nacional de Enfermedades Neoplasicas between 1987 and 2017. Patients were divided into two groups according to the implementation of HAART in our country: the non-HAART group and those treated with HAART after 2005. Multivariate analysis for overall survival (OS) was performed with the Cox proportional hazard regression model. RESULTS: There was a greater visceral compromise and more extensive oral cavity involvement in the non-HAART group (60% 31.7%, P < .01). Regarding the immune status, there was a significant difference from the CD4 count at 1-year follow-up (73 v 335, P = .01). The CD4/CD8 rate were significant different before QT (0.23 v 0.13, P = .01) and at 1-year follow-up (0.12 v 0.32, P = .03.). The estimated 5-year OS rate was significantly lower (P = .0001) for the non-HAART group (41.7%; 95% CI, 25.9 to 56.9) compared with the HAART group (79.3%; 95% CI, 66.8 to 87.5). In the multivariate model for OS, full-HAART regimen and previous diagnosis of HIV/AIDS (P < .01) were significantly associated with longer survival. CONCLUSION: Clinical and demographic characteristics of our patients are compatible with the literature, but we report a higher rate of gastrointestinal involvement. Furthermore, our findings provide evidence for the importance of HAART and its ability to reduce KS-related mortality.

A data management infrastructure for the integration of imaging and omics data in life sciences.

BACKGROUND: As technical developments in omics and biomedical imaging increase the throughput of data generation in life sciences, the need for information systems capable of managing heterogeneous digital assets is increasing. In particular, systems supporting the findability, accessibility, interoperability, and reusability (FAIR) principles of scientific data management. RESULTS: We propose a Service Oriented Architecture approach for integrated management and analysis of multi-omics and biomedical imaging data. Our architecture introduces an image management system into a FAIR-supporting, web-based platform for omics data management. Interoperable metadata models and middleware components implement the required data management operations. The resulting architecture allows for FAIR management of omics and imaging data, facilitating metadata queries from software applications. The applicability of the proposed architecture is demonstrated using two technical proofs of concept and a use case, aimed at molecular plant biology and clinical liver cancer research, which integrate various imaging and omics modalities. CONCLUSIONS: We describe a data management architecture for integrated, FAIR-supporting management of omics and biomedical imaging data, and exemplify its applicability for basic biology research and clinical studies. We anticipate that FAIR data management systems for multi-modal data repositories will play a pivotal role in data-driven research, including studies which leverage advanced machine learning methods, as the joint analysis of omics and imaging data, in conjunction with phenotypic metadata, becomes not only desirable but necessary to derive novel insights into biological processes.

Listeria bacteremia in patients from a peruvian oncologic institute, 2005-2015. / Bacteriemia por listeria en pacientes de un instituto oncológico peruano, 2005-2015.

Listeriosis infection is a severe disease, with high morbidity and mortality in the immunocompromised patient, especially with disseminated and fatal presentations in cancer patients. A descriptive study was developed to describe the clinical and epidemiologic characteristics in oncologic patients with listeriosis in the Instituto Nacional de Enfermedades Neoplásicas between the years 2005-2015. A total of 29 patients were included; 23 (79.3%) of the listeriosis cases showed up in patients with hematological neoplasia, of which 52.1% was acute lymphatic leukemia and 39.1% non-Hodgkin's lymphoma. The 72.4% of the isolated species correspond to Listeria monocytogenes. Twenty-seven (93.1%) patients met sepsis criteria and twenty-four (82.7%) had neurologic affection. Bacteremia was the most common presentation, followed by meningoencephalitis (20.6%). Global mortality was 75.8%. In conclusion in cancer patients, listeriosis implies high morbidity and mortality. Therefore, the suspicion of this entity is mandatory in onco-hematologic patients with sepsis and acute neurologic symptoms.

La listeriosis es una infección severa de elevada morbimortalidad en el paciente inmunocomprometido, existen formas diseminadas y fatales en el paciente oncológico. Se realizó un estudio descriptivo de las características clínico-epidemiológicas de los pacientes oncológicos con listeriosis atendidos en el Instituto Nacional de Enfermedades Neoplásicas entre 2005 y 2015. Se incluyeron 29 pacientes, 23 (79,3%) casos de listeriosis se presentaron en pacientes con neoplasia hematológica, de los cuales el 52,3% fueron leucemia linfática aguda y 39,1% linfoma no Hodgkin. Listeria monocytogenes representó el 72,4% de las especies aisladas. Veintisiete (93,1%) tuvieron criterios de sepsis y veinticuatro (82,7%) compromiso neurológico al ingreso. La presentación más común fue la bacteriemia, seguida de la meningoencefalitis (20,6%). La mortalidad global fue del 75,8%. Se concluye que la listeriosis conlleva elevada morbimortalidad en el paciente oncohematológico, por lo que debe sospecharse en el paciente admitido con sepsis y/o compromiso neurológico agudo.

International multicentre observational study to evaluate the association between perioperative red blood cell transfusions and 1-year mortality after major cancer surgery (ARCA-1): study design, statistical analysis plan and study protocol.

INTRODUCTION: Blood transfusion is still common in patients undergoing major cancer surgery. Blood transfusion can be associated with poor prognosis in patients with cancer. Perioperative Care in the Cancer Patient -1 (ARCA-1) aims to assess in a large cohort of patients the current incidence, pattern of practice and associations between perioperative blood transfusions and 1-year survival in patients undergoing major cancer surgery. METHODS AND ANALYSIS: ARCA-1 is a prospective international multicentre observational study that will include adult patients scheduled to have major cancer surgical procedures with the intention to cure, and an overnight planned hospital admission. The study will be opened for 1 year for enrolment (7 January 2020-7 February 2021). Each centre will enrol patients for 30 days. The primary endpoint of this study is all-cause mortality 1 year after major cancer surgery. Secondary endpoints are rate of perioperative blood product use, cancer-specific mortality at 1 year and PFSs and 30-day morbidity and mortality. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board at The University of Texas-MD Anderson Cancer Center. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT04491409.

Bacteriemia por listeria en pacientes de un instituto oncológico peruano, 2005-2015 / Listeria bacteremia in patients from a peruvian oncologic institute, 2005-2015

RESUMEN La listeriosis es una infección severa de elevada morbimortalidad en el paciente inmunocomprometido, existen formas diseminadas y fatales en el paciente oncológico. Se realizó un estudio descriptivo de las características clínico-epidemiológicas de los pacientes oncológicos con listeriosis atendidos en el Instituto Nacional de Enfermedades Neoplásicas entre 2005 y 2015. Se incluyeron 29 pacientes, 23 (79,3%) casos de listeriosis se presentaron en pacientes con neoplasia hematológica, de los cuales el 52,3% fueron leucemia linfática aguda y 39,1% linfoma no Hodgkin. Listeria monocytogenes representó el 72,4% de las especies aisladas. Veintisiete (93,1%) tuvieron criterios de sepsis y veinticuatro (82,7%) compromiso neurológico al ingreso. La presentación más común fue la bacteriemia, seguida de la meningoencefalitis (20,6%). La mortalidad global fue del 75,8%. Se concluye que la listeriosis conlleva elevada morbimortalidad en el paciente oncohematológico, por lo que debe sospecharse en el paciente admitido con sepsis y/o compromiso neurológico agudo.

ABSTRACT Listeriosis infection is a severe disease, with high morbidity and mortality in the immunocompromised patient, especially with disseminated and fatal presentations in cancer patients. A descriptive study was developed to describe the clinical and epidemiologic characteristics in oncologic patients with listeriosis in the Instituto Nacional de Enfermedades Neoplásicas between the years 2005-2015. A total of 29 patients were included; 23 (79.3%) of the listeriosis cases showed up in patients with hematological neoplasia, of which 52.1% was acute lymphatic leukemia and 39.1% non-Hodgkin's lymphoma. The 72.4% of the isolated species correspond to Listeria monocytogenes. Twenty-seven (93.1%) patients met sepsis criteria and twenty-four (82.7%) had neurologic affection. Bacteremia was the most common presentation, followed by meningoencephalitis (20.6%). Global mortality was 75.8%. In conclusion in cancer patients, listeriosis implies high morbidity and mortality. Therefore, the suspicion of this entity is mandatory in onco-hematologic patients with sepsis and acute neurologic symptoms.

Bacteriemia por listeria en pacientes de un instituto oncológico peruano, 2005-2015 / Listeria bacteremia in patients from a peruvian oncologic institute, 2005-2015

RESUMEN La listeriosis es una infección severa de elevada morbimortalidad en el paciente inmunocomprometido, existen formas diseminadas y fatales en el paciente oncológico. Se realizó un estudio descriptivo de las características clínico-epidemiológicas de los pacientes oncológicos con listeriosis atendidos en el Instituto Nacional de Enfermedades Neoplásicas entre 2005 y 2015. Se incluyeron 29 pacientes, 23 (79,3%) casos de listeriosis se presentaron en pacientes con neoplasia hematológica, de los cuales el 52,3% fueron leucemia linfática aguda y 39,1% linfoma no Hodgkin. Listeria monocytogenes representó el 72,4% de las especies aisladas. Veintisiete (93,1%) tuvieron criterios de sepsis y veinticuatro (82,7%) compromiso neurológico al ingreso. La presentación más común fue la bacteriemia, seguida de la meningoencefalitis (20,6%). La mortalidad global fue del 75,8%. Se concluye que la listeriosis conlleva elevada morbimortalidad en el paciente oncohematológico, por lo que debe sospecharse en el paciente admitido con sepsis y/o compromiso neurológico agudo.

ABSTRACT Listeriosis infection is a severe disease, with high morbidity and mortality in the immunocompromised patient, especially with disseminated and fatal presentations in cancer patients. A descriptive study was developed to describe the clinical and epidemiologic characteristics in oncologic patients with listeriosis in the Instituto Nacional de Enfermedades Neoplásicas between the years 2005-2015. A total of 29 patients were included; 23 (79.3%) of the listeriosis cases showed up in patients with hematological neoplasia, of which 52.1% was acute lymphatic leukemia and 39.1% non-Hodgkin's lymphoma. The 72.4% of the isolated species correspond to Listeria monocytogenes. Twenty-seven (93.1%) patients met sepsis criteria and twenty-four (82.7%) had neurologic affection. Bacteremia was the most common presentation, followed by meningoencephalitis (20.6%). Global mortality was 75.8%. In conclusion in cancer patients, listeriosis implies high morbidity and mortality. Therefore, the suspicion of this entity is mandatory in onco-hematologic patients with sepsis and acute neurologic symptoms.

Prognostic factors in HIV-positive patients with non-Hodgkin lymphoma: a Peruvian experience.

BACKGROUND: Non-Hodgkin lymphoma (NHL) is the most common cancer in people with HIV. Although 95% of HIV patients are in developing countries like Peru, the majority of these studies have been conducted in developed countries. In this study we aim to evaluate prognostic factors associated with outcomes in HIV positive patients undergoing systemic therapy for treatment of NHL. METHODS: This retrospective study includes patients with NHL seen in the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 2004 to 2014. Patients were divided into two groups: antiretroviral therapy (ART) -naïve (n = 34) and those previously treated, ART-exposed (n = 13), at the time of diagnosis. All patients received chemotherapy and ART. The medical records were reviewed. Data were analyzed using t-test and chi-square test. Survival curves were estimated by the Kaplan-Meier method and comparison was done by log-rank test. Multivariate analysis for overall survival (OS) was performed with the Cox proportional hazard regression model. RESULTS: All ART-exposed patients were from the capital city (p = 0.039); they had significantly lower hemoglobin levels compared to ART-naïve patients (p = 0.026). The median OS was 47.7 months with a 5-yr OS of 36.1%. The median OS for ART naïve patients was significantly higher than that for ART-exposed patients (57.05 and 21.09 months, respectively; p = 0.018). Advanced stage and low serum albumin were associated with lower OS in both groups. Age > 60 was associated with worse outcomes in the ART-naïve cohort. CONCLUSIONS: Advanced stage, low serum albumin and previous ART treatment were the primary prognostic factors associated with poorer outcomes in patients with NHL and HIV infection. In ART-naïve patients, age > 60 was associated with worse outcomes but in this cohort, older patients still had better overall outcomes than ART-exposed patients.

[Tuberculosis That Mimics Cancer: Cases Referred to the National Institute of Neoplastic Diseases, Lima-Peru]. / Tuberculosis que imita cáncer: casos derivados al Instituto Nacional de Enfermedades Neoplásicas, Lima-Perú.

Tuberculosis (TB) is a major public health problem that, due to the clinical variability of its presentation, can be confused with cancer. The aim of this study was to identify the clinical-radiological characteristics and to describe the methodology that allowed to achieve a TB diagnosis in patients referred to the National Institute of Neoplastic Diseases (INEN) with a presumed diagnosis of cancer between 2014 and 2016. The study included 170 patients (52.4% men) with an average age of 41.1 years; 18% presented a history of contact with TB, and 5.9% had had the disease previously. The TB was pulmonary in 22.4% and extrapulmonary in 77.7% of patients. The most frequent symptoms were respiratory, tumor, weight loss, and neurological. The cancer diagnoses most frequently discarded were lymphoma, lung cancer, and brain cancer. The lesions that suggested a neoplasm indicated an advanced clinical stage in 63.5%. Therefore, it follows that the symptoms and images associated with TB can be confused with malignant neoplasms.

La tuberculosis (TB) es un importante problema de salud pública que debido a la variabilidad clínica de su presentación, puede confundirse con una malignidad. El objetivo del estudio fue identificar las características clínico radiológicas y describir la metodología que permitió llegar al diagnóstico de TB en pacientes derivados con presunción diagnóstica de cáncer al Instituto Nacional de Enfermedades Neoplásicas (INEN) entre 2014 y 2016. Se incluyeron 170 pacientes (52,4 % hombres) con edad promedio de 41,1 años, 18 % presentaron antecedentes de contacto con TB y un 5,9 % tuvo previamente la enfermedad. La TB fue pulmonar en 22,4 % y extrapulmonar en 77,7 % de los pacientes. Los síntomas más frecuentes fueron respiratorios, tumoración, pérdida de peso y neurológicos. Los diagnósticos oncológicos descartados con mayor frecuencia fueron linfoma, cáncer pulmonar y cerebral. Las lesiones que sugerían una neoplasia indicaron un estadio clínico avanzado en el 63,5 %. Se concluye que los síntomas e imágenes asociados a TB pueden confundirse con neoplasias malignas.

Tuberculosis que imita cáncer: casos derivados al Instituto Nacional de Enfermedades Neoplásicas, Lima-Perú / Tuberculosis That Mimics Cancer: Cases Referred to the National Institute of Neoplastic Diseases, Lima-Peru

RESUMEN La tuberculosis (TB) es un importante problema de salud pública que debido a la variabilidad clínica de su presentación, puede confundirse con una malignidad. El objetivo del estudio fue identificar las características clínico radiológicas y describir la metodología que permitió llegar al diagnóstico de TB en pacientes derivados con presunción diagnóstica de cáncer al Instituto Nacional de Enfermedades Neoplásicas (INEN) entre 2014 y 2016. Se incluyeron 170 pacientes (52,4 % hombres) con edad promedio de 41,1 años, 18 % presentaron antecedentes de contacto con TB y un 5,9 % tuvo previamente la enfermedad. La TB fue pulmonar en 22,4 % y extrapulmonar en 77,7 % de los pacientes. Los síntomas más frecuentes fueron respiratorios, tumoración, pérdida de peso y neurológicos. Los diagnósticos oncológicos descartados con mayor frecuencia fueron linfoma, cáncer pulmonar y cerebral. Las lesiones que sugerían una neoplasia indicaron un estadio clínico avanzado en el 63,5 %. Se concluye que los síntomas e imágenes asociados a TB pueden confundirse con neoplasias malignas.

ABSTRACT Tuberculosis (TB) is a major public health problem that, due to the clinical variability of its presentation, can be confused with cancer. The aim of this study was to identify the clinical-radiological characteristics and to describe the methodology that allowed to achieve a TB diagnosis in patients referred to the National Institute of Neoplastic Diseases (INEN) with a presumed diagnosis of cancer between 2014 and 2016. The study included 170 patients (52.4% men) with an average age of 41.1 years; 18% presented a history of contact with TB, and 5.9% had had the disease previously. The TB was pulmonary in 22.4% and extrapulmonary in 77.7% of patients. The most frequent symptoms were respiratory, tumor, weight loss, and neurological. The cancer diagnoses most frequently discarded were lymphoma, lung cancer, and brain cancer. The lesions that suggested a neoplasm indicated an advanced clinical stage in 63.5%. Therefore, it follows that the symptoms and images associated with TB can be confused with malignant neoplasms.

Practical Recommendations for Preoperative Skin Antisepsis / Recomendaciones prácticas para la antisepsia preoperatoria de la piel

Abstract The search for strategies for the reduction of Surgical Site infection (SSI) is a priority, given the impact those infections have on the outcome of the patients. The preope rative patient skin antisepsis, has recently gained greater significance in the prevention of SSI, as one of the critical factors, which can be intervened and can reduce the risk of infection. In recent years, comprehensive investigations have been published, not only dedicated to the comparison of antiseptic solutions, application techniques, but also about the importance of preoperative washing, use of surgical tapes and dressings impregnated with antiseptics, and preoperative shaving. This review outlines the key findings related to the preoperative patient's skin antisepsis and offers a protocol with practical recommendations to be implemented in the institutions of our country. It provides evidence based recommendations about the use of antiseptic solutions (povidone iodine, chlorhexidine, chlorhexidine plus alcohol, etc.) with emphasis on the advantages and disadvantages of each one.

The Effect of Genistein Supplementation on Vitamin D Levels and Bone Turnover Markers during the Summer in Healthy Postmenopausal Women: Role of Genotypes of Isoflavone Metabolism.

AIMS: The objective of this study was to determine whether vitamin D and genistein supplementation had an additive beneficial effect on levels of vitamin D and bone markers and whether this effect was mediated by genes regulating isoflavone metabolism. MATERIALS AND METHODS: We carried out a prospective study in postmenopausal women randomized to calcium and vitamin D supplementation or calcium, vitamin D, and genistein supplementation. Vitamin D, parathyroid hormone (PTH), cross-linked C-telopeptide (CTX), and procollagen 1 N-terminal (P1NP) were determined by electrochemiluminescence. Three SNPs - rs2231142 (ABCG2), rs358231 (cytosolic ß-glucosidase [CBG]), and rs2273697 (ABCC2) - were determined. RESULTS: We included 102 women. The effects on bone remodeling were similar: rises in vitamin D were significantly associated with reductions in PTH, CTX, and P1NP. Pharmacogenomic analysis of the genotypes showed that, in AT heterozygotes of the CBG1368T>A polymorphism, CTX and P1NP were not reduced. CONCLUSION: Genistein added to calcium and vitamin D supplementation had no additional effect. The supplementation of individual AT heterozygotes of the CBG1368T>A polymorphism had no effect on markers of bone remodeling.

Recomendaciones prácticas para la antisepsia de la piel del paciente antes de cirugía / Practical recommendations for skin preparation of Surgical Site

La búsqueda de estrategias para la disminución de la infección de sitio operatorio (ISO) es una prioridad, dado el impacto que ésta tiene en los resultados de la atención de los pacientes. Recientemente ha tomado gran relevancia en la prevención de la ISO, la preparación prequirúrgica de la piel del paciente como uno de los factores clave, en los que se puede intervenir y disminuir el riesgo. En los últimos años han aparecido revisiones exhaustivas dedicadas no solo a la comparación de las soluciones antisépticas, y técnica de aplicación, también acerca de la importancia del baño pre operatorio, uso de cintas y compresas quirúrgicas impregnadas con antisépticos y el recorte de cabello preoperatorio. En esta publicación se describen los hallazgos más importantes relacionados con la preparación antiséptica de la piel del paciente y se propone un protocolo con recomendaciones prácticas para ser implementado en las instituciones del país. Se incluyen recomendaciones basadas en niveles de evidencia sobre el uso de las soluciones antisépticas (yodopovidona, clorhexidina, clorhexidina mas alcohol, entre otras) con énfasis en las ventajas y desventajas de cada una de ellas.

The search for strategies for reduction of Surgical Site infection (SSI) is a priority, given the impact that infections have on the outcome of the patients. The preoperative patient skin antisepsis, has recently gained greater significance in the prevention of SSI, as one of the critical factors, which can be intervened and can reduce the risk of infection. In recent years, comprehensive investigations have been published not only dedicated to the comparison of antiseptic solutions, application techniques, but also about the importance of preoperative bathing, use of surgical tapes and dressings impregnated with antiseptics, and preoperative shaving. This review outlines the key findings related to the preoperative patient's skin antisepsis and offers a protocol with practical recommendations to be implemented in the institutions of our country. It provides evidence based recommendations about the use of antiseptic solutions (povidone iodine, chlorhexidine, chlorhexidine plus alcohol, etc.) with emphasis on the advantages and disadvantages of each one.

[Clinical features and toxicity of tuberculosis treatment in patients with cancer]. / Características clínicas y toxicidad del tratamiento de tuberculosis en pacientes con cáncer.

OBJECTIVES: To assess the clinical and epidemiological characteristics of active tuberculosis in patients with malignancy and to assess the influence of TB treatment on cancer management at the National Institute of Neoplastic Diseases from 2008 to 2013. MATERIALS AND METHODS: Observational study of TB cases diagnosed by positive sputum microscopy in patients with cancer. Clinical information, evolution, and pathologic information of neoplasia was reviewed. RESULTS: 76 cases of active tuberculosis after being diagnosed with cancer were found. The median age was 51.3 years. Median follow-up was 2.1 years. The most common cancers were acute lymphocytic leukemia (14.5%), for the hematologic cancers; and cancer of the cervix (14.5%), breast (10.5%), and gastric (7.9%) for non-hematological cancers. 27.6% of patients had recurrence of the tumor; TB diagnosis confounded the initial staging by 6.9% and was initially stated as cancer recurrence in 11.1% (breast and colon cancers). The diagnosis of tuberculosis delayed or influenced the dose reduction of the antineoplastic treatment in 11.1% of the cases (acute lymphocytic leukemia and non-Hodgkin lymphoma). 8.3% of patients had toxicity to the TB treatment. CONCLUSIONS: Cancer patients may have active tuberculosis infection. The interference effect of diagnosis and treatment of tuberculosis on the assessment of cancer and cancer treatment in our series is minimal.

Características cl¡nicas y toxicidad del tratamiento de tuberculosis en pacientes con cáncer / Clinical features and toxicity of tuberculosis treatment in patients with cancer

Objetivos. Evaluar las características clínico-epidemiológicas de la tuberculosis activa en pacientes portadores de neoplasia maligna y evaluar la influencia del tratamiento antituberculoso sobre el manejo de cáncer en el Instituto Nacional de Enfermedades Neoplásicas entre el 2008 y 2013. Materiales y métodos. Estudio observacional de casos de tuberculosis diagnosticados mediante baciloscopía positiva en pacientes con cáncer. Se revisó la información clínica, evolución, e información patológica de la neoplasia. Resultados. Se encontraron 76 casos de tuberculosis activa luego del diagnóstico de cáncer. La mediana de edad fue 51,3 años. La mediana de seguimiento fue 2,1 años. Las neoplasias más frecuentes fueron leucemia linfática aguda (14,5%) para las hematológicas y cáncer de cérvix (14,5%), mama (10,5%) y gástrico (7,9%) para las no hematológicas. El 27,6% de los pacientes presentó recurrencia de la neoplasia; el diagnóstico de tuberculosis confundió el estadiaje inicial en 6,9% y se planteó inicialmente como recurrencia del cáncer en 11,1% (neoplasias de mama y colon). El diagnóstico de tuberculosis retrasó o influyó en la reducción de dosis del tratamiento antineoplásico en 11,1% de los casos (leucemia linfática aguda y linfoma no Hodgkin). El 8,3% de los pacientes presentó toxicidad al tratamiento antituberculoso. Conclusiones. Los pacientes con cáncer pueden presentar infección activa por tuberculosis. El efecto de interferencia del diagnóstico y tratamiento de tuberculosis sobre la evaluación del cáncer y el tratamiento antineoplásico en nuestra serie es mínimo.

Objectives. To assess the clinical and epidemiological characteristics of active tuberculosis in patients with malignancy and to assess the influence of TB treatment on cancer management at the National Institute of Neoplastic Diseases from 2008 to 2013. Materials and methods. Observational study of TB cases diagnosed by positive sputum microscopy in patients with cancer. Clinical information, evolution, and pathologic information of neoplasia was reviewed. Results.76 cases of active tuberculosis after being diagnosed with cancer were found. The median age was 51.3 years. Median follow-up was 2.1 years. The most common cancers were acute lymphocytic leukemia (14.5%), for the hematologic cancers; and cancer of the cervix (14.5%), breast (10.5%), and gastric (7.9%) for non-hematological cancers. 27.6% of patients had recurrence of the tumor; TB diagnosis confounded the initial staging by 6.9% and was initially stated as cancer recurrence in 11.1% (breast and colon cancers). The diagnosis of tuberculosis delayed or influenced the dose reduction of the antineoplastic treatment in 11.1% of the cases (acute lymphocytic leukemia and non-Hodgkin lymphoma). 8.3% of patients had toxicity to the TB treatment. Conclusions. Cancer patients may have active tuberculosis infection. The interference effect of diagnosis and treatment of tuberculosis on the assessment of cancer and cancer treatment in our series is minimal.

U1 adaptors for the therapeutic knockdown of the oncogene pim-1 kinase in glioblastoma.

U1 small nuclear interference (U1i) has recently been described as a novel gene silencing mechanism. U1i employs short oligonucleotides, so-called U1 adaptors, for specific gene knockdown, expanding the field of current silencing strategies that are primarily based on RNA interference (RNAi) or antisense. Despite the potential of U1 adaptors as therapeutic agents, their in vivo application has not yet been studied. Here we explore U1i by analyzing U1 adaptor-mediated silencing of the oncogene Pim-1 in glioblastoma cells. We have generated Pim-1-specific U1 adaptors comprising DNA, locked nucleic acids (LNA), and 2'-O-Methyl RNA and demonstrate their ability to induce a Pim-1 knockdown, leading to antiproliferative and pro-apoptotic effects. For the therapeutic in vivo application of U1 adaptors, we establish their complexation with branched low molecular weight polyethylenimine (PEI). Upon injection of nanoscale PEI/adaptor complexes into subcutaneous glioblastoma xenografts in mice, we observed the knockdown of Pim-1 that resulted in the suppression of tumor growth. The absence of hepatotoxicity and immune stimulation also demonstrates the biocompatibility of PEI/adaptor complexes. We conclude that U1i represents an alternative to RNAi for the therapeutic silencing of pathologically upregulated genes and demonstrate the functional relevance of Pim-1 oncogene knockdown in glioblastoma. We furthermore introduce nanoscale PEI/adaptor complexes as efficient and safe for in vivo application, thus offering novel therapeutic approaches based on U1i-mediated gene knockdown.

Micronutrient status in morbidly obese women before bariatric surgery.

BACKGROUND: A high prevalence of micronutrient deficiencies in obese subjects has been reported. Bariatric surgery is the most effective long-term treatment of morbid obesity, but this treatment can result in secondary micronutrient deficiencies. The aim of our work was to describe the micronutrient status in obese women before surgery at a university hospital. METHODS: We analyzed a consecutive series of 115 women who were referred to our unit for evaluation for bariatric surgery. Their weight, height, body mass index, and waist circumference were measured. The basal hemoglobin, albumin, prealbumin, ferritin, copper, zinc, calcium, phosphorus, parathyroid hormone, and vitamin (A, D, E, K, B12, and folic) blood levels were also determined. RESULTS: Deficiencies were found in 6.1% of the subjects for albumin, 21.7% for prealbumin, 2.6% for hemoglobin, and 5.2% for ferritin. In the vitamin analysis, no deficiencies were found in the patients for vitamins A, E, or K, but 71.3% had a moderate deficiency of vitamin D and 26.1% a severe deficiency of vitamin D (<15 ng/mL). In concorndance with the high prevalence of 25-OH vitamin D deficiency, 22.6% of the patients had secondary hyperparathyroidism with intact parathyroid hormone levels >72 pg/mL. Deficiencies were found in 9.5% for vitamin B12, 25.2% for folic acid, 67.8% for copper, and 73.9% for zinc. CONCLUSION: Our study has demonstrated a high prevalence of micronutrient deficiencies in morbidly obese women seeking obesity surgery.

Zinc and copper serum levels of morbidly obese patients before and after biliopancreatic diversion: 4 years of follow-up.

BACKGROUND: Zinc and copper are two essential trace elements. However, few studies have been conducted specifically to investigate these deficiencies in patients who underwent bariatric surgery. The aim of our work was to describe the influence of biliopancreatic diversion (BPD) on serum copper and zinc levels during 4 years. METHODS: We have analyzed a consecutive series of 65 patients who have been followed-up for 4 years after undergoing open BPD. RESULTS: The final (4 years) initial excess weight percent loss was 63.5%. A significant improvement of BMI, weight, waist circumference, and fat mass was detected. The preoperative average zinc (42.2 ± 53.2 µg/dl) and copper (61.3 ± 58.6 µg/dl) levels are under the lower limit of the normal values. These data show a deficient micronutrient status in morbidly obese patients, 73.8% of patients had low basal zinc values and 67.8% low basal copper values. Values of both micronutrients at different times (6 months, 1, 2, 3, and 4 years) were lower than basal value. CONCLUSION: BPD is an effective method of sustainable weight loss. Otherwise, a high prevalence of zinc and copper basal deficiencies in morbidly obese seeking bariatric surgery was detected. These deficiencies of copper and zinc increased during the 4 years of follow-up after BDP.

Influence of lys656asn polymorphism of leptin receptor gene on surgical results of biliopancreatic diversion.

BACKGROUND: Bariatric surgery is the most effective long-term treatment for morbid obesity, reducing obesity-associated comorbidities. The purpose of the present study was to evaluate Lys656Asn polymorphism of leptin receptor gene on outcomes 1 year after biliopancreatic diversion. METHODS: A sample of 41 morbidly obese patients (body mass index (BMI) > 40 kg/m(2)) were operated on. Biochemical and anthropometric evaluation were realized at basal visit and at each visit. The frequency of patients with diabetes mellitus, hypertension, and hyperlipidemia was recorded at each visit. RESULTS: Thirty-two patients (78%) had genotype Lys656/Lys656, eight patients (19.5%) Lys656/Asn656 genotype, and one patient (2.4%) Asn656/Asn656 genotype. In the wild-type group, body mass index, weight, glucose, total cholesterol, LDL cholesterol, triacylglycerol, and systolic blood pressure decreased. In the mutant group, the same parameters improved. Initial weight percent loss at 1 year of follow-up was higher in mutant group than in wild-type group (38.9% vs 29.9%; p < 0.05). Total weight loss was higher in mutant group than wild-type group (50.7 vs 37.2 kg; p < 0.05). Basal weight and BMI were higher in mutant group than wild type. CONCLUSION: Weight loss was higher in mutant group (Lys656Asn and Asn656Asn) than wild-type group (Lys656Lys) after bariatric surgery. Carriers of the allelic variant (Asn) had higher basal weight.