Developing Cardio-Oncology Programs in the New Era: Beyond Ventricular Dysfunction Due to Cancer Treatments.

Cardiovascular disease is a common problem in cancer patients that is becoming more widely recognized. This may be a consequence of prior cardiovascular risk factors but could also be secondary to the anticancer treatments. With the goal of offering a multidisciplinary approach to guaranteeing optimal cancer therapy and the early detection of related cardiac diseases, and in light of the recent ESC Cardio-Oncology Guideline recommendations, we developed a Cardio-Oncology unit devoted to the prevention and management of these specific complications. This document brings together important aspects to consider for the development and organization of a Cardio-Oncology program through our own experience and the current evidence.

Paraneoplastic acquired hemophilia A associated with hilar cholangiocarcinoma arising in an intraductal papillary neoplasm of the bile duct.

A 74-year-old female was admitted for painless jaundice. Laboratory tests showed hyperbilirubinemia, cholestasis, normal coagulation, and Ca19-9:163U/L. The CT-scan reported dilation of the intrahepatic and extrahepatic bile ducts secondary to a 24mm tumor in the intrapancreatic common bile duct. The magnetic cholangioresonance showed multiple endoluminal polypoid lesions, suggestive of intraductal papillary neoplasm of the bile duct (IPNB). The endoscopic bile duct brushing was non-conclusive.

Control of Peri-Implant Mucous Inflammation by Using Chlorhexidine or Ultraviolet C Radiation for Cleaning Healing Abutments. Double-Blind Randomized Clinical Trial.

Two-phase implants must be exposed to the external environment after the period of osteointegration has elapsed. For this purpose, a healing abutment is placed passing through the mucosa while forming the emergence profile. The continuous connection and disconnection can lead to an alteration in the tissue maturation, both because of the contact of bacterial plaque and because of the mechanical trauma that involves its manipulation, manifesting with different degrees of erythema or bleeding. To assess whether this epithelium disruption can be counteracted, a blinded study design was developed on 150 unitary implant patients divided into three groups (n = 50), applying chlorhexidine (group 1), ultraviolet C (UV-C) at a wavelength of 254 nm (group 2)and no treatment as a control group (group 3), during each of the disconnections and connections during the prosthodontic treatment (1 time per week for four weeks). All groups showed a better epithelium aspect at the end of the evaluation. Although there were no statistically significant differences in the degree of inflammation, the UV-C treated group had the lowest plaque accumulation, and the highest was for the chlorhexidine-treated group.

Forensic implications of the presence of chimerism after hematopoietic stem cell transplantation.

Biological vestiges are used in forensic science to resolve a large number of cases by typing the genetic profile and identifying the individual to whom it belongs. However, chimeric persons that possess cells with two or more different DNA make these types of analyses difficult. This situation can occur naturally, by errors in the fertilization or early embryogenesis, or in an artificial way, for example after hematopoietic stem cell transplantation (HSCT), when host and donor cells coexist in the patient. In this paper, we will specially focus on the latter. The vestiges from transplant patients represent a challenge from a forensic perspective since the interpretation of the genetic fingerprint can be misleading because of the presence of chimerism. Due to the high number of transplant patients (and their increase over the years) and the existence of natural chimeras (probably many of them hidden), it is necessary to consider whether we are facing a possible chimeric person or someone who has been a donor of hematopoietic stem cells in a forensic context. In this review, the presence of donor bone marrow derived cells in some tissues of forensic interest will be discussed. Finally, to emphasize the importance of chimerism after HSCT in forensic genetics, some real-life cases will be examined.

The genetic profile of bone marrow transplant patients in different samples of forensic interest.

Humans constantly lose epithelial cells, and these biological traces are frequently studied in the context of criminal investigations. The objective of this work was to examine the genetic profile in samples of forensic interest (nail and skin epithelial cells) of bone marrow transplant patients and discuss its forensic and clinical implications. The genetic profile of nail, epidermal cells and blood samples of patients receiving HSCT was analyzed by the amplification and sequencing of 38 insertion/deletion polymorphisms and 15 short tandem repeat polymorphisms. In this analysis, the age of patients and donors, the time elapsed from the transplant, the type of conditioning prior to the transplant and whether the patient suffered graft-versus-host disease were considered. Donor chimerism can be detected in the DNA extracted from nail and skin epithelial cells of transplant patients. No statistically significant correlation was found between the type of conditioning and the percentage of donor DNA in nail (p > 0.05). A positive correlation, without statistical significance, was encountered when we analyzed the relationship between the time elapsed from the transplant with the percent donor chimerism found in epithelial cells of the epidermis and in nails. We conclude that within a judicial context (e.g. when testifying as an expert witness) it is necessary to consider whether we are facing a possible transplant patient or a person who has been a bone marrow donor.

Perfil de auto anticuerpos y lactancia materna en pacientes diabéticos tipo 1 / Auto-antibody levels and history of breast-feeding in type 1 diabetic patients

Background: Islet cell-specific autoantibodies such as islet cell antibody (ICA), antiinsulin (IAA), anti-glutamic acid decarboxylase (GAD) and anti-tyrosine phosphatase (IA2) can be present in patients with type I diabetes. Breast feeding duration and the early exposure to milk substitutes are environmental factors associated to etiology of type 1 diabetes. Aim To study the frequency of the anti-GAD, anti-IA-2 e ICA antibodies in Chilean type 1 diabetic patients and determine the possible modulator effect of the breast feeding. Patients and methods: One hundred thirty four type I diabetic patients, aged one to 15 years old, were studied at the moment of their diagnosis. Patients were classified according to the duration of exclusive breast feeding. IA-2 and GAD were determined by radio immuno assay and ICA by means of indirect immunofluorescence. Results: Subjects with three months or less and those with more than three months of breast feeding were positive for ICA in 78.8 and 90.6 per cent of cases respectively, for GAD in 75 and 54.6 per cent of cases respectively (p=0.024) and for IA-2 in 73 and 43.8 per cent of cases respectively (p=0.001). All three antibodies were positive in 53.9 and 21.8 per cent of children with less or more than three months of breast feeding (p=0.001). Conclusion: Both IA-2 and GAD antibodies are less frequently positive in type 1 diabetic patients who have been breast fed for more than three months. These findings suggest a possible attenuating role of exclusive breast feeding on pancreatic aggression events in patients with type 1 diabetes

La dieta en el tratamiento de la obesidad / Diet in the treatment of obesity

Para controlar la obesidad es preciso lograr un balance energético negativo mediante la reducción de la ingesta y un aumento del gasto. La reducción de la ingesta energética debe permitir perder peso a una velocidad satisfactoria, cubriendo las necesidades de nutrientes esenciales. Se recomienda consumir 1,2 a 1,5 g de proteínas por kg de peso aceptable, según las recomendaciones ajustadas a una dieta mixta. Para cubrir las necesidades de ácidos grasos esenciales (AGE), se recomienda pequeñas cantidades de aceites de girasol u oliva (AG n-6) y el consumo de pescados grasos 2 a 3 veces por semana, además de aceite de canola, raps o soya, también en poca cantidad (AGE n-3). Los carbohidratos deben ser complejos, con un bajo índice glicémico y un elevado contenido de fibra dietética. Se destaca la necesidad de cubrir las necesidades de calcio, hierro; vitamina E (como atocoferol) vitamina C, B caroteno y otros antioxidantes, que contribuyen a la prevención de las enfermedades asociadas a la obesidad. Se concluye que la educación en nutrición orientada a lograr cambios de conducta y condiciones ambientales favorables, constituyen la base para adaptarse a un nuevo estilo de vida que permita controlar la obesidad

Asociación obesidad y leptina en tres poblaciones aborígenes de Chile / Body mass index and leptin levels in 3 Chilean aborigin populations

Background: Although there is a clear relationship between body mass index and leptin levels, few authors have addressed the possible influence of ethnic factors on these levels. Aim: To measure serum leptin in three different Chilean aboriginal populations. Subjects and methods: Fasting serum leptin and insulin levels were measured by radioimmunoassay in 345 rural mapuche individuals, 247 rural aymara subjects and 162 urban mapuche subjects. A body mass index of 27.5 kg/m2 was used as cutoff point to classify study subjects. Results: Among the three ethnic groups, women had serum leptin levels three times higher than men. In all three ethnic groups, there was a significant association between leptin levels, body mass index and gender (r2= 0.32 and 0.5 p <0.001, in rural mapuche, r2= 0.32 and 0.5 p <0.001, in aymara and r2= 0.24 and 0.49, p <0.001 in urban mapuche populations). No differences in leptin levels were observed for the interaction between age and insulin. The increments per quartile in leptin levels were lower among mapuche than aymara individuals. Conclusions: Rural mapuche individuals have a high frequency of obesity. However their leptin levels are lower than those of aymara or urban mapuche populations. The higher leptin levels observed in urban mapuche subjects could be due to environmental influences

Prevalencia de obesidad, hipertensión arterial y dislipidemia en grupos aborígenes rurales de Chile / Prevalence of obesity, hypertension and serum lipid profiles in chilean rural aboriginal communities

Background: Chilean aboriginal ethnic groups (mapuche and aymaras) have a very low prevalence rate of type 2 diabetes. The investigation of a possible relationship between this low prevalence of diabetes and obesity, hypertension and serum lipid profiles in both groups is worthwhile. Aim: To study the prevalence of obesity, hypertension and lipid profile in two chilean aboriginal communities. Subjects and Methods: The prevalence of obesity, hypertension, fasting serum total cholesterol, HDL cholesterol, triglycerides, glucose, insulin, leptin and oral glucose tolerance test were measured in 345 mapuche (106 male) and 247 aymara (100 male) individuals. Results: Sixty three percent of mapuche women, 37.9 percent of mapuche men, 39.7 percent of the aymara women and 27.0 percent of aymara men had a body mass index over 27 kg/m2. Twenty percent of mapuche men, 18.0 percent of mapuche women, 9.0 percent of aymara men and 4.8 percent of the aymara women had high blood pressure values. Serum HDL cholesterol was below 35 mg/dl in 16 percent of mapuche women, 14 percent of mapuche men, 25 percent of the aymara women and 27 percent of aymara men. No differences in total cholesterol levels were observed between mapuches and aymaras. Conclusion: Mapuche women have higher prevalence of obesity and high blood pressure than aymara women. Low serum HDL cholesterol has a higher prevalence among aymara individuals

Haplotipos HLA en familias chilenas con diabetes tipo 1 / HLA haplotypes in families with type 1 diabetes

Background: Inherited susceptibility to type 1 diabetes is partially determined by HLA genes. HLA-DQA1 and DQB1 alleles have been chosen as the most sensitive susceptibility markers. Family studies are a good method to establish specific relationship between type 1 diabetes and specific haplotypes as risk markers for the disease. Aim: To analyse the role of class II HLA molecules and the distribution of haplotypes in the genetic predisposition to type 1 diabetes in Chilean families. Material and methods: Twelve family groups constituted by 58 individuals were studied. Fourteen children (10 male) less than 15 years old with diabetes and their family members were included. The allele and haplotype frequency of the population was determined in 74 unrelated healthy children. Results: Risk haplotypes such as HLA-DR3/DQB1*0201/DQA1*0501 and HLA-DQB10302/DQA1*0501 were more common among diabetic patients and comparable to the haplotypes described in other Caucasian populations. Meanwhile, protective haplotypes found in relatives without diabetes, such as HLA-DR2/DQB1*0301/DQA1*0301 and HLA-DR8/DQB1*0402/DQA1*0301, were absent in children with diabetes. Conclusions: The general pattern of neutral or protective haplotypes, found with higher frequency in non diabetic individuals, indicates that their presence could confer protection against the disease, with a higher effect over those haplotypes associated to the disease

Polimorfismos del gen de lipoproteína lipasa en diabéticos no insulino-dependientes: estudio preliminar / Lipoprotein gene polymorphism in non dependent diabetics: preliminary study

Background: Lipoprotein lipase plays a crucial role in plasma lipoprotein metabolism. Several lipoprotein lipase gene polymorphisms have been found associated with lipid levels, premature atherosclerosis and cardiovascular disease. Aim: To investigate, in the Chilean population, the genotype distribution of lipoprotein lipase polymorphism and its possible association with lipid levels and obesity. Patients and methods: Hind III and Pvu II polymorphism was determined in 45 non-insulin-dependent diabetic patients and in 52 non diabetic controls from Santiago, Chile. Results: Hind III (+/+) polymorphism had a higher frequency in diabetics as compared to controls (0.6 and 0.29 respectively, p= 0.009). The frequency of heterozygous distribution was higher in non diabetic subjects. Controls and diabetics had comparable gene frequencies for the Pvu II genotype distribution. Analyzing the impact of these polymorphisms on plasma lipid levels, Hind III (+/+) genotype was associated with high Levels of total cholesterol and triglycerides in both groups. The hterozygote (+/-) or homozygote (-/-) state for Hind III was effectively associated with high levels of HDL cholesterol levels, as compared to the (+/+) genotype. There was no relationship between these genotypes and body mass index and waist to hip ratio. Conclusions: An association between genetic variation at the lipoprotein lipase locus with high levels of triglycerides and total cholesterol was confirmed. However, no association of these genetic markers with anthropometric measurements was found

Diabetes mellitus insulino-dependiente en Santiago de Chile: rol patogénico de factores inmunogenéticos y ambientales / Insulin-dependent diabetes mellitus in Santiago, Chile: pathogenic role of immunogenetic and environmental factors

The role of HLA class II alleles in the genetic susceptibility to develop insulin-dependent diabetes mellitus (IDDM) was examined by means of PCR and oligospecific probes in 63 IDDM children and 74 controls subjects. In diabetic patients we found a significant increase in the alleles frequency DR3, DR4, DQB1*0302 and DQA1*0301 compared to the control group, where the most prevalent alleles were DR2, DR14 (DRB1*1402), DQA1*0101 and DQA1*0201. All the risk genotypes in the diabetic group were similar than in other caucasian groups: DR3/DR4-DQB1*0201/0302-DQA1*0301/0501 and DR4/DR4-DQB1*0302/0302-DQA1*0301/0301. The homozygote character no asp57 conferred an absolute risk (AR) of 3.87 and the marker Arg52 an AR of 5.78/100.000 hab year. The homozygosis for both markers (no Asp57+Arg52) had an AR of 7.56/100.000 hab year. Regarding environmental factors associated with IDDM, our population under study showed a low prevalence of infectious agents (mainly mumps and rubella, specifically associated with IDDM) and a high prevalence of effective breast-feeding (over 3 months). These factors could be exercising a protector role in the development of IDDM. The factors that appear to be important in the low incidence of IDDM, the high percentage of breast-feeding children in the population, the reduced frequency of susceptible molecules as DR3, DQB1*0201 (compared to other caucasian groups) and the presence of protective genotypes related to DR13 and DR14 observed in the non diabetic children

Incidencia de diabetes mellitus insulino dependiente en Santiago, Chile, 1990-1993 / Incidence of insuline dependent diabetes mellitus in Santiago, Chile, 1990-1993

The aim of this study was to determine IDDM incidence in the Metropolitan Region of Chile, during the period 1990-1993 as part of the Multinational Project for Childhood Diabetes (WHO DIAMOND project group). The studied population was 1.499.784 inhabitants. All children in whom the diagnosis was made between january 1, 1990 and dec. 31, 1993 were included. We used a retrospective and prospective search and confirmation method, using as data sources public and private hospitals and medical records of pediatricians. The juvenile Diabetes Foundation was used as a secondary data source. All cases had at least two confirmation sources. A total of 176 new cases (90 males) were diagnosed in the study period, with an annual incidence of 2.92/100,000 for females and 2.95 for males. The group of children from 10 to 14 years old had the highest incidence rate (4.9/100.000), specially in women (5.25/100.000). The yearly incidence was 1.31 in 1990, 2.71 in 1991, 2.93 in 1992 and 3.7/1000,000 in 1993). It is concluded that the Metropolitan Region has one of the lowest incidences of IDDM in Latin America, although it increased along the study years

Predisposición genética para desarrollar diabetes mellitus insulino-dependiente: estudio en población de Santiago y Temuco, Chile / Genetic predisposition for developing insulin-dependent diabetes mellitus: study in population from Santiago and Temuco, Chile

Insulin dependent diabetes mellitus (IDDM) is strongly associated with particular HLA-DQ alpha/beta markers in white population. The heterodimers confirmation composed of a DQ alpha chain with an arginine at residue 52 (Arg52) combined to a DQ beta chain lacking an aspartic acid at residue 57 (non asp57) increase markedly the risk to develop IDDM. To confirm this association, 63 IDDM patients from Santiago de Chile registry, 20 IDDM patients from Temuco registry and 74 unrelated helathy non diabetic control subjects were studied. With polymerase chain reaction (PCR) and sequence specific oligonucleotide probes the individuals were typed for their HLA-DQA1 and DQB1 alleles, their DQA1/DQB1 genotype and heterodimers conformation were compared. In diabetic population both markers Arg52 homocygote and non Asp57 homocygote were increased regard to control subjects (R/R: 0.76 and 0.85 vs 0.33; ND/ND: 0.78 and 0.75 vs 0.50, p<0.05). A high relative risk (RR) was determined for both homocygote markers in IDDM groups.compared. Arg52 DQ alpha (R)/non Asp57 DQ beta (ND) heterodimers were strongly associated with susceptibility to IDDM. A high RR was observed in patients with four susceptibility DQ heterodimers (RR1: 13.7 in IDDM-Santiago and RR2: 18.6 in IDDM-Temuco, p<0.00003). The HLA-DQ alpha/beta markers and their risk heterodimers are increased in our diabetic population and could be considered as susceptibility markers to develop IDDM

Proteínas de la leche y su asociación con diabetes mellitus insulino-dependiente / Milk proteins and it association with insulin dependent diabetes mellitus

Cow`s milk has been implicated as a possible trigger of the autoinmune respose that destroys pancreatic beta cells in genetically susceptible host, thus causing diabetes mellitus. Studies in animals have suggested that bovine serum albumin, BSA, is the milk protein responsible, and an albumin peptide containing 17 amino acids, ABBOS, may be the reactive epitope. Antibodies to this peptide react with p69 a beta cell surface protein that may represent the target antigen for milk-induced beta-cell specific inmunity. The consumption of cow`s milk in Europe may support the hypothesis that cow`s milk may be a triggering factor for the development of type I diabetes. However, several epidemiological studies has not found significance correlation between the observed the importance of several enviromental factors in the devepment of type I diabetes with the objetive to establish a good prevention in susceptible subjects

Edulcorantes y productos dietéticos / Sweeteners and dietetic products

Los edulcorantes son productos útiles empleados muy comúnmente en la alimentación de los pacientes diabéticos y en regímenes hipocalóricos. Se presenta un análisis crítico de los diferentes edulcorantes calóricos y no calóricos actualmente disponibles en el mercado nacional analizando el aporte energético así como las ventajas y desventajas de cada uno de ellos. Se describen las características químicas y metabólicas del aspartame, endulzante no calórico y se comentan las investigaciones que se realizaron para lograr la autorización de su uso por la Federal Drug Administration (FDA). Se hace énfasis en que el profesional de la salud, debe tener conocimientos sobre los edulcorantes y productos dietéticos, a objeto de instruir a los pacientes para la correcta selección de ellos