Hematological Alterations after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have benefits for survival in some cancers with peritoneal metastasis. Hematologic toxicity described rate is 2 to 38%. METHODS: Patients admitted to an intensive care unit (ICU) after CRS and HIPEC over 78 months. The data recorded were demographic characteristics, the severity of illness, complete blood samples, the type of cancer and extension, HIPEC drug and temperature, ICU and hospital stay and mortality, bleeding, and the need for transfusion of blood products. RESULTS: Of the 96 patients included, 77.1% presented hematological complications: 8.3% leukopenia (<4000/mm3 leucocytes), 66.7% anemia (hemoglobin < 10 mg/dL), and 22.9% coagulopathy (INR < 1.5, or/and aPTT < 45 s, or/and platelet count < 100,000/mm3, or/and <100 mg/dL of serum fibrinogen). Leukopenia was higher in ovarian cancer or those treated with doxorubicin. Females with anemia, ovarian cancer, and those treated with cisplatin or doxorubicin had longer ICU stays. Bleeding complications were low-corrected in a conservative manner. The median ICU stay was 5 (4.0-5.0) days. The ICU mortality rate was 1.0%. CONCLUSIONS: In our study, 77.1% of patients treated with CRS and HIPEC developed hematological complications during the postoperative period; the majority of them were not severe and resolved spontaneously, without an effect on mortality or hospital stay.

Nutrition, Epigenetics, and Major Depressive Disorder: Understanding the Connection.

Major depressive disorder (MDD) is a complex, multifactorial disorder of rising prevalence and incidence worldwide. Nearly, 280 million of people suffer from this leading cause of disability in the world. Moreover, patients with this condition are frequently co-affected by essential nutrient deficiency. The typical scene with stress and hustle in developed countries tends to be accompanied by eating disorders implying overnutrition from high-carbohydrates and high-fat diets with low micronutrients intake. In fact, currently, coronavirus disease 2019 (COVID-19) pandemic has drawn more attention to this underdiagnosed condition, besides the importance of the nutritional status in shaping immunomodulation, in which minerals, vitamins, or omega 3 polyunsaturated fatty acids (ω-3 PUFA) play an important role. The awareness of nutritional assessment is greater and greater in the patients with depression since antidepressant treatments have such a significant probability of failing. As diet is considered a crucial environmental factor, underlying epigenetic mechanisms that experience an adaptation or consequence on their signaling and expression mechanisms are reviewed. In this study, we included metabolic changes derived from an impairment in cellular processes due to lacking some essential nutrients in diet and therefore in the organism. Finally, aspects related to nutritional interventions and recommendations are also addressed.

[HLA DRB1*, DQB1*, DPA1*, and DPB1* and their association with the pathogenesis of leukemia in the population of Venezuela]. / HLA DRB1*, DQB1*, DPA1* y DPB1* y su asociación con la patogénesis de las leucemias en población venezolana.

BACKGROUND: The HLA complex involved is a factor in the pathogenesis of leukemia. OBJECTIVES: The presence of class II HLA alleles DRB1 *, DQB1 *, DPA1 *, and DPB1 * was evaluated in 47 patients with acute lymphoblastic leukemia (ALL) and 48 with chronic myeloid leukemia (CML) for comparison with 48 healthy volunteers in Zulia, Venezuela, and to evaluate potential associations of HLA with leukemia. METHODS: Low- and high-resolution PCR-SSP was used for class II HLA regions DRB1 *, DQB1 *, DPA1 *, and DPB1 * following the instructions of KIT Olerup SSP Genovision. RESULTS: Alleles HLA-DRB1*14, especially DRB1*14:21, -DPA1*1:06, -DPA1*01:03,-DPA1*02:01, and the haplotypes HLA-DPA1*01:03-DPB1*04:01, DPA1*01:03-DPB1*02:01, DPA1*01:03-DPB1*99:01, -DRB1*14-DPA1*01:03, -DRB1*15-DPA1*01:03 were associated with CML (RR > 3); alleles HLA-DRB1*13, -DQB1*02, -DPA1*01:05, -DPA1*01:09 and the haplotypes HLA-DPA1*01:09-DPB1*02:01, DPA1*01:09-DPB1*04:01 were protective (RR < 1). Alleles HLA-DQB1*04, -DQB1*05, -DPA1*1:06, -DPA1*01:07, -DPA1*1:08 had a positive association with ALL. Alleles HLA-DPA1*01:09, -DPA1*02:01, -DPB1*02:01, -DPB1*03:01 and the haplotypes HLA-DPA1*01:03-DPB1*04:02, -DPA1*01:09-DPB1*02:01, -DPA1*01:09-DPB1*04:01, -DPA1*02:01-DPB1*04:02 were negatively associated. CONCLUSIONS: The other association patterns identified suggest marked differences in the pathogenesis of leukemia, which suggests possible deficiencies in antigen presentation for ALL or potential effects of molecular mimicry in CML.

Antecedentes: La presencia de HLA es un factor que influye en la patogénesis de las leucemias. Objetivos: Se evaluó la presencia de alelos HLA clase II DRB1*, DQB1*, DPA1* y DPB1* en 47 pacientes con leucemia linfoide aguda (LLA) y 48 con leucemia mieloide crónica (LMC), para compararlos con 48 voluntarios sanos de Zulia, Venezuela, y determinar las posibles asociaciones de HLA con las leucemias. Métodos: Se utilizó la técnica de PCR-SSP de baja y alta resolución para las regiones HLA clase II DRB1*, DQB1*, DPA1* y DPB1* conforme las instrucciones del KIT Olerup SSP Genovision. Resultados: Los alelos HLA-DRB1*14, especialmente DRB1*14:21, -DPA1*1:06, -DPA1*01:03,-DPA1*02:01, y los haplotipos HLA-DPA1*01:03-DPB1*04:01, DPA1*01:03-DPB1*02:01, DPA1*01:03-DPB1*99:01, -DRB1*14-DPA1*01:03, -DRB1*15-DPA1*01:03 tuvieron asociación con LMC (RR > 3); los alelos HLA-DRB1*13, -DQB1*02, -DPA1*01:05, -DPA1*01:09 y los haplotipos HLA-DPA1*01:09-DPB1*02:01, DPA1*01:09-DPB1*04:01 resultaron protectores (RR < 1). Los alelos HLA-DQB1*04, -DQB1*05, -DPA1*1:06, -DPA1*01:07, -DPA1*1:08 tuvieron asociación positiva con LLA. Los alelos HLA-DPA1*01:09, -DPA1*02:01, -DPB1*02:01, -DPB1*03:01 y los haplotipos HLA-DPA1*01:03-DPB1*04:02, -DPA1*01:09-DPB1*02:01, -DPA1*01:09-DPB1*04:01, -DPA1*02:01-DPB1*04:02 resultaron asociados negativamente. Conclusiones: La fuerte asociación de HLA DRB1*14 con la LMC y la ausencia de asociaciones DRB1* con LLA y los otros patrones de asociación identificados sugieren marcadas diferencias en las patogénesis de las leucemias, lo que orienta hacia posibles deficiencias en la presentación antigénica para LLA o posibles efectos de mimetismo molecular en LMC.

[Autoreactive TCD8+ lymphocytes in patients with chronic myeloid leukemia in association with HLA and adenovirus infection]. / Linfocitos TCD8+ autorreactivos en pacientes con leucemia mieloide crónica en asociación con HLA e infección con adenovirus.

BACKGROUND: A possible interaction between a specific HLA type and Adenovirus has been postulated as a promoter in leukemia clonal evolution. The HLA-DRB1*14, specifically DRB1*14:21, 14:22, 14:45, 14:26, 14:33, 14:51, 14:35 subtypes was the most frequent in CML Venezuelan patients. OBJECTIVES: It is interesting to evaluate the molecular mimicry between the Adenovirus and the DRB1*14 subtypes which exhibit the same change in the amino acid position of the DR53 epitope. This mimicked segment has been identified as a LLERRRA polypeptide. MATERIAL AND METHOD: Experimental research conducted in the IHO Venezuela, in peripheral blood samples of patients with ALL, CML and healthy controls. Mixed culture, serology, lymphocyte proliferation and cytofluorometry were performed. RESULTS: DRB1*14 patient's lymphocytes reacted in 48 hours mixed culture against DRB1*14 promoters lymphocytes exhibiting increased CD8+T lymphocytes. CML patients show a different serological profile against Adenovirus. Only CML patients reacted to LLERRRA peptide, increasing CD8+ T cells. CONCLUSION: It is established that the relationship CML, HLADRB1* 14, autoreactive CD8+ T memory cell and CD8+T specific response from Adenovirus could be at the origin of the CML in Venezuelan patients.

Antecedentes: algunos adenovirus se han señalado como activadores clonales en leucemias. El alelo HLA-DRB1* 14 subtipos DRB1*14:21, 14:22, 14:45, 14:26, 14:33, 14:51, 14:35 se asociaron con leucemia mieloide crónica (LMC) en pacientes venezolanos. Objetivo: evaluar el mimetismo molecular entre el adenovirus y la estructura del antígeno HLA-DRB1*14 que exhiben el mismo cambio en la posición de aminoácido del epítopo DR53. Material y método: estudio experimental realizado en el IHO Banco de Sangre del Estado Zulia, Venezuela en muestras de sangre periférica de pacientes con LLA, LMC y controles sanos. Se realizaron cultivo mixto de linfocitos, serología, proliferación linfocitaria y citofluorometría. Resultados: los linfocitos DRB1*14 del paciente reaccionaron en 48 horas versus los linfocitos DRB1*14 estimuladores, que exhibieron aumento de los linfocitos T CD8+. Los pacientes con LMC tuvieron un perfil serológico diferente contra el adenovirus. Sólo pacientes con LMC reaccionaron frente al péptido secuencia LLERRRA con incremento de las células TCD8+. Conclusión: se estableció que la relación leucemia mieloide crónica, HLA-DRB1*14, células TCD8+ de memoria autorreactivas y TCD8+ en respuesta específica frente al adenovirus podría estar en el origen de la leucemia mieloide crónica de pacientes venezolanos.

Efecto biológico de la recuperación nutricional en las concentraciones séricas de citocinas inflamatorias en el niño desnutrido grave / Biological effect of nutritional recovery on serum concentrations of inflammation cytokines in the malnourished child

El niño con desnutrición grave tiene una disfunción de la respuesta inmune que puede aumentar de manera significativa la morbilidad y la mortalidad por infecciones. El objetivo de la presente investigación fue evaluar el efecto de la recuperación nutricional en las concentraciones séricas de citocinas inflamatorias; tales como: interleucina 12 (IL-12), interleucina 17 (IL-17), interferón gamma (IFN-γ) y factor de necrosis tumoral alfa (TNF-α). En un estudio de tipo prospectivo y longitudinal, se seleccionó la población con base a criterios clínicos y antropométricos, constituida por 24 niños desnutridos graves en edades comprendidas entre 1 y 2 años, quienes formaban parte de un programa de recuperación nutricional. La concentración sérica de las citocinas investigadas se determinó antes y después del tratamiento nutricional, empleando la técnica de Inmunoanálisis Enzimático (ELISA) de doble anticuerpo. Para establecer comparaciones se utilizó la t de Student, y se consideró una p<0,05 como estadísticamente significante. Se observó una diferencia en las concentraciones de IL-12, IL-17, IFN-γ y TNF-α antes y después del tratamiento (p<0,05), lo cual parece indicar que la desnutrición per se provoca un estado inflamatorio y que 2 meses de apoyo nutricional intensivo, favorecen no solo la recuperación clínica del niño desnutrido grave, sino también la recuperación de su respuesta inmunitaria en cuanto a la producción de mediadores solubles como son las citocinas.

Children with severe malnutrition have a dysfunction of the immune response that can significantly increase morbidity and mortality from infections. The aim of this investigation was to evaluate the effect of nutritional recovery in serum measurements of inflammatory cytokines; such as interleukin 12 (IL-12), interleukin 17 (IL-17), interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). In a prospective and longitudinal study, 24 severe malnourished children aged between 1 and 2 years-old, who were part of a program of nutritional recovery, were selected based on clinical and anthropometric criteria. Serum measurements of cytokines were determined before and after dietary treatment, using the technique of sandwich Enzyme-Linked ImmunoSorbent Assay (ELISA). For comparisons, Student’s t test was used, considered p <0.05 as statistically significant. A difference was observed in the concentrations of IL-12, IL-17, IFN-γ and TNF-α before and after treatment (p <0.05), which suggests that malnutrition provokes an inflammatory state and two months of intensive nutritional support, not only promotes the clinical recovery of severe malnourished children, but also the recovery of the immune response with regard to the production of soluble mediators, such as cytokines.

Biological effect of nutritional recovery on serum concentrations of inflammation cytokines in the malnourished child. / Efecto biológico de la recuperación nutricional en las concentraciones séricas de citocinas inflamatorias en el niño desnutrido grave.

Children with severe malnutrition have a dysfunction of the immune response that can significantly increase morbidity and mortality from infections. The aim of this investigation was to evaluate the effect of nutritional recovery in serum measurements of inflammatory cytokines; such as interleukin 12 (IL-12), interleukin 17 (IL-17), interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). In a prospective and longitudinal study, 24 severe malnourished children aged between 1 and 2 years-old, who were part of a program of nutritional recovery, were selected based on clinical and anthropometric criteria. Serum measurements of cytokines were determined before and after dietary treatment, using the technique of sandwich Enzyme-Linked ImmunoSorbent Assay (ELISA). For comparisons, Student's t test was used, considered p <0.05 as statistically significant. A difference was observed in the concentrations of IL-12, IL-17, IFN-γ and TNF-α before and after treatment (p <0.05), which suggests that malnutrition provokes an inflammatory state and two months of intensive nutritional support, not only promotes the clinical recovery of severe malnourished children, but also the recovery of the immune response with regard to the production of soluble mediators, such as cytokines.

Mindfulness, Resilience, and Burnout Subtypes in Primary Care Physicians: The Possible Mediating Role of Positive and Negative Affect.

PURPOSE: Primary care health professionals suffer from high levels of burnout. The aim of the present study was to evaluate the associations of mindfulness and resilience with the features of the burnout types (overload, lack of development, neglect) in primary care physicians, taking into account the potential mediating role of negative and positive affect. METHODS: A cross-sectional design was used. Six hundred and twenty-two Spanish primary care physicians were recruited from an online survey. The Mindful Attention Awareness Scale (MAAS), Connor-Davidson Resilience Scale (CD-RISC), Positive and Negative Affect Schedule (PANAS), and Burnout Clinical Subtype Questionnaire (BCSQ-12) questionnaires were administered. Polychoric correlation matrices were calculated. The unweighted least squares (ULS) method was used for developing structural equation modeling. RESULTS: Mindfulness and resilience presented moderately high associations (φ = 0.46). Links were found between mindfulness and overload (γ = -0.25); resilience and neglect (γ = -0.44); mindfulness and resilience, and negative affect (γ = -0.30 and γ = -0.35, respectively); resilience and positive affect (γ = 0.70); negative affect and overload (ß = 0.36); positive affect and lack of development (ß = -0.16). The links between the burnout types reached high and positive values between overload and lack of development (ß = 0.64), and lack of development and neglect (ß = 0.52). The model was a very good fit to the data (GFI = 0.96; AGFI = 0.96; RMSR = 0.06; NFI = 0.95; RFI = 0.95; PRATIO = 0.96). CONCLUSIONS: Interventions addressing both mindfulness and resilience can influence burnout subtypes, but their impact may occur in different ways, potentially mediated by positive and negative affect. Both sorts of trainings could constitute possible tools against burnout; however, while mindfulness seems a suitable intervention for preventing its initial stages, resilience may be more effective for treating its advanced stages.

Increased cytokine/chemokines in serum from asthmatic and non-asthmatic patients with viral respiratory infection.

BACKGROUND: Respiratory viral infections can induce different cytokine/chemokine profiles in lung tissues and have a significant influence on patients with asthma. There is little information about the systemic cytokine status in viral respiratory-infected asthmatic patients compared with non-asthmatic patients. OBJECTIVES: The aim of this study was to determine changes in circulating cytokines (IL-1ß, TNF-α, IL-4, IL-5) and chemokines (MCP1: monocyte chemoattractant protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in patients with an asthmatic versus a non-asthmatic background with respiratory syncytial virus, parainfluenza virus or adenovirus respiratory infection. In addition, human monocyte cultures were incubated with respiratory viruses to determine the cytokine/chemokine profiles. PATIENTS/METHODS: Patients with asthmatic (n = 34) and non-asthmatic (n = 18) history and respiratory infections with respiratory syncytial virus, parainfluenza, and adenovirus were studied. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in blood and culture supernatants was determined by ELISA. Monocytes were isolated by Hystopaque gradient and cocultured with each of the above-mentioned viruses. RESULTS: Similar increased cytokine concentrations were observed in asthmatic and non-asthmatic patients. However, higher concentrations of chemokines were observed in asthmatic patients. Virus-infected monocyte cultures showed similar cytokine/chemokine profiles to those observed in the patients. CONCLUSIONS: Circulating cytokine profiles induced by acute viral lung infection were not related to asthmatic status, except for chemokines that were already increased in the asthmatic status. Monocytes could play an important role in the increased circulating concentration of cytokines found during respiratory viral infections.