Association of CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T Polymorphisms with Tacrolimus Dose, Serum Concentration, and Biochemical Parameters in Mexican Patients with Kidney Transplant.

Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. METHODS: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. RESULTS: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13-21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54-93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79-88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. CONCLUSION: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity.

Celecoxib Decreases the Need for Rescue Analgesics after Total Knee Arthroplasty: A Meta-Analysis.

This systematic review and meta-analysis aimed to evaluate the analgesic efficacy and adverse effects of celecoxib after total knee arthroplasty. Keywords in the PubMed and Scopus databases were used to find article abstracts. Each included clinical trial was assessed using the Cochrane Collaboration risk of bias tool, and we extracted data on postoperative pain assessment using the Visual Analogue Scale (VAS) at rest, ambulation, and active range of motion, rescue analgesic intake, and adverse effects. Inverse variance tests with mean differences were used to analyze the numerical variables. The Mantel-Haenszel statistical method and the odds ratio were used to evaluate the dichotomous data. According to this qualitative assessment (n = 482), two studies presented conclusions in favor of celecoxib (n = 187), one showed similar results between celecoxib and the placebo (n = 44), and three clinical trials did not draw conclusions as to the effectiveness of celecoxib versus the placebo (n = 251). Moreover, the evaluation of the rescue analgesic intake showed that the patients receiving celecoxib had a lower intake compared to patients receiving a placebo (n = 278, I2 = 82%, p = 0.006, mean difference = -6.89, 95% IC = -11.76 to -2.02). In conclusion, the pooled analysis shows that administration of celecoxib alone results in a decrease in rescue analgesic consumption compared to a placebo after total knee surgery.

Role of Incretins in Muscle Functionality, Metabolism, and Body Composition in Breast Cancer: A Metabolic Approach to Understanding This Pathology.

A poorly studied issue in women with breast cancer is the role of incretins (GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1)) in the quantity and quality of muscle mass in lean and obese individuals. The current report aims to analyze the patterns of association and the role of incretin in muscle functionality and body composition in women with cancer compared with healthy women (mammography BI-RADS I or II) to elucidate whether GIP and GLP-1 can be used to estimate the risk, in conjunction with overweight or obesity, for breast cancer. We designed a case-control study in women with a breast cancer diagnosis confirmed by biopsy in different clinical stages (CS; n = 87) and healthy women with a mastography BI-RADS I or II within the last year (n = 69). The women were grouped according to body mass index (BMI): lean (<25 kg/m2BS), overweight (≥25-<30 kg/m2BS), and obese (≥30 kg/m2BS). We found that GLP-1 and GIP levels over 18 pg/mL were associated with a risk of breast cancer (GIP OR = 36.5 and GLP-1 OR = 4.16, for the entire sample), particularly in obese women (GIP OR = 8.8 and GLP-1 OR = 6.5), and coincidentally with low muscle quality indexes, showed an association between obesity, cancer, incretin defects, and loss of muscle functionality.

Phase Angle in Head and Neck Cancer: A Sex-Differential Analysis from Biological and Clinical Behavior to Health-Related Quality of Life.

Head and neck cancer (H&NC) is a diverse category of tumors related to malignancies in the common aerodigestive pathway, with high metabolic rate, poor nutritional and treatment outcomes, and elevated mortality despite the best standard treatment. Herein, we focus on determining how the phase angle (PA) differs across sex as a predictor of poor prognosis, low quality-of-life (QoL) scores, and mortality in patients with head and neck cancer. This follow-up study presents a sex-differential analysis in a prospective cohort of 139 head and neck cancer patients categorized by sex as male (n = 107) and female (n = 32). Patients were compared in terms of nutritional, biochemical, and quality-of-life indicators between low and normal PA in women (<3.9° (n = 14, 43.75%) and ≥3.9°) and men (<4.5° (n = 62, 57.9%) and ≥4.5°). Our results show that most patients were in locally advanced clinical stages (women: n = 21 (65.7%); men: n = 67 (62.6%)) and that patients with low PA had a lower punctuation in parameters such as handgrip strength, four-meter walking speed, albumin, C-reactive protein (CRP), and CRP/albumin ratio (CAR), as well as the worst QoL scores in functional and symptomatic scales in both the male and female groups. A comparison between sexes revealed significant disparities; malnourishment and tumor cachexia related to an inflammatory state was more evident in the women's group.

Phase Angle and Nutritional Status: The Impact on Survival and Health-Related Quality of Life in Locally Advanced Uterine Cervical Cancer.

The phase angle, an indicator of muscle mass status and membrane cell integrity, has been associated with low survival, poorer clinical outcomes, and worse quality of life among cancer patients, but information on women with uterine cervical cancer (UCCa) is scarce. In this prospective study, we used a bioelectrical impedance analyzer to obtain the PA of 65 women with UCCa. We compared the health-related quality of life and inflammatory and nutritional indicators between low PA and normal PA. The mean age was 52 ± 13. The low PA and normal PA groups differed in terms of the C-reactive protein (15.8 ± 19.6 versus 6.82 ± 5.02, p = 0.022), glucose (125.39 ± 88.19 versus 88.78 ± 23.08, p = 0.021), albumin (3.9 ± 0.39 versus 4.37 ± 0.30, p = 0.000), EORTC QLQ-C30 loss of appetite symptom scale score (33.33 (0.0-100.00) versus 0.0 (0.0-0.0), p = 0.005), and EORTC QLQ-CX24 menopausal symptoms scale score (0.0 (0.0-33.33) versus 0.0 (0.0-100.0), p = 0.03). The main finding of the present study is the interaction between PA and obesity as critical cofactors in the UCCa adeno and adenosquamous histologic variants, to a greater extent than cervical squamous cell carcinoma.

Phase Angle, a Cornerstone of Outcome in Head and Neck Cancer.

In patients with head and neck cancer, malnutrition is common. Most cases are treated by chemo-radiotherapy and surgery, with adverse effects on the aerodigestive area. Clinical and biochemical characteristics, health-related quality of life, survival, and risk of death were studied. The selected subjects were divided into normal- and low-phase-angle (PA) groups and followed up for at least two years. Mean ages were 67.2 and 59.3 years for low and normal PA, respectively. Patients with PA < 4.42° had significant differences in age, anthropometric and biochemical indicators of malnutrition, and inflammatory status compared to patients with PA > 4.42°. Statistical differences were found in the functional and symptom scales, with lower functional scores and higher symptom scores in patients with low PA. Median survival was 19.8 months for those with PA < 4.42° versus 34.4 months for those with PA > 4.42° (p < 0.001).The relative risk of death was related to low PA (2.6; p < 0.001). The percentage of living patients (41.7%) is almost the same as the percentage of deceased subjects (43.1%; p = 0.002), with high death rates in patients with PA < 4.42°. Phase angle was the most crucial predictor of survival and a risk factor for death in the studied cases.

Adipocytokines and Insulin Resistance: Their Role as Benign Breast Disease and Breast Cancer Risk Factors in a High-Prevalence Overweight-Obesity Group of Women over 40 Years Old.

Insulin levels, adipocytokines, and inflammatory mediators trigger benign breast disease (BBD) and breast cancer (BC). The relationship between serum adipocytokines levels, overweight-obesity, metabolic disturbs, and BC is unclear. Methods: To analyze the serum levels of the adipocytokines, insulin, and the HOMA IR in women without breast disease, with BBD or BC, and the role of these as risk factors for benign breast disease or breast cancer. Results: Adipsin values > 0.91 and visfatin levels > 1.18 ng/mL represent a risk factor to develop BBD in NBD lean women (OR = 18; and OR = 12). Data in overweight-obese women groups confirm the observation due to insulin levels > 2.6 mU/mL and HOMA IR > 0.78, with OR = 60.2 and 18, respectively; adipsin OR = 26.4, visfatin OR = 12. Breast cancer risk showed a similar behavior: Adipsin risk, adjusted by insulin and visfatin OR = 56 or HOMA IR and visfatin OR = 22.7. Conclusion: Adipose tissue is crucial for premalignant and malignant tissue transformation in women with overweight-obesity. The adipocyte−breast epithelium interaction could trigger a malignant transformation in a continuum, starting with BBD as premalignant disease, especially in overweight-obese women.

Quality of Life and Functionality of Head and Neck Cancer Patients Are Diminished As a Function of Sarcopenia and Obesity.

BACKGROUND: Health-related quality of life (QoL) is a measure that allows us to know the patient's perception of well-being and how it is affected by their disease and treatments. In cancer patients, sarcopenia has been associated with low scores on various instruments used to assess the QoL; however, little information is available on the effects of sarcopenia and sarcopenic obesity on the QoL of patients with head and neck cancer (H&NC). METHODS: In this cross-sectional study with 71 H&NC patients aged between 40 and 80 years, we describe the scores on the instruments EORTC QLQ C-30 and EORTC QLQ-H&N35 according to the sarcopenia phenotype (NSG, nonsarcopenic group; SG, sarcopenic group; and SOG, sarcopenic obesity group), hand-grip strength, gait speed, total lymphocyte count, albumin, cholesterol and C-reactive protein, and the relationships between these variables. RESULTS: The prevalence of sarcopenia and sarcopenic obesity was 48% and 28%, respectively. The QoL analysis showed that NSG had higher scores on the physical functioning scale [NSG 93 (83-100); SG 73 (52-88); SOG 83 (53-93), P = .009] and lower scores on the fatigue scale [NSG 11 (0-22); S 39 (30-67); SOG 44 (14-56); P = .004]. The NSG had a higher hand-grip strength (31.1 kg) than SG (24.1 kg, P = .007) and SOG (26.3 kg, P = .001), and a lower C-reactive protein. The SG and SOG showed no differences between them. CONCLUSIONS: Patients with sarcopenia or sarcopenic obesity have lower physical performance and a higher level of fatigue than nonsarcopenic patients. This loss of function can maintain or worsen sarcopenia due to the patient's self-restraint in physical exertion that encourages an increase in muscle tissue.

Morbid obesity is associated with mortality and acute kidney injury in hospitalized patients with COVID-19.

BACKGROUND & AIMS: Mexico has one of the highest mortality rates by COVID-19 worldwide. This may be partially explained by the high prevalence of overweight/obesity found in general population; however, there is limited information in this regard. Furthermore, acute kidney injury (AKI) and need for renal replacement therapy (RRT) associated to obesity in patients with COVID-19 are still topics of discussion. AIM: To explore the association of obesity, particularly morbid obesity, with mortality and kidney outcomes in a Mexican population of hospitalized patients with COVID-19. METHODS: Retrospective cohort study of 773 patients with COVID-19 hospitalized in a tertiary-care teaching hospital in the Mexican state of Jalisco. Baseline body mass index was classified as: normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obesity (30-39.9 kg/m2), and morbid obesity (≥40 kg/m2). AKI was diagnosed according to KDIGO clinical practice guidelines. RESULTS: At baseline, 35% of patients had overweight, 39% obesity and 8% morbid obesity. Patients with obesity were younger, more frequently women and with hypertension than normal weight and overweight patients. Frequency of complications in the univariate analysis were not significantly associated to obesity, however in the multivariate analysis (after adjusting for baseline clinical and biochemical differences), morbid obesity was significantly associated to an increased risk of AKI [OR = 2.70 (1.01-7.26), p = 0.05], RRT [OR = 14.4 (1.46-42), p = 0.02], and mortality [OR = 3.54 (1.46-8.55), p = 0.005]. CONCLUSIONS: Almost half of the sample had obesity and morbid obesity. Morbid obesity was significantly associated to an increased risk of AKI, RRT and mortality in hospitalized patients with COVID-19.

Risk factors for mortality of adult patients with COVID-19 hospitalised in an emerging country: a cohort study.

OBJECTIVE: To describe mortality of in-hospital patients with COVID-19 and compare risk factors between survivors and non-survivors. DESIGN: Prospective cohort of adult inpatients. SETTING: Tertiary healthcare teaching hospital in Guadalajara, Mexico. PARTICIPANTS: All patients with confirmed COVID-19 hospitalised from 25 March to 7 September 2020 were included. End of study: 7 November 2020. PRIMARY OUTCOME MEASURES: Patient survival analysed by the Kaplan-Meier method and comparison of factors by the log-rank test. Mortality risk factors analysed by multivariate Cox's proportional-hazard model. RESULTS: One thousand ten patients included: 386 (38%) died, 618 (61%) alive at discharge and six (0.6%) remained hospitalised. There was predominance of men (63%) and high frequency of overweight-obesity (71%); hypertension (54%); diabetes (40%); and lung (9%), cardiovascular (8%) and kidney diseases (11%); all of them significantly more frequent in non-survivors. Overweight-obesity was not different between groups, but severity of disease (Manchester Triage System and quick Sequential Organ Failure Assessment) was significantly worse in non-survivors, who were also significantly older (65 vs 45 years, respectively) and had haematological, biochemical, coagulation and inflammatory biomarkers more altered than survivors. Mortality predictors were invasive mechanical ventilation (IMV; OR 3.31, p<0.0001), admission to intensive care unit (ICU; OR 2.18, p<0.0001), age (OR 1.02, p<0.0001), Manchester Triage System (urgent OR 1.44, p=0.02; immediate/very urgent OR 2.02, p=0.004), baseline C reactive protein (CRP; OR 1.002, p=0.009) and antecedent of kidney disease (OR 1.58, p=0.04) CONCLUSIONS: Mortality in hospitalised patients with COVID-19 in this emerging country centre seemed to be higher than in developed countries. Patients displayed a high frequency of risk factors for poor outcome, but the need for IMV, ICU admission, older age, more severe disease at admission, antecedent of kidney disease and higher CRP levels significantly predicted mortality.

Body Composition and Biochemical Parameters of Nutritional Status: Correlation with Health-Related Quality of Life in Patients with Colorectal Cancer.

Up to 60% of colorectal cancer (CRC) patients develop malnutrition, affecting treatment effectiveness, increasing toxicity, postoperative complications, hospital stay, and worsening health-related quality of life (HRQOL). This cross-sectional study analyzed data from 48 women and 65 men with CRC. We correlated scores of the scales from the questionnaires EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire Core 30 (QLQ)-C30 and Colorectal Cancer module Colorectal 29 (QLQ-CR29) with patients' body composition and clinical and biochemical indicators of nutritional status. Results: Scores on quality of life were negatively associated with the lymphocyte count (rP = -0.386) and the fat trunk percentage (rP = -0.349) in the women's group. Scores on the physical and role functioning were inversely associated with the adiposity percentage (rP = -0.486 and rP = -0.411, respectively). In men, total skeletal muscle mass (SMM) was positively associated with emotional functioning (rP = 0.450); the trunk SMM was negatively related to fatigue (rP = -0.586), nausea and vomiting (rP = -0.469), pain (rP = -0.506), and financial difficulties (rP = -0.475); additionally, serum albumin was positively related to physical, emotional, and social functioning scales (rPs = 0.395, 0.453, and 0.363, respectively) and negatively to fatigue (rP = -0.362), nausea and vomiting (rP = -0.387), and appetite loss (rP = -0.347). Among the men, the reduced SMM and biochemical, nutritional parameters were related to low scores on the EORTC QLQ-C30 and QLQ-CR29 functioning scales. In conclusion, in patients with CRC, malnourishment could have a profound effect on the patients' functionality and QoL (quality of life).

Posterior extrapelvic tributaries to the internal iliac veins: Morphometrics, types, and variants.

BACKGROUND: In the distribution of the veins, it corresponds in the path and by its affluent to their arterial counterpart. For the pelvic surgeon faced with pelvic surgical pathology, the knowledge of the distribution of the venous vessels is especially important in view of novel surgical techniques and current approaches. The majority of the reports are on common iliac vein (CIV) or the inferior vena cava. To the best of our knowledge, there are no papers describing posterior extrapelvic affluents that drain into the internal iliac vein (IIV). OBJECTIVE: The aim of this work was to describe the pattern of the constitution of the IIV in 17 dissection specimens taken at our institution. MATERIALS AND METHODS: We dissected and registered the anatomic variations of the posterior extrapelvic tributaries to the IIVs. RESULTS: Moreover, we describe the presence of a vein here that is, as far as we know, the first report of a vein that is formed from the posterior extrapelvic veins that drain exactly onto the anterior surface of the CIV. We also describe herein the variants that we have found. CONCLUSIONS: The ignorance of the anatomic variations in the posterior extra-pelvic tributaries to the IIVs (internal iliac veins) can lead to fatal consequences in the patients undergoing pelvic surgery.

ANTECEDENTES: En la descripción de los trayectos venosos, estos corresponden casi exactamente a la distribución de su contraparte arterial, como es el caso de la vena iliaca interna. Para el cirujano que se enfrenta a la patología pélvica, el conocimiento de la distribución de los vasos venosos es de particular importancia. Los reportes que describen los grandes vasos venosos pélvicos se enfocan en las venas iliacas comunes o la vena cava inferior. En nuestro conocimiento, no existen ­reportes que describan los afluentes venosos posteriores que drenan a la vena iliaca interna ni las distancias que separan los vasos entre sí. OBJETIVO: Describir el patrón de constitución de la vena iliaca interna en 17 especímenes cadavéricos disecados en nuestra institución. MATERIAL Y MÉTODOS: Se identificaron los trayectos vasculares de los afluentes venosos posteriores extrapélvicos de las venas iliacas primitivas. RESULTADOS: En específico, describimos la presencia de una variante venosa que, hasta donde hemos revisado, es el primer reporte, pues esta vena posterior extrapélvica drena exactamente en la superficie anterior de la vena iliaca común. También describimos otras variantes encontradas. CONCLUSIONES: Conocer las variantes de los afluentes venosos posteriores extrapélvicos es de vital importancia para el cirujano que realiza cirugía pélvica.

Breast benign disease and breast cancer risk. Overweight-obesity, biochemical, anthropometry. / Enfermedad mamaria benigna y riesgo de cáncer de mama: sobrepeso-obesidad, bioquímica, antropometría.

BACKGROUND: The immunologic, metabolic and anthropometric disturbances of overweight-obesity phenomena are risk factors to breast cancer (BC), particularly in proliferative benign breast disease women (PBBD). OBJECTIVE: To describe the adipocytokine levels, metabolic alteration and anthropometric characteristics in PBBD and its role as risk estimator to BC in a population with high overweight-obesity prevalence. MATERIAL AND METHODS: A cross-sectional study. We realized nutritional diagnosis, anthropometry, and we calculated the waist-height rate (WHR); serum measurement of adipocytokines, insulin and glucose and, HOMA IR determination in 27 PBBD and 27 BC women. We calculated mean, standard deviation, Pearson and Spearman correlation coefficients, Odds Ratio (OR) and confidence intervals through logistic regression as risk estimators of BC; p < 0.05 values were considered significant. RESULTS: Mean age in the PBBD group was minor than BC group, the humeral diameter was greater in BC group women. We did not find differences in anthropometry or adipocytokine levels; in both groups, the predominant somatotype was the endo-mesomorphic. We found higher insulin levels in BC group and a higher percentage of women with WHR > 0.5 too. The WHR > 0.5 + age over 50 were considered risk estimators to develop breast cancer in PBBD women group. CONCLUSION: The WHR >0.5 in women with PBBD over 50 years old could be considered an anthropometric risk estimator to develop BC.

INTRODUCCIÓN: La inflamación, las alteraciones metabólicas y antropométricas del fenómeno sobrepeso-obesidad son factores de riesgo para cáncer de mama (CaM) particularmente en mujeres con enfermedad mamaria benigna proliferativa (EMBP). OBJETIVO: Describir los niveles de adipocitocinas, alteraciones metabólicas y antropométricas en la EMBP y su papel como estimadores de riesgo para CaM en una población con prevalencia de sobrepeso-obesidad de más del 70%. MATERIAL Y MÉTODOS: Estudio transversal analítico en 27 mujeres con CaM y 27 con EMBP. Se realizó diagnóstico nutricional, antropometría y cálculo del índice cintura-talla (ICT); determinación sérica de adipocitocinas, insulina, glucosa y estimación de HOMA IR. Se calcularon promedio y desviaciones estándar, correlaciones de Pearson y Spearman; Odds Ratio (OR) e intervalos de confianza mediante regresión logística como estimadores de riesgo de CaM. Se consideró significativo un valor de p < 0.05. RESULTADOS: La edad del grupo EMBP fue menor. No se observaron diferencias en adipocitocinas ni antropometría (excepto el diámetro humeral fue mayor en CaM). Se observaron mayores niveles de insulina en CaM, y mayor porcentaje de mujeres con ICT > 0.5. El ICT > 0.5 + edad > 50 fueron estimadores de riesgo para CaM. CONCLUSIÓN: Un ICT > 0.5 en mujeres mayores de 50 años podría ser un estimador antropométrico de riesgo de CaM en mujeres con EMBP.

Health-Related Quality of Life and Satisfaction With Health Care: Relation to Clinical Stage in Mexican Patients With Multiple Myeloma.

Multiple myeloma (MM) is characterized by bone pain, pathologic fractures, bone destruction, and secondary hypercalcemia, all these conditions impact on health-related quality of life of patients. The objective was to evaluate the global health state and health-related quality of life in a group of patients with MM who attended a tertiary health-care center of the Instituto Mexicano del Seguro Social in Mexico, through the questionnaires designed by European Organization for Research and Treatment of Cancer (EORTC) quality of life group. Exploratory cross-sectional study in patients with MM treated in a Department of Hematology in a High-Specialty Medical Unit was conducted. Patients older than 18 years of age, men and women, were selected, and their informed written consent was obtained. We included all consecutive cases treated from January 2012 to December 2014. Questionnaires EORTC QLQ-C30, EORTC QLQ-MY20, and EORTC IN-PATSAT-32 were used. We studied 37 patients, 19 (51%) men and 18 women. The mean age was 61.9 years. Twenty-two (59.46%) patients presented with clinical stage III. The mean time for diagnosis was 33.11 months. The most used first-line treatment schedule was melphalan/prednisone/thalidomide (15; 40%). The global health median was 66.67, and symptoms showed a median score of 22.22. Treatment side effects score was 16.67; for general satisfaction, the median score was 75. In conclusion, the patients showed an advanced clinical stage and poor prognosis but had scores higher than 50 in functional scales and lower than 50 for symptom scales. The scores for symptom scales were related to age, renal failure, and disease-free survival. Identification of quality of life and satisfaction of care markers allow for early therapeutic intervention and efficiency and enable a change in quality of life and perception of care in Health Services.

Obesity and adipocytokines in breast cancer and benign breast disease / Obesidad y adipocitocinas en cáncer de mama y enfermedad mamaria benigna

Background: There is a relationship between obesity and the development of breast cancer; adipocytokines are among the mechanisms related. Objective: To describe the impact of obesity in leptin, adiponectin, resistin and tumor necrosis factor-alpha (TNF-alpha) serum levels in women with breast cancer (BC) and benign breast disease (BBD). Methods: A cross-sectional study was carried out with a sample of 54 individuals divided into two groups: BC (n = 27) and BBD (n = 27). Serum levels of leptin, adiponectin, resistin and TNF-alpha were determined. Body mass index (BMI) was calculated. Statistical analysis included mean, standard deviation, median and interquartile range; the differences between groups were determined by Student´s t test, Mann-Whitney U and Kruskall Wallis test to identify differences between the groups. Results: We didn't find any significant differences related to anthropometric characteristics between BC and BBD groups, or to leptin, adiponectin, resistin and TNF-alpha serum levels (p = NS). We found higher leptin serum levels in obese women with BBD compared with non-obese women with BC (med 22.26 versus 4.34 ng/mL; p = 0.028). Adiponectin serum levels in non-obese women from the BC group were higher than serum levels found in non-obese women with BBD (med 7.10 versus 2.22 ng/mL; p = 0.038) Conclusion: We found higher leptin serum levels and lower adiponectin serum levels in BBD women than BC women in this population with high frequency of obesity.

Introducción: existe relación entre la obesidad y el desarrollo de cáncer de mama (CaM); entre los mecanismos implicados están las adipocitocinas. Objetivo: establecer el efecto de la obesidad sobre los valores séricos de leptina, adiponectina, resistina y el factor de necrosis tumoral-alfa (TNF-alfa) en mujeres con CaM y enfermedad mamaria benigna (EMB). Métodos: estudio transversal analítico. Se determinaron los niveles séricos de leptina, adiponectina, resistina y TNF-alfa, así como el índice de masa corporal (IMC) de 27 mujeres con CaM incidente y 27 con EMB. Se utilizaron promedios, desviaciones estándar, medianas (Me) y rangos intercuartílicos, así como las pruebas t de Student, U de Mann-Whitney y Kruskall-Wallis para identificar diferencias entre los grupos. Resultados: no se encontraron diferencias antropométricas, ni en niveles séricos de TNF-alfa, leptina y resistina entre los grupos (p = NS). Los niveles de leptina de las mujeres con EMB y obesidad fueron significativamente superiores que en las mujeres con CaM no obesas (Me 22.26 frente a 4.34 ng/mL; p = 0.028). Los niveles de adiponectina en mujeres con CaM con IMC sin obesidad fueron mayores que los encontrados en pacientes con EMB con IMC y sin obesidad (Me 7.10 frente a 2.22 ng/mL; p = 0.038). Conclusión: en esta población con elevada frecuencia de obesidad, se encontraron niveles mayores de leptina en mujeres con EMB con respecto a las mujeres con CaM; asimismo, se encontró un patrón inverso en adiponectina.

Obesity, Thrombotic Risk, and Inflammation in Cancer.

Neoplasms exhibits a high incidence and mortality rates due to their complex and commonly overlapping clinical, biochemical, and morphologic profiles influenced by acquired or inherited molecular abnormalities, cell of origin, and level of differentiation. Obesity appears related to ~20% of cancers including endometrial, esophageal, colorectal, postmenopausal breast, prostate, and renal. Several factors other than obesity, i.e., insulin, insulin-like growth factor, sexual hormones, and adipokines may play a potential role in neoplasia. Cancer-associated hypercoagulable and thrombotic states are influenced by abnormalities in the vascular wall and susceptibility to invasion, interference in blood flow and increase in circulating tissue factor and thrombin, activation of cell growth factors, the presence of a central catheter, chemotherapies, neoplasm type, and surgery. In cancer, thromboembolic complications are the second most frequent cause of death with pulmonary thromboembolism in ~50% of cases postmortem. Thrombosis worsens prognosis as demonstrated with a survival rate as low as 12% per year vs 36% in nonthrombic patients. Deep vein thrombosis is the most frequent thromboembolic complication in cancer. It is usually detected at diagnosis and within the first 3 months of chemotherapy. The underlining mechanisms of this association should be further studied to identify patients at higher risk and develop adequate prevention, diagnostic, and treatment measures. The D-dimer test can be successfully used to assess the fibrinolytic phase of coagulation and as such is routinely used in suspected cases of deep vein thrombosis and pulmonary thromboembolism. In addition, significant advances have been made in understanding the composition and functional capabilities of the gut microbiota in the inflammatory process, obesity, and its roles in cancer; however, the intricate balance that exists within the microbiota may not only affect the host directly, it can also disrupt the entire microbial community. CONCLUSIONS: Cancer is a prothrombotic and inflammatory state in which the activation of coagulation is related to tumor growth, angiogenesis, and metastasis. It is important to identify the relationship between body mass index with these processes and clarify their importance in cancer prognosis. Future research should answer the question if manipulation of resident microbial communities could potentially improve prognosis and treatment outcome.

[Maternal metabolic diseases related to pre-pregnancy overweight and obesity in mexican women with high risk pregnancy]. / Enfermedades metabólicas maternas asociadas a sobrepeso y obesidad pregestacional en mujeres mexicanas que cursan con embarazo de alto riesgo.

INTRODUCTION: Pre-pregnancy obesity has been proposed as a risk factor related to gestational diabetes and hypertensive disorders during pregnancy. OBJECTIVES: Identify pregnancy related diseases associated with pre-pregnancy obesity as a risk factor ina high risk preganancy patient population. METHODS: 600 patients whose pre-pregnancy obesity had been assessed as a high risk factor were included in the study. The means, standard deviation, median, interquartile intervals, Pearson and Spearman correlation and logistic regression to estimate risk with the odds ratio and 95% confidence intervals were calculated. RESULTS: The mean pre-pregnancy body mass index was 29.59 ± 6.42 kg/m2. The mean for recommended pregnancy weight gain was 2.31 ± 1.03 kg, but the mean of real weight gain was 8.91 ± 6.84 kg. A significant correlation between pre-pregnancy obesity and family history of diabetes mellitus (p=0.000), systemic hypertension (p=0.003), cardiac diseases (p=0.000), dyslipidemia (p=0.000) and obesity (p=0.000) was identified. Pre-pregnancy obesity was identified as a risk factor for the development of gestational diabetes (OR: 1.95; IC95%: 1.39 to 2.76; p=0.000) in this kind of patient. DISCUSSION AND CONCLUSION: 75% of high risk pregnancy women in a high specialty hospital in West Mexico are overweight or obese when they become pregnant. These are risk factors in the development of gestational diabetes.

Descriptive, Longitudinal Study Results Applied to Statistical Models to Assess the Impact of Early Microbiological Cultures on the Economic Burden of Treatment for Infected Diabetic Foot Ulcers at a Mexican Public Health Facility.

Infection plays a critical role in health care and impacts the cost of the treatment of diabetic foot ulcers (DFU). To examine the cost reduction associated with the multidisciplinary treatment of infected DFU (IDFU) by obtaining early (ie, within 48 hours of admission) microbiological culture results, a descriptive, longitudinal study was conducted. Data were collected prospectively from patient medical charts of a cohort of 67 patients (mean age, 56.14 ± 12.3 years; mean duration of diabetes, 14.95 ± 8 years) with IDFU treated at a Mexican public health facility from January 1 to April 30, 2010. Information included demographic data (age, gender, marital status, time elapsed since first diagnosis of diabetes mellitus type 2 [DM2]), and the following clinical records: Wagner classification, bacterium type, antimicrobial resistance, length of hospital stay, and the antibiotic schedule utilized, as well as number and type of laboratory tests, medications, intravenous therapy, surgical and supportive treatment, type and number of specialists, and clinical outcome. Microcosting was used to calculate the unit cost of each medical treatment element. Using the Monte Carlo and Markov predictive simulation economical models, cost reduction associated with early identification of the specific microorganism through bacterial culture in IDFU was estimated. Based on the statistical results, differences between real and estimated costs when including early microbiological culture were identified and the number and type of most common species of infectious bacteria were detected. The total cost observed in the patient cohort was $502 438.04 USD, mean cost per patient was $7177.69 ± $5043.51 USD, and 72.75% of the total cost was associated with the hospital stay length. The cost of the entire treatment including antibiotics was $359 196.16 USD; based on the simulation of early microbiological culture, the model results showed cost could be reduced by 10% to 25% (in this study, the cost could be as low as $304 624.63 USD). The use of early microbiological cultures on IDFU to determine the appropriate antibiotic can reduce treatment costs by >30% if hospital stay is part of the consideration.

Human papillomavirus genotyping by Linear Array and Next-Generation Sequencing in cervical samples from Western Mexico.

BACKGROUND: The Linear Array® (LA) genotyping test is one of the most used methodologies for Human papillomavirus (HPV) genotyping, in that it is able to detect 37 HPV genotypes and co-infections in the same sample. However, the assay is limited to a restricted number of HPV, and sequence variations in the detection region of the HPV probes could give false negatives results. Recently, 454 Next-Generation sequencing (NGS) technology has been efficiently used also for HPV genotyping; this methodology is based on massive sequencing of HPV fragments and is expected to be highly specific and sensitive. In this work, we studied HPV prevalence in cervixes of women in Western Mexico by LA and confirmed the genotypes found by NGS. METHODS: Two hundred thirty three cervical samples from women Without cervical lesions (WCL, n = 48), with Cervical intraepithelial neoplasia grade 1 (CIN I, n = 98), or with Cervical cancer (CC, n = 87) were recruited, DNA was extracted, and HPV positivity was determined by PCR amplification using PGMY09/11 primers. All HPV- positive samples were genotyped individually by LA. Additionally, pools of amplicons from the PGMY-PCR products were sequenced using 454 NGS technology. Results obtained by NGS were compared with those of LA for each group of samples. RESULTS: We identified 35 HPV genotypes, among which 30 were identified by both technologies; in addition, the HPV genotypes 32, 44, 74, 102 and 114 were detected by NGS. These latter genotypes, to our knowledge, have not been previously reported in Mexican population. Furthermore, we found that LA did not detect, in some diagnosis groups, certain HPV genotypes included in the test, such as 6, 11, 16, 26, 35, 51, 58, 68, 73, and 89, which indicates possible variations at the species level. CONCLUSIONS: There are HPV genotypes in Mexican population that cannot be detected by LA, which is, at present, the most complete commercial genotyping test. More studies are necessary to determine the impact of HPV-44, 74, 102 and 114 on the risk of developing CC. A greater number of samples must be analyzed by NGS for the most accurate determination of Mexican HPV variants.

Porcentaje de adiposidad y su relación con el índice de inmunorreactividad de los receptores hormonales en mujeres mexicanas con cáncer de mama / Adiposity percentage relationship with hormone receptors immunoreactive score in breast cancer Mexican women

INTRODUCTION: Adipose tissue is an important estrogen resource and they are involved in breast cancer development. OBJECTIVE: To establish the relationship between adiposity percentage and the estrogen and progesterone receptors immunoreactive score in Mexican women with breast cancer. METHODS: This is a transversal and analytical study. We identified breast cancer women with cancer histologic diagnosis. We calculated: adiposity percentage and immunoreactive score. We performed correlation analysis between adiposity percentage, body mass index, diabetes mellitus and arterial hypertension, with estrogen and progesterone receptors in breast cancer samples. We perform logistic regression and Odds Ratio estimations. RESULTS: We studied 43 patients with breast cancer and we observed association between adiposity percentage and estrogen and progesterone immnunoreactive score (rP 0.470; p 0.003 and rP 0.328; p 0.042, respectively). The most important risk factor in breast cancer positive to estrogen receptors was obesity (OR 19.1, IC95% 2.1 a 169.1, p 0.008), and previous obesity in breast cancer positive to progesterone receptors (OR 20.7, IC95% 2.3 a 185.9, p 0.007). DISCUSSION: Adiposity percentage is an important risk factor to develop breast cancer positive to hormone receptors related with the risk of breast cancer positive to hormonal receptors (AU)

Introducción: El tejido adiposo es una importante fuente de estrógenos, los cuales se encuentran implicados en el desarrollo de cáncer de mama. Objetivo: Establecer la relación entre el porcentaje de adiposidad y el índice de inmunorreactividad de los receptores a estrógenos y a progesterona en mujeres mexicanas con cáncer de mama. Métodos: Estudio transversal analítico en pacientes con cáncer de mama confirmado con estudio histopatológico. Se estimó el % de adiposidad, y el índice de inmunorreactividad. Se realizó el análisis de correlación entre el porcentaje de adiposidad, el IMC, la presencia de DM2 e hipertensión arterial con la expresión de receptores a estrógeno y progesterona y regresión logística con cálculo de Odds Ratio. Resultados: Se estudiaron 43 pacientes con cáncer de mama y se observó asociación entre el porcentaje de adiposidad y el índice de inmunoreactividad para los RE y RP (rP 0,470; p 0,003 y rP 0,328; p 0,042 respectivamente). El factor de riesgo más importante en cáncer positivo a receptores estrogénicos fue la obesidad (OR 19,1, IC 95% 2,1 a 169,1, p 0,008) y obesidad previa en cáncer positivo a receptores a progesterona (OR 20,7, IC 95% 2,3 a 185,9, p 0,007). Conclusión: El porcentaje de adiposidad es un factor de riesgo importante para desarrollar cáncer de mama positivo a receptores hormonales (AU)