CD68 and CD83 immune populations in non-metastatic axillary lymph nodes are of prognostic value for the survival and relapse of breast cancer patients.

BACKGROUND: The foremost cause of death of breast cancer (BC) patients is metastasis, and the first site to which BC predominantly metastasizes is the axillary lymph node (ALN). Thus, ALN status is a key prognostic indicator at diagnosis. The immune system has an essential role in cancer progression and dissemination, so its evaluation in ALNs could have significant applications. In the present study we aimed to investigate the association of clinical-pathological and immune variables in the primary tumour and non-metastatic ALNs (ALNs-) of a cohort of luminal A and triple-negative BC (TNBC) patients with cancer-specific survival (CSS) and time to progression (TTP). METHODS: We analysed the differences in the variables between patients with different outcomes, created univariate and multivariate Cox regression models, validated them by bootstrapping and multiple imputation of missing data techniques, and used Kaplan-Meier survival curves for a 10-years follow-up. RESULTS: We found some clinical-pathological variables at diagnosis (tumour diameter, TNBC molecular profile and presence of ALN metastasis), and the levels of several immune markers in the two studied sites, to be associated with worse CSS and TTP. Nevertheless, only CD68 and CD83 in ALNs- were confirmed as independent prognostic factors for TTP. CONCLUSIONS: The study identified the importance of macrophage and dendritic cell markers as prognostic factors of relapse for BC. We highlight the importance of studying the immune response in ALNs-, which could be relevant to the prediction of BC patients' outcome.

Differences in the Immune Response of the Nonmetastatic Axillary Lymph Nodes between Triple-Negative and Luminal A Breast Cancer Surrogate Subtypes.

Breast cancer (BC) comprises four immunohistochemical surrogate subtypes of which triple-negative breast cancer (TNBC) has the highest risk of mortality. Axillary lymph nodes (ALNs) are the regions where BC cells first establish before distant metastasis, and the presence of tumor cells in the ALN causes an immune tolerance profile that contrasts with that of the nonmetastatic ALN (ALN-). However, few studies have compared the immune components of the ALNs- in BC subtypes. The present study aimed to determine whether differences between immune populations in the primary tumor and ALNs- were associated with the luminal A or TNBC subtype. We evaluated a retrospective cohort of 144 patients using paraffin-embedded biopsies. The TNBC samples tended to have a higher histologic grade and proliferation index and had higher levels of immune markers compared with luminal A in primary tumors and ALNs-. Two methods for validating the multivariate analysis found that histologic grade, intratumoral S100 dendritic cells, and CD8 T lymphocytes and CD57 natural killer cells in the ALNs- were factors associated with TNBC, whereas CD83 dendritic cells in the ALNs- were associated with the luminal A subtype. In conclusion, we found that intratumoral regions and ALNs- of TNBC contained higher concentrations of markers related to immune tolerance than luminal A. This finding partially explains the worse prognosis of patients with TNBC.

Worsening renal function during an episode of acute heart failure and its relation to short- and long-term mortality: associated factors in the Epidemiology of Acute Heart Failure in Emergency Departments- Worsening Renal Function study. / Factores asociados con el empeoramiento de la función renal durante un episodio de insuficiencia cardiaca aguda y su relación con la mortalidad a corto y largo plazo: estudio EAHFE - EFRICA.

OBJECTIVES: To identify factors associated with worsening renal function (WRF) and explore associations with higher mortality in patients with acute heart failure (AHF). MATERIAL AND METHODS: Seven emergency departments (EDs) in the EAHFE-EFRICA study (Spanish acronym for Epidemiology of AHF in EDs - WRF in AHF) consecutively included patients with AHF and creatinine levels determined in the ED and between 24 and 48 hours later. Patients with WRF were identified by an increase in creatinine level of 0.3 mg/dL or more. Forty-seven clinical characteristics were explored to identify those associated with WRF. To analyze for 30-day all-cause mortality we calculated odds ratios (ORs). To analyze mortality at the end of follow-up and by trimester, adjusted for between-group differences, we calculated hazard ratios (HRs). The data were analyzed by subgroups according to age, sex, baseline creatinine levels, AHF type, and risk group. RESULTS: A total of 1627 patients were included. The subgroup of 220 (13.5%) with WRF were older, had higher systolic blood pressure, were more often treated with morphine, and had chronic renal failure; there was also a higher rate of hypertensive crisis as the trigger for AHF in patients with WRF. However, only chronic renal failure was independently associated with WRF (adjusted OR, 1.695; 95% CI, 1.264-2.273). The rate of 30-day mortality was 13.1% overall but higher in patients with WRF (20.9% vs 11.8% in patients without WRF; adjusted OR, 1.793; 95% CI, 1.207-2.664). Accumulated mortality at 18 months (average follow-up time, 14 mo/patient) was 40.0% overall but higher in patients with WRF (adjusted HR, 1.275; 95% CI, 1.018-1.598). Increased risk was greater in the first trimester. Subgroup analyses revealed no differences. CONCLUSION: AHF with WRF in the first 48 hours after ED care is associated with higher mortality, especially in the first trimester after the emergency.

OBJETIVO: Identificar los factores asociados con el empeoramiento de la función renal (EFR) y si este se asocia a mayor mortalidad en pacientes que presentan un episodio de insuficiencia cardiaca aguda (ICA). METODO: Participaron 7 servicios de urgencias (SU) que incluyeron consecutivamente pacientes con ICA con determinación de creatinina en urgencias y a las 24-48 horas, y se identificaron aquellos con EFR (incremento de creatinina $ 0,3 mg/dL). Entre 47 características clínicas, se identificó las asociadas a EFR. Se investigó la mortalidad por cualquier causa a 30 días (OR) y al final del seguimiento (HR), esta última global y por periodos trimestrales, que se ajustó por las diferencias entre grupos. Se analizaron subgrupos según edad, sexo, creatinina basal, tipo de ICA y grupo de riesgo. RESULTADOS: Se incluyeron 1.627 pacientes, 220 (13,5%) con EFR, los cuales presentaban mayor edad, presión arterial sistólica, crisis hipertensiva como precipitante, tratamiento con morfina e insuficiencia renal crónica, aunque solo esta última se asoció independientemente a EFR (ORajustada = 1,695, IC 95% = 1,264-2,273). La mortalidad a 30 días fue de 13,1% (mayor en pacientes con EFR: 20,9% vs 11,8%, ORajustada = 1,793, IC 95% = 1,207-2,664) y la mortalidad acumulada a 18 meses (tiempo medio de seguimiento 14 meses/paciente) fue del 40,0% (mayor en pacientes con EFR: HRajustada = 1,275, IC 95% = 1,018-1,598). Este incremento de riesgo fue durante el primer trimestre. El análisis de subgrupos no mostró diferencias. CONCLUSIONES: La ICA con EFR en las primeras 48 horas posteriores a la atención en el SU se asocia a mayor mortalidad, que se concentra durante el primer trimestre.

Factores asociados con el empeoramiento de la función renal durante un episodio de insuficiencia cardiaca aguda y su relación con la mortalidad a corto y largo plazo: estudio EAHFE - EFRICA / Worsening renal function during an episode of acute heart failure and its relation to short- and long-term mortality: associated factors in the Epidemiology of Acute Heart Failure in Emergency Departments- Worsening Renal Function study

OBJETIVO: Identificar los factores asociados con el empeoramiento de la función renal (EFR) y si este se asocia a mayor mortalidad en pacientes que presentan un episodio de insuficiencia cardiaca aguda (ICA). MÉTODO: Participaron 7 servicios de urgencias (SU) que incluyeron consecutivamente pacientes con ICA con determinación de creatinina en urgencias y a las 24-48 horas, y se identificaron aquellos con EFR (incremento de creatinina $ 0,3 mg/dL). Entre 47 características clínicas, se identificó las asociadas a EFR. Se investigó la mortalidad por cualquier causa a 30 días (OR) y al final del seguimiento (HR), esta última global y por periodos trimestrales, que se ajustó por las diferencias entre grupos. Se analizaron subgrupos según edad, sexo, creatinina basal, tipo de ICA y grupo de riesgo. RESULTADOS: Se incluyeron 1.627 pacientes, 220 (13,5%) con EFR, los cuales presentaban mayor edad, presión arterial sistólica, crisis hipertensiva como precipitante, tratamiento con morfina e insuficiencia renal crónica, aunque solo esta última se asoció independientemente a EFR (ORajustada = 1,695, IC 95% = 1,264-2,273). La mortalidad a 30 días fue de 13,1% (mayor en pacientes con EFR: 20,9% vs 11,8%, ORajustada = 1,793, IC 95% = 1,207-2,664) y la mortalidad acumulada a 18 meses (tiempo medio de seguimiento 14 meses/paciente) fue del 40,0% (mayor en pacientes con EFR: HRajustada = 1,275, IC 95% = 1,018-1,598). Este incremento de riesgo fue durante el primer trimestre. El análisis de subgrupos no mostró diferencias. CONCLUSIÓN: La ICA con EFR en las primeras 48 horas posteriores a la atención en el SU se asocia a mayor mortalidad, que se concentra durante el primer trimestre

OBJECTIVE: To identify factors associated with worsening renal function (WRF) and explore associations with higher mortality in patients with acute heart failure (AHF). METHODS: Seven emergency departments (EDs) in the EAHFE-EFRICA study (Spanish acronym for Epidemiology of AHF in EDs - WRF in AHF) consecutively included patients with AHF and creatinine levels determined in the ED and between 24 and 48 hours later. Patients with WRF were identified by an increase in creatinine level of 0.3 mg/dL or more. Forty-seven clinical characteristics were explored to identify those associated with WRF. To analyze for 30-day all-cause mortality we calculated odds ratios (ORs). To analyze mortality at the end of follow-up and by trimester, adjusted for between-group differences, we calculated hazard ratios (HRs). The data were analyzed by subgroups according to age, sex, baseline creatinine levels, AHF type, and risk group. RESULTS: A total of 1627 patients were included. The subgroup of 220 (13.5%) with WRF were older, had higher systolic blood pressure, were more often treated with morphine, and had chronic renal failure; there was also a higher rate of hypertensive crisis as the trigger for AHF in patients with WRF. However, only chronic renal failure was independently associated with WRF (adjusted OR, 1.695; 95% CI, 1.264-2.273). The rate of 30-day mortality was 13.1% overall but higher in patients with WRF (20.9% vs 11.8% in patients without WRF; adjusted OR, 1.793; 95% CI, 1.207-2.664). Accumulated mortality at 18 months (average follow-up time, 14 mo/patient) was 40.0% overall but higher in patients with WRF (adjusted HR, 1.275; 95% CI, 1.018-1.598). Increased risk was greater in the first trimester. Subgroup analyses revealed no differences. CONCLUSION: AHF with WRF in the first 48 hours after ED care is associated with higher mortality, especially in the first trimester after the emergency

Immune response profile of primary tumour, sentinel and non-sentinel axillary lymph nodes related to metastasis in breast cancer: an immunohistochemical point of view.

Approximately 1.67 million new cases of breast cancer (BC) are diagnosed annually, and patient survival significantly decreases when the disease metastasizes. The axillary lymph nodes (ALNs) are the main doorway for BC tumoral cell escape, through which cells can disseminate to distant organs. The immune response, which principally develops in the lymph nodes, is linked to cancer progression, and its efficacy at controlling tumoral growth is compromised during the disease. Immunohistochemistry (IHC) is one of the most widely used research techniques for studying the immune response. It allows the measurement of the expression of particular markers related to the immune populations. This review focuses on the role of the immune populations in the primary tumour in the locoregional metastasis of the ALN, and the relationship of the immune response in these regions to distant metastasis. We considered only studies of immune cells using IHC techniques. In particular, lymphocytes, macrophages and dendritic cells all play important roles in BC and have been extensively studied. Although further research is needed, there is much evidence of their role in the invasion of the ALN and distant organs. Their association with tumoral growth or protection has not yet been demonstrated decisively and is very likely to be determined by a combination of factors. Moreover, even though IHC is a widely used technique in cancer diagnosis and research, there is still room for improvement, since its quantification needs to be properly standardized.

Psychiatric factors affecting recovery after a long term treatment program for substance use disorder.

Psychiatric comorbidity can negatively impact the course of addictions. Psychiatric features of patients who continued treatment after the first stage of an addiction program have not been sufficiently analysed. Therefore, only these patients were included in order to compare psychiatric comorbidity and clinical factors between patients who were able or not to complete a long term substance-free program. Treatment-completion status of 245 patients was systematically recorded. Addiction severity, psychiatry comorbidity, and psychological symptoms were evaluated. No significant differences were found regarding comorbid psychiatric diagnoses and the completion of the treatment. Longer treatment duration (OR: 1.22; p < 0.01), higher educational level (OR: 2.37; p = 0.02), and cocaine dependence as main substance (OR: 3.68; p < 0.01) were found to be related to increased likelihood in completing the treatment. Patients with higher severity of alcohol consumption (OR: 0.06; p = 0.02) and more depressive symptoms (OR: 0.95; p = 0.01) completed the treatment less frequently. Moreover, differences regarding employment problems, treatment facilities, anxiety symptoms, dysfunctional impulsivity, and mental HRQoL were found. It is concluded that comorbid psychiatric diagnoses do not determine treatment outcomes. However, therapeutic and psychological factors have a major influence on the likelihood to complete a long-term treatment program.

History of sexual, emotional or physical abuse and psychiatric comorbidity in substance-dependent patients.

Sexual, emotional or physical abuse history is a risk factor for mental disorders in addicted patients. However, the relationship between addiction and abuse lifespan is not well known. This study aims to compare clinical and psychopathological features of addicted patients according to the experience of abuse and to the number of different types of abuse suffered. Bivariate and multivariate analyses were conducted. 512 addicted patients seeking treatment were included, 45.9% reported abuse throughout life (38.9% emotional, 22.3% physical and 13.5% sexual abuse). It was found that female gender; depressive symptoms and borderline personality disorder were independently associated with history of any abuse throughout life. As well, it was found that 14% have been suffered from all three types of abuse (sexual, emotional and physical), 34.5% from two and 55.5% from one type. Female gender and borderline personality disorder were independently associated independently with a greater number of different types of abuse. Results suggest that history of abuse is frequent among substance-dependent patients and these experiences are more prevalent in women and are associated with more psychiatric comorbidity.