ROR2 increases the chemoresistance of melanoma by regulating p53 and Bcl2-family proteins via ERK hyperactivation.

BACKGROUND: ROR2 is a tyrosine-kinase receptor whose expression is dysregulated in many human diseases. In cancer, ROR2 stimulates proliferation, survival, migration, and metastasis, and is associated with more aggressive tumor stages. The purpose of this work is to study the role of ROR2 in the chemoresistance of melanoma. METHODS: Gain- and loss-of-function experiments were used to study the biological function of ROR2 in melanoma. Cell death induced by chemotherapeutic drugs and BH-3 mimetics was evaluated using crystal violet cytotoxicity assays and annexin V/propidium iodide staining. Western blots were used to evaluate the expression of proteins implicated in cell death. The differences observed between cells with manipulation of ROR2 levels and control cells were evaluated using both Student's t-test and ANOVA. RESULTS: We describe that ROR2 contributes to tumor progression by enhancing the resistance of melanoma cells to both chemotherapeutic drugs and BH-3 mimetics. We demonstrate that ROR2 reduced cell death upon treatment with cisplatin, dacarbazine, lomustine, camptothecin, paclitaxel, ABT-737, TW-37, and venetoclax. This effect was mediated by the inhibition of apoptosis. In addition, we investigated the molecular mechanisms implicated in this role of ROR2. We identified the MDM2/p53 pathway as a novel target of ROR2 since ROR2 positively regulates MDM2 levels, thus leading to p53 downregulation. We also showed that ROR2 also upregulates Mcl-1 and Bcl2-xL while it negatively regulates Bax and Bid expression. The effect of ROR2 on the expression of these proteins is mediated by the hyperactivation of ERK. CONCLUSIONS: These results demonstrate that ROR2 contributes to melanoma progression by inhibiting apoptosis and increasing chemoresistance. These results not only position ROR2 as a marker of chemoresistance but also support its use as a novel therapeutic target in cancer.

ROR2 has a protective role in melanoma by inhibiting Akt activity, cell-cycle progression, and proliferation.

BACKGROUND: Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a Wnt5a receptor aberrantly expressed in cancer that was shown to either suppress or promote carcinogenesis in different tumor types. Our goal was to study the role of ROR2 in melanoma. METHODS: Gain and loss-of-function strategies were applied to study the biological function of ROR2 in melanoma. Proliferation assays, flow cytometry, and western blotting were used to evaluate cell proliferation and changes in expression levels of cell-cycle and proliferation markers. The role of ROR2 in tumor growth was assessed in xenotransplantation experiments followed by immunohistochemistry analysis of the tumors. The role of ROR2 in melanoma patients was assessed by analysis of clinical data from the Leeds Melanoma Cohort. RESULTS: Unlike previous findings describing ROR2 as an oncogene in melanoma, we describe that ROR2 prevents tumor growth by inhibiting cell-cycle progression and the proliferation of melanoma cells. The effect of ROR2 is mediated by inhibition of Akt phosphorylation and activity which, in turn, regulates the expression, phosphorylation, and localization of major cell-cycle regulators including cyclins (A, B, D, and E), CDK1, CDK4, RB, p21, and p27. Xenotransplantation experiments demonstrated that ROR2 also reduces proliferation in vivo, resulting in inhibition of tumor growth. In agreement with these findings, a higher ROR2 level favors thin and non-ulcerated primary melanomas with reduced mitotic rate and better prognosis. CONCLUSION: We conclude that the expression of ROR2 slows down the growth of primary tumors and contributes to prolonging melanoma survival. Our results demonstrate that ROR2 has a far more complex role than originally described.

ROR2 promotes epithelial-mesenchymal transition by hyperactivating ERK in melanoma.

Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a protein with important functions during embryogenesis that is dysregulated in human cancer. An intriguing feature of this receptor is that it plays opposite roles in different tumor types either promoting or inhibiting tumor progression. Understanding the complex role of this receptor requires a more profound exploration of both the altered biological and molecular mechanisms. Here, we describe that ROR2 promotes Epithelial-Mesenchymal Transition (EMT) by inducing cadherin switch and the upregulation of the transcription factors ZEB1, Twist, Slug, Snail, and HIF1A, together with a mesenchymal phenotype and increased migration. We show that ROR2 activates both p38 and ERK mitogen-activated protein kinase pathways independently of Wnt5a. Further, we demonstrated that the upregulation of EMT-related proteins depends on the hyperactivation of the ERK pathway far above the typical high constitutive activity observed in melanoma. In addition, ROR2 also promoted ERK phosphorylation, EMT, invasion, and necrosis in xenotransplanted mice. ROR2 also associates with EMT in tumor samples from melanoma patients where analysis of large cohorts revealed that increased ROR2 levels are linked to EMT signatures. This important role of ROR2 translates into melanoma patient' s prognosis since elevated ROR2 levels reduced overall survival and distant metastasis-free survival of patients with lymph node metastasis. In sum, these results demonstrate that ROR2 contributes to melanoma progression by inducing EMT and necrosis and can be an attractive therapeutic target for melanoma.

Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability.

Recent studies have described a DNA damage tolerance pathway choice that involves a competition between PrimPol-mediated repriming and fork reversal. Screening different translesion DNA synthesis (TLS) polymerases by the use of tools for their depletion, we identified a unique role of Pol ι in regulating such a pathway choice. Pol ι deficiency unleashes PrimPol-dependent repriming, which accelerates DNA replication in a pathway that is epistatic with ZRANB3 knockdown. In Pol ι-depleted cells, the excess participation of PrimPol in nascent DNA elongation reduces replication stress signals, but thereby also checkpoint activation in S phase, triggering chromosome instability in M phase. This TLS-independent function of Pol ι requires its PCNA-interacting but not its polymerase domain. Our findings unravel an unanticipated role of Pol ι in protecting the genome stability of cells from detrimental changes in DNA replication dynamics caused by PrimPol.

Cellular and molecular mechanisms implicated in the dual role of ROR2 in cancer.

ROR1 and ROR2 are Wnt receptors that are critical for ß-catenin-independent Wnt pathways and have been linked to processes driving tumor progression, such as cell proliferation, survival, invasion, and therapy resistance. Both receptors have garnered interest as potential therapeutic targets since they are largely absent in adult tissue, are overexpressed in several cancers, and, as members of the receptor tyrosine kinase family, are easier to target than all other components of the pathway. Unlike ROR1 which always promotes tumorigenesis, ROR2 has a very complex role in cancer acting either to promote or inhibit tumor progression in different tumor types. In the present article, we summarize the findings on ROR2 expression in cancer patients and its impact on clinical outcome. Further, we review the biological processes and signaling pathways regulated by ROR2 that explain its dual role in cancer. Finally, we describe the ongoing strategies to target ROR2 in cancer.

Bioinformatic analysis identifies epidermal development genes that contribute to melanoma progression.

Several diagnostic and prognostic markers for melanoma have been identified in last few years. However, their actual contribution to melanoma progression have not been investigated in detail. This study was aimed to identify genes, biological processes, and signaling pathways implicated in melanoma progression by applying bioinformatics analysis. We identified nine differentially expressed genes (DEGs) (IL36RN, KRT6A, KRT6B, KRT16, S100A7, SPRR1A, SPRR1B, SPRR2B, and KLK7) that were upregulated in primary melanoma compared with metastatic melanoma in all five datasets analyzed. All these genes except IL36RN, both form a protein-protein interaction network and have cellular functions associated with constitutive processes of keratinocytes. Thus, they were generically termed Epidermal Development and Cornification (EDC) genes. The differential expression of these genes in primary and metastatic melanoma was confirmed in the TCGA-SKCM cohort. High expression of the EDC genes correlated with reduced tumor thickness in primary melanoma and shorter survival in metastatic melanoma. Analysis of DEGs from primary melanoma patients displaying high or low expression of all eight EDC revealed that the upregulated genes are enriched in biological process related to cell migration, extracellular matrix organization, invasion, and Epithelial-Mesenchymal Transition. Further analysis of enriched curated oncogenic genesets together with RPPA data of phosphorylated proteins revealed the activation of MEK, ATF2, and EGFR pathways in tumors displaying high expression of EDC genes. Thus, EDC genes may contribute to melanoma progression by promoting the activation of MEK, ATF2, and EGFR pathways together with biological processes associated with tumor aggressiveness.

Bcl-2-like protein-10 increases aggressive features of melanoma cells.

Aim: B-cell lymphoma-2 (Bcl-2)-like protein-10 (Bcl2L10) is the less studied member of Bcl-2 family proteins, with the controversial role in different cancer histotypes. Very recently, Bcl2L10 expression in melanoma tumor specimens and its role in melanoma response to therapy have been demonstrated. Here, the involvement of Bcl2L10 on the in vitro and in vivo properties associated with melanoma aggressive features has been investigated. Methods: Endogenous Bcl2L10 protein expression was detected by western blotting analysis in a panel of patient-derived and commercially available human melanoma cells. In vitro assays to evaluate clonogenicity, cell proliferation, cell migration, cell invasion, and in vitro capillary-like structure formation [vasculogenic mimicry (VM)] have been performed by using human melanoma cells stably overexpressing Bcl2L10 or transiently transfected for loss/gain function of Bcl2L10, grown under two- or three-dimensional (3D) conditions Xenograft melanoma model was employed to evaluate in vivo tumor growth and angiogenesis. Results: Results demonstrated that Bcl2L10 acts as an inducer of in vitro cell migration, invasion, and VM, while in vitro cell proliferation, in vivo tumor growth, as well as colony formation properties were not affected. Dissecting different signaling pathways, it was found that Bcl2L10 positively affects the phosphorylation of extracellular-signal-regulated kinase (ERK) and the expression of markers of cell invasion, such as urokinase plasminogen activator receptor (uPAR) and matrix metalloproteinases (MMPs). Of note, Bcl2L10-dependent in vitro migration, invasion, and VM are linked to uPAR. Bcl2L10 also negatively regulates the intracellular calcium level. Finally, reduced invasion capability in 3D spheroid invasion assay of melanoma cells transiently overexpressing Bcl2L10 was observed after treatment with inhibitors of MMPs and uPAR. Conclusions: Overall, data reported in this paper provide evidence supporting a positive role of Bcl2L10 in melanoma aggressive features.

[Progress on the Millenium Development Goals 4 and 5 in Mesoamerica]. / Avances en los Objetivos de Desarrollo del Milenio 4 y 5 en Mesoamérica.

OBJECTIVES: To describe the advances made by countries in the Mesoamerican region towards reaching Millenium Development Goals (MDG) 4 and 5, and discuss the most useful tasks to help the region in accomplishing or keeping track of these objectives. MATERIAL AND METHODS: The trend estimates of maternal and under 5 mortality from 1990 to 2008, the effective coverage of vaccination against diphteria, pertussis and tetanus (DPT), prenatal care and childbirth by qualified personnel were taken from the Institute of Health Metrics and Evaluation (IHME) and the causes of death for children under five were taken from the Children's Health Epidemiology Reference Group of WHO (CHERG). RESULTS: The regional trend in the rate of mortality for children under five (MDG-4) in the last 18 years shows an annual reduction of 4.2%, significantly above the global reduction of 2.1%. This suggests that countries of Mesoamerica will be able to fulfill this objective. In contrast, data for 2008 shows that the rate of reduction of maternal mortality is very heterogeneous and it is unlikely that any of the countries in the region will reach this goal. CONCLUSION: Efforts made by countries in Mesoamerica have been substantial in controlling mortality in children under five years but insufficient to achieve MDG-5. Although the tendency is in the right track the reduction rate will only partially fulfill the acquired commitments to eradicate poverty.

Ki-67 Proliferative Activity in the Tumor Margins as a Robust Prognosis Factor in Glioblastoma Patients.

INTRODUCTION: The infiltrative margin of glioblastomas (GBM) contains proliferative tumor cells difficult to estimate radiologically as they are included in the hyperintense signal of T2 sequences and they remain in the cavity margin after tumor resection. The amount of these cells could determine overall survival (OS) of these patients. MATERIAL AND METHODS: From October 2007 to January 2010, patients whose MRI were suggestive of newly diagnosed, resectable high-grade glioma were operated using fluorescence-guided surgery (FGS). Separate samples were selectively taken from nonfluorescent white matter areas just adjacent to the border of the pale fluorescence and staining was made for Ki-67. OS was analyzed with Kaplan-Meier and Cox regression. Multivariate analysis included the following prognosis variables: age, extent of resection (EOR), O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and performance status index. RESULTS: Sample included 65 patients, comprising 37 men and 28 women, with a median Karnofsky Performance Score (KPS) of 80 (40-100) and mean age of 60 (34-78) years. Mean preoperative tumor volume was 35.8 mL. EOR was 100% in 52 patients (80%), with the lower EOR being 88%. For Ki-67, 39 patients had <5% and 26 had ≥5%. OS was 26.8 months (95% confidence interval [CI]: 18.9-28.2) for the Ki-67 low group versus 15.8 months (95% CI: 7.7-18.2) for the Ki-67 high group (p = 0.002). CONCLUSION: Proliferative activity in the normal-looking brain around the resection cavity measured with Ki-67 immunostaining is an important independent prognostic factor for GBM cases with complete resection of enhancing tumor. When complete resection is not reached, this factor is not relevant for prognosis.

BCL2L10 Is Overexpressed in Melanoma Downstream of STAT3 and Promotes Cisplatin and ABT-737 Resistance.

The anti-apoptotic proteins from the Bcl-2 family are important therapeutic targets since they convey resistance to anticancer regimens. Despite the suspected functional redundancy among the six proteins of this subfamily, both basic studies and therapeutic approaches have focused mainly on BCL2, Bcl-xL, and MCL1. The role of BCL2L10, another member of this group, has been poorly studied in cancer and never has been in melanoma. We describe here that BCL2L10 is abundantly and frequently expressed both in melanoma cell lines and tumor samples. We established that BCL2L10 expression is driven by STAT3-mediated transcription, and by using reporter assays, site-directed mutagenesis, and ChIP analysis, we identified the functional STAT3 responsive elements in the BCL2L10 promoter. BCL2L10 is a pro-survival factor in melanoma since its expression reduced the cytotoxic effects of cisplatin, dacarbazine, and ABT-737 (a BCL2, Bcl-xL, and Bcl-w inhibitor). Meanwhile, both genetic and pharmacological inhibition of BCL2L10 sensitized melanoma cells to cisplatin and ABT-737. Finally, BCL2L10 inhibited the cell death upon combination treatments of PLX-4032, a BRAF inhibitor, with ABT-737 or cisplatin. In summary, we determined that BCL2L10 is expressed in melanoma and contributes to cell survival. Hence, targeting BCL2L10 may enhance the clinical efficacy of other therapies for malignant melanoma.

Histological healing outcomes at the bone-titanium interface of loaded and unloaded dental implants placed in humans: A systematic review of controlled clinical trials.

Purpose: The purpose of this systematic review was to assess the histological healing outcomes at the bone­titanium interface of loaded and unloaded dental implants placed in humans. Materials and methods: An electronic search was conducted using the PubMed, Embase and Cochrane Central Register of Controlled Trials (Central) databases up to and including April 2020 to identify clinical trials reporting human histological data of bone healing around titanium dental implants placed in healed alveolar ridges. The search was conducted by two independent reviewers with no language restrictions. The risk of bias of each included study was assessed using the Cochrane Collaboration's domain-based, two-part tool. Results: Of the 4564 potentially eligible articles, only 25 were included in this systematic review (13 randomised and 12 controlled clinical trials), with a total of 548 micro/transitional implants evaluated. The marked heterogeneity between studies did not allow the data to be combined for meta-analyses. In general, based on mean values of bone-to-implant contact (range 9% to 73%), bone density outside the threaded area (range 14.9% to 31.6%), bone density in the threaded area (range 17.9% to 56.9%) and osteocyte index (range 19.79 to 37.88 cells/mm2), all implant surface modifications demonstrated osseointegration potential. Furthermore, immediate loading was related to higher bone-to-implant contact, bone density outside the threaded area and osteocyte index; longer healing periods to higher bone-to-implant contact; and smoking to lower bone-to-implant contact, bone density in the threaded area and bone density outside the threaded area. Conclusions: Despite the fact that several modifications were made to the implant surface, when considering the values for bone-to-implant contact, bone density in the threaded area, bone density outside the threaded area and osteocyte index, machined surfaces showed the worst healing outcomes. Nevertheless, osseointegration was improved by both immediate loading and longer healing periods and worsened by smoking.

An Autocrine Wnt5a Loop Promotes NF-κB Pathway Activation and Cytokine/Chemokine Secretion in Melanoma.

Wnt5a signaling has been implicated in the progression of cancer by regulating multiple cellular processes, largely migration and invasion, epithelial-mesenchymal transition (EMT), and metastasis. Since Wnt5a signaling has also been involved in inflammatory processes in infectious and inflammatory diseases, we addressed the role of Wnt5a in regulating NF-κB, a pivotal mediator of inflammatory responses, in the context of cancer. The treatment of melanoma cells with Wnt5a induced phosphorylation of the NF-κB subunit p65 as well as IKK phosphorylation and IκB degradation. By using cDNA overexpression, RNA interference, and dominant negative mutants we determined that ROR1, Dvl2, and Akt (from the Wnt5a pathway) and TRAF2 and RIP (from the NF-κB pathway) are required for the Wnt5a/NF-κB crosstalk. Wnt5a also induced p65 nuclear translocation and increased NF-κB activity as evidenced by reporter assays and a NF-κB-specific upregulation of RelB, Bcl-2, and Cyclin D1. Further, stimulation of melanoma cells with Wnt5a increased the secretion of cytokines and chemokines, including IL-6, IL-8, IL-11, and IL-6 soluble receptor, MCP-1, and TNF soluble receptor I. The inhibition of endogenous Wnt5a demonstrated that an autocrine Wnt5a loop is a major regulator of the NF-κB pathway in melanoma. Taken together, these results indicate that Wnt5a activates the NF-κB pathway and has an immunomodulatory effect on melanoma through the secretion of cytokines and chemokines.

STAT3 enhances the constitutive activity of AGC kinases in melanoma by transactivating PDK1.

BACKGROUND: The PI3K/Akt and the STAT3 pathways are functionally associated in many tumor types. Both in vitro and in vivo studies have revealed that either biochemical or genetic manipulation of the STAT3 pathway activity induce changes in the same direction in Akt activity. However, the implicated mechanism has been poorly characterized. Our goal was to characterize the precise mechanism linking STAT3 with the activity of Akt and other AGC kinases in cancer using melanoma cells as a model. RESULTS: We show that active STAT3 is constitutively bound to the PDK1 promoter and positively regulate PDK1 transcription through two STAT3 responsive elements. Transduction of WM9 and UACC903 melanoma cells with STAT3-small hairpin RNA decreased both PDK1 mRNA and protein levels. STAT3 knockdown also induced a decrease of the phosphorylation of AGC kinases Akt, PKC, and SGK. The inhibitory effect of STAT3 silencing on Akt phosphorylation was restored by HA-PDK1. Along this line, HA-PDK1 expression significantly blocked the cell death induced by dacarbazine plus STAT3 knockdown. This effect might be mediated by Bcl2 proteins since HA-PDK1 rescued Bcl2, Bcl-XL, and Mcl1 levels that were down-regulated upon STAT3 silencing. CONCLUSIONS: We show that PDK1 is a transcriptional target of STAT3, linking STAT3 pathway with AGC kinases activity in melanoma. These data provide further rationale for the ongoing effort to therapeutically target STAT3 and PDK1 in melanoma and, possibly, other malignancies.

Avances en los Objetivos de Desarrollo del Milenio 4 y 5 en Mesoamérica / Progress on the Millenium Development Goals 4 and 5 in Mesoamerica

OBJETIVOS: Presentar los avances realizados en la región mesoamericana en relación con los Objetivos de Desarrollo del Milenio 4 y 5 por medio de su análisis y discutir las intervenciones más relevantes para ayudar en el logro de estos objetivos o, por lo menos, en mantener su trayectoria. MATERIAL Y MÉTODOS: Se utilizaron como fuentes las estimaciones de 1990-2008 sobre mortalidad en menores de cinco años y materna, las coberturas de vacunación contra difteria, tétanos y tosferina (DTP), atención prenatal y atención del parto por personal calificado, realizadas por el Instituto de la Métrica y Evaluación en Salud y las causas de mortalidad en menores de cinco años, realizadas por el Grupo de Referencia sobre Epidemiología y Salud en la Infancia de la OMS (CHERG). RESULTADOS: La tendencia de la tasa de mortalidad de menores de cinco años (ODM-4) muestra una reducción anual de 4.2% en los últimos 18 años, comparada con la reducción global de 2.1%. En contraste, la tasa de descenso de la mortalidad materna (ODM-5) es muy heterogénea y ninguno de los países de la región alcanzará este objetivo. CONCLUSIÓN: Los esfuerzos realizados por los países en Mesoamérica han sido sustantivos en la reducción de mortalidad en menores de cinco años; sin embargo no han sido suficientes para alcanzar la meta programada por el ODM-5. Aunque la tendencia es correcta, el ritmo de descenso cumplirá parcialmente con los compromisos adquiridos para erradicar la pobreza.

OBJECTIVES: To describe the advances made by countries in the Mesoamerican region towards reaching Millenium Development Goals (MDG) 4 and 5, and discuss the most useful tasks to help the region in accomplishing or keeping track of these objectives. MATERIAL AND METHODS: The trend estimates of maternal and under 5 mortality from 1990 to 2008, the effective coverage of vaccination against diphteria, pertussis and tetanus (DPT), prenatal care and childbirth by qualified personnel were taken from the Institute of Health Metrics and Evaluation (IHME) and the causes of death for children under five were taken from the Children's Health Epidemiology Reference Group of WHO (CHERG). RESULTS: The regional trend in the rate of mortality for children under five (MDG-4) in the last 18 years shows an annual reduction of 4.2%, significantly above the global reduction of 2.1%. This suggests that countries of Mesoamerica will be able to fulfill this objective. In contrast, data for 2008 shows that the rate of reduction of maternal mortality is very heterogeneous and it is unlikely that any of the countries in the region will reach this goal. CONCLUSION: Efforts made by countries in Mesoamerica have been substantial in controlling mortality in children under five years but insufficient to achieve MDG-5. Although the tendency is in the right track the reduction rate will only partially fulfill the acquired commitments to eradicate poverty.

Cobertura efectiva de las intervenciones en salud de América Latina y el Caribe: métrica para evaluar los sistemas de salud / Effective coverage of health interventions in Latin America and the Caribbean: metrics for the assessment of health systems performance

OBJETIVO: Medir la cobertura efectiva para once intervenciones de salud en nueve países de América Latina utilizando las encuestas de demografía y salud o registros administrativos que abarcan la salud infantil, de la mujer y el adulto. MATERIAL Y MÉTODOS: Se seleccionaron las intervenciones y se armonizaron definiciones y métodos de cálculo de acuerdo con la información disponible para lograr la comparabilidad entre países. RESULTADOS: Chile es el país con mejores indicadores de coberturas crudas y efectivas, seguido por México y Colombia, y existen brechas importantes entre regiones, departamentos o estados. CONCLUSIONES: La métrica de cobertura efectiva es un indicador sensible que relaciona la necesidad de las intervenciones en salud, su utilización y calidad, lo que permite valorar los programas de salud al aportar datos precisos de dónde y a quién deben dirigirse los recursos y esfuerzos nacionales para que los países alcancen los propósitos y metas planteados.

OBJECTIVE: To measure effective coverage for ll health interventions in Latin America including the children's, women's and adult health, as part of program evaluation. MATERIAL AND METHODS: Interventions were selected; the definitions and calculation methods were harmonized according to the information available to ensure comparability between countries. RESULTS: Chile has better indicators of crude and effective coverage followed by Mexico and Colombia.There are significant gaps between regions, counties or states. CONCLUSIONS: The health metric on effective coverage is a sensitive indicator that links three important aspects: Coverage of health interventions, use of health services, and access to such services. Effective coverage is a good tool to evaluate health programs performance, and also provides data of where and to whom the system should address national efforts and resources to achieve the purposes and goals set.

Factores de riesgo asociados a complicaciones intrahospitalarias en adultos mayores del Hospital Nacional Edgardo Rebagliati Martins Lima, 2010 / Risk factors associated with nosocomial complications in older adults the National Hospital Edgardo Rebagliati Martins de Lima, 2010

La prolongación de la esperanza de vida; la prevalencia de enfermedades crónicas; los cambios fisiológicos que ocurren en el envejecimiento; el deterioro del estado funcional; y el uso frecuente de los servicios hospitalarios, exponen a los adultos mayores a complicaciones intrahospitalarias. Por esta razón se propone determinar los principales factores de riesgo asociados a complicaciones intrahospitalarias en adultos mayores del Hospital Nacional Edgardo Rebagliati Martins, Lima. Material y Métodos: Se diseñó un estudio de casos y controles pareados (2:1); Casos: adultos mayores con complicaciones intrahospitalarias, registrados en el sistema de vigilancia epidemiológica activa, definidas con criterios del Centro de Control de Enfermedades (CDC); durante noviembre del 2010 a febrero del 2011 y como controles: adultos mayores, sin complicaciones intrahospitalarias registrados en el sistema de gestión hospitalaria. Se aplicó una encuesta estructurada que! incluyó, factores de comorbilidad previa (índice de Charlson) y el estado funcional basal y la pérdida funcional durante la hospitalización (índice de Barthel); y las complicaciones intrahospitalarias más frecuentes acorde a definiciones del Centro de Control de Enfermedades. Resultados: Se evaluó 228 adultos mayores (76 casos y 152 controles). Los principales factores de riesgo asociados encontrados en modelo de regresión logística múltiple fueron cáncer (OR: 44,45; IC: 12,5-175,10), enfermedad pulmonar obstructiva crónica (OR:9,51; IC:3,10-29,16), enfermedad arterial periférica (OR:7,57; IC: 2,24-25,58), diabetes (OR:5,1886; IC:12,5-157,10), insuficiencia cardíaca OR:4,5931; IC:1,2971-16,26), deterioro del estado funcional basal (OR:10,20; IC:2,31- 44,93) y carga total de comorbilidad (OR:17,08; IC:1,52-191,70). Los otros factores (demencia, insuficiencia renal crónica, enfermedades cerebro vasculares y la pérdida funcional durante la hospitalización), no tuvieron significación estadística...

The prolongation of life expectancy; the prevalence of chronic diseases; the physiological changes that occur in aging; deterioration in functional status; and frequent use of hospital services; expose older adults to hospital complications. We want to identify the main risk factors associated with hospital complications in older adults in Edgardo Rebagliati Martins National Hospital, Lima. Material and Methods: A matched case controls study (2: 1) was designed; Cases: older adults with hospital complications, registered in the system of active surveillance, defined criteria of the Center for Disease Control (CDC); during November 2010 to February 2011 and as controls: seniors, no hospital complications recorded at the hospital management system. A structured questionnaire that included factors prior comorbidity (Charlson index) and baseline functional status and functional loss during hospitalization (Barthel) was applied; and frequently chord definitions of the Center for Disease Control hospital complications. Results: 228 older adults (76 cases and 152 controls) .The main risk factors associated found in multiple logistic regression model were cancer (OR: 44.45 CI 12.5 to 175.10), chronic obstructive pulmonary disease (OR: 9.51, CI 3.10 to 29.16), peripheral arterial disease (OR: 7.57, CI: 2.24 to 25.58), diabetes (OR = 5.1886; IC : 12.5 to 157.10), heart failure (OR: 4.5931 CI: 1.2971 to 16.26), impaired baseline functional status (OR: 10.20; CI: 2,31 to 44.93) and total burden of comorbidity (OR; 17.08; CI 1.52 to 191.70). The other factors (dementia, chronic renal failure, cerebrovascular disease and functional decline during hospitalization), had no statistical significance...