Expression of Programmed Death Ligand 1 in Breast Cancer in Mexican Women.

Background: Breast cancer is one of the most common malignant forms of neoplasia worldwide; programmed death protein 1 (PD-1), an inhibitory receptor of T lymphocytes, and its ligand programmed death ligand 1 (PD-L1), play an important role in the ability of tumor cells to evade the host's immune system. Methods: We conducted a descriptive, observational study using retrospective data and an open evaluation using immunohistochemistry to determine the general prevalence of PD-L1 expression in 63 women with breast cancer who underwent a modified radical mastectomy, or quadrantectomy, with axillary lymph node removal. Results: The prevalence of PD-L1 expression was 32% in patients with breast cancer treated with radical mastectomy. PD-L1 expression was higher in patients with large tumor size (19% for pT1, 37% for pT2, 50% for pT3, and 100% for pT4), metastasis in regional lymph nodes (25% for N0, 38% for N1, 75% for pN2, and 38% for pN3), and higher histological grade carcinoma (0% for grade 1, 23% for grade 2, and 50% for grade 3). Conclusions: These findings suggest that PD-L1 expression is heterogeneous in breast cancer tumors and that its expression varies highly in tumor regions over time. The evaluation of PD-L1 expression is significant, because of the therapeutical implications that could improve the outcomes and prognosis of these patients.

Impact of the Discordance Between Scales of Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium in Patients' Prognosis With Metastatic Renal Cancer.

Background: In Mexico, about 30% of renal cancer patients are diagnosed in a metastatic state. Despite the recent advances in the treatment of cancer, metastatic renal cancer is still an incurable illness. Thus, identifying prognostic factors helps improve prognosis accuracy and survival prediction for patients. Methods: In this study, we retrospectively analyzed 26 patients with histological diagnosis of renal cell carcinoma, including clear cell and other subtypes in stage IV (metastatic), recurrent or unresectable disease. We performed a multivariate analysis of overall survival regarding the congruity between prognostic scales. Results: Our results showed a significant difference in favor of patients with congruity between scales for progression-free survival (18.9 vs. 3.1 months; P = 0.048) and a tendency towards better overall survival in patients with the congruity of both scales compared to the discordant patients (112 vs. 32 months; P = 0.99). Conclusion: This study highlights the discordance between Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium scales, which was associated with worse prognosis with a significant difference in progression-free survival but not in overall survival.

Fibroblast growth factor 21 is associated with increased serum total antioxidant capacity and oxidized lipoproteins in humans with different stages of chronic kidney disease.

Background and aims: Oxidative stress (OS) induces the production of fibroblast growth factor 21 (FGF21). Previous data have revealed that FGF21 protects cells from OS injury and death, making it a potential therapeutic option for many diseases with increased OS. However, the association of this growth factor with OS markers in humans with chronic kidney disease (CKD) remains unknown. This study aims to evaluate the association of serum FGF21 with serum total antioxidant capacity (TAC) and oxidized low-density lipoproteins (OxLDL) in subjects in different stages of kidney disease. Methods: This is a cross-sectional study that included 382 subjects with different stages of CKD, irrespective of type 2 diabetes (T2D) diagnosis. Associations of serum FGF21 with OxLDL, TAC, sex, age, body mass index (BMI), fasting plasma glucose, estimated glomerular filtration rate (eGFR), T2D, and smoking, were evaluated through bivariate and partial correlation analyses. Independent associations of these variables with serum FGF21 were evaluated using multiple linear regression analysis. Results: Serum FGF21 was significantly and positively correlated with age (r = 0.236), TAC (lnTAC) (r = 0.217), and negatively correlated with eGFR (r = -0.429) and male sex (r = -0.102). After controlling by age, sex, BMI, T2D, smoking, and eGFR; both TAC and OxLDL were positively correlated with FGF21 (r = 0.117 and 0.158 respectively, p < 0.05). Using multiple linear regression analysis, eGFR, male sex, T2D, OxLDL, and TAC were independently associated with serum FGF21 (STDß = -0.475, 0.162, -0.153, 0.142 and 0.136 respectively; p < 0.05 for all) adjusted for age, BMI, smoking, and fasting plasma glucose. Conclusion: A positive association between serum FGF21 and OS has been found independently of renal function in humans. Results from the present study provide novel information for deeper understanding of the role of FGF21 in OS in humans with CKD and T2D; mechanistic studies to explain the association of serum FGF21 with oxidative stress in CKD are needed.

Diabetes, Active Disease, and Afternoon Serum Cortisol Levels Predict Cushing's Disease Mortality: A Cohort Study.

CONTEXT: Cushing's disease (CD) is a life-threating disease, with increased mortality in comparison with the general population. OBJECTIVE: This study aimed to evaluate standardized mortality ratios (SMRs) in CD patients. We also analyzed independent risk factors related to increased mortality. DESIGN: We conducted a longitudinal cohort study in a 3rd level specialty center, from 1979 to 2018, in patients with CD. RESULTS: From 1375 cases with a pathology diagnosis of pituitary adenoma, 191 cases had the confirmed diagnosis of CD (14%). A total of 172 patients completed follow-up, with a mean age at diagnosis of 33 ±â€…11 years, female predominance (n = 154, 89.5%), majority of them with microadenoma (n = 136, 79%), and a median follow-up of 7.5 years (2.4-15). Eighteen patients (10.5%) died, 8 of them (44%) were with active CD, 8 (44%) were under remission, and 2 (11%) were under disease control. Estimated all-cause SMR = 3.1, 95% confidence interval (CI) 1.9-4.8, P < 0.001. Cardiovascular disease was the main cause of death (SMR = 4.2, 1.5-9.3, P = 0.01). Multivariate Cox regression models adjusted for potential cofounders showed that diabetes (HR = 5.2, IC 95% 1.8-15.4, P = 0.002), high cortisol levels after 1600 hours at diagnosis (3.4, 2.3-7.0, P = 0.02), and active CD (7.5, 3.8-17.3, P = 0.003) significantly increased the risk of mortality. CONCLUSIONS: Main cause of CD mortality was cardiovascular disease. Main risk factors for mortality were uncontrolled diabetes, persistently high cortisol levels after 1600 hours at diagnosis, and active disease at last follow-up.

Bone mineral density and low bone mass in severely burned patients: A retrospective cohort study.

INTRODUCTION: Severe burns can alter bone metabolism through different mechanisms. Despite prior published studies describing the association between burns and a decrease in bone mineral density (BMD), no clinical guidelines currently exist recommending the systematic evaluation of bone health in patients after severe burns. This study aims to describe the BMD of individuals with severe burn injuries and healthy controls and determine the frequency of low-to-normal bone mass (LNBM) and BMD below the expected range for age (BEA). MATERIALS AND METHODS: We conducted a retrospective cohort of patients with either severe thermal or electrical burns and healthy controls paired by gender and age. We performed a dual-energy X-ray absorptiometry at least 90 days after the burn and collected data from each patient's clinical evaluation and clinical file. RESULTS: A total of 77 patients (64 men and 13 women) and their paired controls were included in the study (age [mean ± standard deviation, SD]: 30.37 ± 8.66 years). Patients participated in the study an average of 315 ± 438 days after their burn. The BMD (grs/cm2) in total hip burned vs controls was: 0.998 ± 0.135 vs 1.059 ± 0.12 (p = 0.004); femoral neck 0.876 ± 0.121 vs 0.915 ± 0.097 (p = 0.031), spine 0.977 ± 0.127 vs 1.003 ± 0.076 (p = 0.132).The Z-scores for total hip were - 0.06 ± 1.05 vs 0.41 ± 0.80 (p = 0.002); for neck -0.39 ± 0.89 vs -0.01 ± 0.77 (p = 0.005); and for spine -0.75 ± 1.11 vs -0.32 ± 0.73 (p = 0.005). The proportion of subjects with BMD BEA in burns vs controls was 5.2 vs 1.2% (p = 0.05) in total hip, 3.9 vs 0% (p = 0.045) in the neck, and 18.2 vs 1.2% (p = 0.001) in the spine. The logistic regression model found-in burn patients vs controls-an OR of 9.83 for BMD BEA (CI 95%: 2.17-44.45, p = 003), OR = 4.05 for electrical burns (CI 95%: 1.72-20.89, p = 004) and OR = 15.16 for thermal burns (CI 95%: 2.91-79.00, p = 001). The model also found an OR = 2.48 for LNBM (CI 95%: 1.25-4.93, p = 0.009). The burn variables associated with BMD BEA at any site in the patients were BMI >25 Kg/m2 with an OR = 0.180 (CI 95%: 0.046-0.710, p = 0.014); and the lower limb amputation with an OR = 7.33 (CI 95%; 1.12-48.33, p = 0.038). Five burn patients had a fragility fracture. CONCLUSION: BMD was significantly lower in severely burned patients than in controls, and the proportion BMD BEA cases was significantly higher in the burn patient sample. Severe burns are a strong independent predictor of bone loss, and this risk is maintained for an extended period after the burn.

Predictive Factors for Returning to Work in Burn Adult Patients That Were Working Before Their Injury.

The goal of this study was to identify predictive factors that influence return to work in burn patients treated at the National Center for Burn Care and Research at the National Institute of Rehabilitation (CENIAQ) in México City. This is a retrospective case-control study that included all burn patients of working age (16-91 years old), treated between January 2011 and December 2013. Patients were divided into two groups: unemployed (no work group) and those who returned to work (RTW). The statistical analysis was performed by a logistic regression univariate and multivariate analysis. A total of 210 subjects were included in the study. The mean age was 38 ± 15 years and 66.7% of them were male. One hundred sixty-five patients (79.6%) were able to return to work after treatment. Through univariate analysis it was found that the predictive factors for not returning to work after injury were: education lower than elementary school (OR: 3.59; CI 95%: 1.79-7.32); history of epilepsy prior to burn injury (OR: 10.18; CI 95%: 1.9-54.43); total burned surface area (TBSA) ≥20% (OR: 2.87; CI 95%: 1.46-5.64); third-degree burns (OR: 2.64; CI 95%: 1.32-5.29); hospital stay ≥20 days (OR: 2.8; CI 95%: 1.47-5.68); length of stay in the burn intensive care unit (OR: 2.5; CI 95%: 1.25-4.97); secondary infection (OR: 2.24; CI 95%: 1.15-4.38); amputations (one or more regardless of amputation level; OR: 8; CI 95%: 2.52-25.30); burn of the upper extremity (shoulder; OR: 2.21; CI 95%: 0.97-5.03); thigh (OR: 2.41; CI 95%: 1.32-5.14); and knee (OR: 2.81; CI 95%: 1.21-6.55). Some of these factors have never been reported by other authors.

Fibroblast growth factor 21 and its novel association with oxidative stress.

Fibroblast growth factor 21 (FGF21) is an endocrine-member of the FGF family. It is synthesized mainly in the liver, but it is also expressed in adipose tissue, skeletal muscle, and many other organs. It has a key role in glucose and lipid metabolism, as well as in energy balance. FGF21 concentration in plasma is increased in patients with obesity, insulin resistance, and metabolic syndrome. Recent findings suggest that such increment protects tissue from an increased oxidative stress environment. Different types of physical stress, such as strenuous exercising, lactation, diabetic nephropathy, cardiovascular disease, and critical illnesses, also increase FGF21 circulating concentration. FGF21 is now considered a stress-responsive hormone in humans. The discovery of an essential response element in the FGF21 gene, for the activating transcription factor 4 (ATF4), involved in the regulation of oxidative stress, and its relation with genes such as NRF2, TBP-2, UCP3, SOD2, ERK, and p38, places FGF21 as a key regulator of the oxidative stress cell response. Its role in chronic diseases and its involvement in the treatment and follow-up of these diseases has been recently the target of new studies. The diminished oxidative stress through FGF21 pathways observed with anti-diabetic therapy is another clue of the new insights of this hormone.