Who judges medical practice?

Lawsuits due to patient perception of inappropriate medical actions are a growing reality in medical practice, which entails widespread concern in the medical community. Lawsuits often entail additional circumstances beyond the primary concern of preventing or sanctioning acts of medical negligence. CETREMI proposes various recommendations aimed at legal and medical professionals to improve this circumstance and avoid harming the doctor-patient relationship.

Las demandas judiciales por la percepción del paciente de una actuación médica inadecuada son una realidad creciente en la práctica médica, la cual entraña una preocupación extendida en el gremio médico. Las demandas judiciales frecuentemente conllevan circunstancias adicionales a la primaria preocupación de prevenir o sancionar actos de negligencia médica. CETREMI emite algunas recomendaciones a los profesionales jurídicos y médicos para mejorar esta situación y evitar daños en la relación médico-paciente.

Cord blood levels of interleukin-10 decrease in neonates with increased birth weight: novel implications of the cytokine network in early obesity.

Interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) are associated with body weight alterations in children, adolescents, and adults. However, little is known regarding the role of IL-10 and IFN-gamma in birth weight of neonates. One hundred eighty-two infants were enrolled and divided in groups of normal birth weight (< 95th percentile) or increased birth weight (> 95th percentile) for gestational age. IL-10 and IFN-gamma levels were measured in umbilical cord tissue and blood of newborns by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). The average value of birth weight in infants below and above the 95th percentile was 3.03±0.39 and 3.58±0.37 kg, respectively, and was independent of the mother's pre-gestational body mass index. The Student t test revealed that neonates with birth weights > 95th percentile show a significant 30% decrease in cord blood values of IL-10 as compared to infants with birth weights < 95th percentile (P<0.0001), with no significant changes in IFN-gamma levels (P=0.1661). Cord blood IL-10 was not of maternal origin but produced by umbilical cord tissue that showed less IL-10 expression in neonates with birth weights > 95th percentile than in infants with birth weights < 95th percentile (P=0.0252). Cord blood levels of IL-10 exhibited significant inverse correlations with birth weight (r = - 0.658, P=0.002) and INF-gamma (r = - 0.502, P=0.005).Conclusion: In conclusion, this work demonstrates for the first time that cord blood IL-10 decreases as birth weight increases in infants born at term and might help to improve early recognition of newborns at higher risk of developing obesity in childhood or adulthood. What is Known: • Reduction in interleukin-10 levels has been associated with obesity in adolescents and adults but not newborns. • The number of neonates with excess birth weight has alarmingly increased in the last 30 years. What is New: • We demonstrate that umbilical cord blood levels of interleukin-10 clearly decrease as birth weight increases. • Interleukin-10 and interferon-gamma integrate a cytokine network that might play a role in obesity in infants.

Infliximab ameliorates tumor necrosis factor-alpha-induced insulin resistance by attenuating PTP1B activation in 3T3L1 adipocytes in vitro.

Insulin resistance is the inability to respond to insulin and is considered a key pathophysiological factor in the development of type 2 diabetes. Tumor necrosis factor-alpha (TNF-alpha) can directly contribute to insulin resistance by disrupting the insulin signalling pathway via protein-tyrosine phosphatase 1B (PTP1B) activation, especially in adipocytes. Infliximab (Remicade® ) is a TNF-alpha-neutralizing antibody that has not been fully studied in insulin resistance. We investigated the effect of infliximab on TNF-alpha-induced insulin resistance in 3T3L1 adipocytes in vitro, and examined the possible molecular mechanisms involved. Once differentiated, adipocytes were cultured with 5 mmol L-1 2-deoxy-D-glucose-3 H and stimulated twice with 2 µmol L-1 insulin, in the presence or absence of 5 ng/mL TNF-alpha and/or 10 ng/mL infliximab. Glucose uptake was measured every 20 minutes for 2 hour, and phosphorylated forms of insulin receptor (IR), insulin receptor substrate-2 (IRS-2), protein kinase B (AKT) and PTP1B were determined by Western blotting. TNF-alpha-treated adipocytes showed a significant 64% decrease in insulin-stimulated glucose uptake as compared with control cells, whereas infliximab reversed TNF-alpha actions by significantly improving glucose incorporation. Although IR phosphorylation remained unaltered, TNF-alpha was able to increase PTP1B activation and decrease phosphorylation of IRS-2 and AKT. Notably, infliximab restored phosphorylation of IRS-2 and AKT by attenuating PTP1B activation. This work demonstrates for the first time that infliximab ameliorates TNF-alpha-induced insulin resistance in 3T3L1 adipocytes in vitro by restoring the insulin signalling pathway via PTP1B inhibition. Further clinical research is needed to determine the potential benefit of using infliximab for treating insulin resistance in patients.

Serum levels of interleukin-1 beta associate better with severity of simple steatosis than liver function tests in morbidly obese patients.

BACKGROUND: In high-fat diet-fed mice, interleukin-1 beta (IL-1 beta) has been shown to play a key role in hepatic steatosis. However, it remains unknown whether IL-1 beta could be associated with different grades of steatosis in obese humans. MATERIALS AND METHODS: Morbidly obese patients (n = 124) aged 18-65 years were divided into four groups: no steatosis (controls), mild steatosis, moderate steatosis, and severe steatosis using abdominal ultrasound. IL-1 beta serum levels and liver function tests were measured and significant differences were estimated by one-way ANOVA followed by Tukey test. RESULTS: IL-1 beta serum levels significantly increased in morbidly obese patients with mild (11.38 ± 2.40 pg/ml), moderate (16.72 ± 2.47 pg/ml), and severe steatosis (23.29 ± 5.2 pg/ml) as compared to controls (7.78 ± 2.26 pg/ml). Liver function tests did not significantly change among different grades of steatosis. CONCLUSION: IL-1 beta serum levels associate better with steatosis degree than liver function tests in morbidly obese population.

[Gender differences in lipocalin 2 plasmatic levels are correlated with age and the triglyceride/high-density lipoprotein ratio in healthy individuals]. / Las diferencias de género en los niveles plasmáticos de la lipocalina 2 se correlacionan con la edad y con la proporción de triglicéridos y lipoproteínas de alta densidad en individuos sanos.

INTRODUCTION: The increment of lipocalin 2, also called neutrophil gelatinase-associated lipocalin, plasmatic levels is associated with cardiometabolic and nefrologic alterations. Nonetheless, there is much controversy about lipocalin 2 plasmatic concentrations among healthy individuals. AIM: The aim of this study was to quantify lipocalin 2 in plasma of healthy men and women and to assess a possible correlation with cardiometabolic risk factors. METHODS: Fifty-three subjects (24 men and 29 women) were included. By means of an ELISA, a higher concentration of lipocalin 2 was observed in men than in women (91 ± 9 vs. 57 ± 7 ng/ml). Such difference was statistically significant (p < 0.0001). RESULTS: Lipocalin 2 levels were significantly correlated with body mass index, homeostasis model assessment index-insulin resistance index, triglycerides, high-density lipoprotein, and age. CONCLUSION: Lipocalin 2 plasmatic concentrations present a gender-specific profile in healthy subjects and its circulating levels appear to be age-dependent and associated with several cardiometabolic risk factors, including the triglycerides/high-density lipoprotein cholesterol ratio, which has proven to be a reliable marker for cardiometabolic risk among the global population.

Novel ethical dilemmas arising in geriatric clinical practice.

The purpose of this study is to determine empirically the state of the art of the medical care, when healthcare personal is confronted with ethical dilemmas related with the care they give to the geriatric population. An observational, longitudinal, prospective and qualitative study was conducted by analyzing the correlation between healthcare personnel-patient relationship, and ethical judgments regarding dilemmas that arise in daily clinical practice with geriatric patients. Mexican healthcare personnel with current active practices were asked to write up an ethical dilemma that arose frequently or that had impacted their medical practice. From the narrative input, we were able to draw up a database with 421 dilemmas, and those corresponding to patients 60 years and older were selected (n = 54, 12.8 %). The axiological analysis of the narrative dilemmas of geriatric patients was made using dialectical empiricism. The axiological analysis values found most frequently were classified into three groups: the impact of healthcare, the roles of the physician, and refusal of therapy; the healthcare role of educator, caring for the patients' life and the risk of imminent death where the values found more often. The persistence and universality of certain dilemmas in geriatrics calls for awareness and requires a good training in the ethical discernment of these dilemmas. This would help to improve substantially the care and the life quality of this population.

Association of a low-frequency variant in HNF1A with type 2 diabetes in a Latino population.

IMPORTANCE: Latino populations have one of the highest prevalences of type 2 diabetes worldwide. OBJECTIVES: To investigate the association between rare protein-coding genetic variants and prevalence of type 2 diabetes in a large Latino population and to explore potential molecular and physiological mechanisms for the observed relationships. DESIGN, SETTING, AND PARTICIPANTS: Whole-exome sequencing was performed on DNA samples from 3756 Mexican and US Latino individuals (1794 with type 2 diabetes and 1962 without diabetes) recruited from 1993 to 2013. One variant was further tested for allele frequency and association with type 2 diabetes in large multiethnic data sets of 14,276 participants and characterized in experimental assays. MAIN OUTCOME AND MEASURES: Prevalence of type 2 diabetes. Secondary outcomes included age of onset, body mass index, and effect on protein function. RESULTS: A single rare missense variant (c.1522G>A [p.E508K]) was associated with type 2 diabetes prevalence (odds ratio [OR], 5.48; 95% CI, 2.83-10.61; P = 4.4 × 10(-7)) in hepatocyte nuclear factor 1-α (HNF1A), the gene responsible for maturity onset diabetes of the young type 3 (MODY3). This variant was observed in 0.36% of participants without type 2 diabetes and 2.1% of participants with it. In multiethnic replication data sets, the p.E508K variant was seen only in Latino patients (n = 1443 with type 2 diabetes and 1673 without it) and was associated with type 2 diabetes (OR, 4.16; 95% CI, 1.75-9.92; P = .0013). In experimental assays, HNF-1A protein encoding the p.E508K mutant demonstrated reduced transactivation activity of its target promoter compared with a wild-type protein. In our data, carriers and noncarriers of the p.E508K mutation with type 2 diabetes had no significant differences in compared clinical characteristics, including age at onset. The mean (SD) age for carriers was 45.3 years (11.2) vs 47.5 years (11.5) for noncarriers (P = .49) and the mean (SD) BMI for carriers was 28.2 (5.5) vs 29.3 (5.3) for noncarriers (P = .19). CONCLUSIONS AND RELEVANCE: Using whole-exome sequencing, we identified a single low-frequency variant in the MODY3-causing gene HNF1A that is associated with type 2 diabetes in Latino populations and may affect protein function. This finding may have implications for screening and therapeutic modification in this population, but additional studies are required.

Promoting networks between evidence-based medicine and values-based medicine in continuing medical education.

BACKGROUND: In recent years, medical practice has followed two different paradigms: evidence-based medicine (EBM) and values-based medicine (VBM). There is an urgent need to promote medical education that strengthens the relationship between these two paradigms. This work is designed to establish the foundations for a continuing medical education (CME) program aimed at encouraging the dialogue between EBM and VBM by determining the values relevant to everyday medical activities. METHODS: A quasi-experimental, observational, comparative, prospective and qualitative study was conducted by analyzing through a concurrent triangulation strategy the correlation between healthcare personnel-patient relationship, healthcare personnel's life history, and ethical judgments regarding dilemmas that arise in daily clinical practice.In 2009, healthcare personnel working in Mexico were invited to participate in a free, online clinical ethics course. Each participant responded to a set of online survey instruments before and after the CME program. Face-to-face semi-structured interviews were conducted with healthcare personnel, focusing on their views and representations of clinical practice. RESULTS: The healthcare personnel's core values were honesty and respect. There were significant differences in the clinical practice axiology before and after the course (P <0.001); notably, autonomy climbed from the 10th (order mean (OM) = 8.00) to the 3rd position (OM = 5.86). In ethical discernment, the CME program had an impact on autonomy (P ≤0.0001). Utilitarian autonomy was reinforced in the participants (P ≤0.0001). Regarding work values, significant differences due to the CME intervention were found in openness to change (OC) (P <0.000), self-transcendence (ST) (P <0.001), and self-enhancement (SE) (P <0.019). Predominant values in life history, ethical discernment and healthcare personnel-patient relation were beneficence, respect and compassion, respectively. CONCLUSIONS: The healthcare personnel participating in a CME intervention in clinical ethics improved high-order values: Openness to change (OC) and Self Transcendence (ST), which are essential to fulfilling the healing ends of medicine. The CME intervention strengthened the role of educators and advisors with respect to healthcare personnel. The ethical values developed by healthcare professionals arise from their life history and their professional formation.

Aleatory Trypanosoma cruzi Vertical Transmission in Chiapas, Mexico: A Case Report.

Congenital Chagas disease is considered a form of dispersion of Trypanosoma cruzi related to human migration from endemic, often rural to previously non-endemic urban areas. This fact increases the Chagas disease establishment risk inside of family members by vertical transmission pathway. Congenital Chagas disease cases in newborns could not identified by the health professional even in endemic regions. Here we present the first family cluster of Chagas disease cases from Chiapas: one of the most important endemic areas in South of Mexico, where vertical T. cruzi transmission incidence rate is ranged between 2% to 22% revealing an important public health problem. Two cases inside a family from Chiapas, México with positive antibodies against T. cruzi detected by ELISA are presented; one of them got the infection through vertical pathway. We think that congenital Chagas disease should not be ignored in a newborn born from an asymptomatic Chagas disease mother, who may transmit the parasite infection randomly.

Two novel variants in DYRK1B causative of AOMS3: expanding the clinical spectrum.

BACKGROUND: We investigated pathogenic DYRK1B variants causative of abdominal obesity-metabolic syndrome 3 (AOMS3) in a group of patients originally diagnosed with type 2 diabetes. All DYRK1B exons were analyzed in a sample of 509 unrelated adults with type 2 diabetes and 459 controls, all belonging to the DMS1 SIGMA-cohort (ExAC). We performed in silico analysis on missense variants using Variant Effect Predictor software. To evaluate co-segregation, predicted pathogenic variants were genotyped in other family members. We performed molecular dynamics analysis for the co-segregating variants. RESULTS: After filtering, Mendelian genotypes were confirmed in two probands bearing two novel variants, p.Arg252His and p.Lys68Gln. Both variants co-segregated with the AOMS3 phenotype in classic dominant autosomal inheritance with full penetrance. In silico analysis revealed impairment of the DYRK1B protein function by both variants. For the first time, we describe age-dependent variable expressivity of this entity, with central obesity and insulin resistance apparent in childhood; morbid obesity, severe hypertriglyceridemia, and labile type 2 diabetes appearing before 40 years of age; and hypertension emerging in the fifth decade of life. We also report the two youngest individuals suffering from AOMS3. CONCLUSIONS: Monogenic forms of metabolic diseases could be misdiagnosed and should be suspected in families with several affected members and early-onset metabolic phenotypes that are difficult to control. Early diagnostic strategies and medical interventions, even before symptoms or complications appear, could be useful.

Low Serum Interleukin-6 Is a Differential Marker of Obesity-Related Metabolic Dysfunction in Women and Men.

There is scant information regarding the role of interleukin (IL)-6 in obesity-related metabolic dysfunction in humans. Thus, we studied the serum levels of IL-6 in normal weight, overweight, and obese subjects, and examined associations of IL-6 with hyperglycemia, insulin resistance, dyslipidemia, and systemic inflammation. One hundred three women and men were included in the study. Anthropometric parameters, blood glucose, insulin, total cholesterol, and triglycerides were measured. Serum levels of tumor necrosis factor-alpha (TNF-alpha), IL-10, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). One-way analysis of variance (ANOVA) showed a 2.5-fold significant decrease in serum IL-6 in overweight and obese individuals when compared with normal weight controls. Serum IL-6 exhibited significant inverse correlations with body mass index (r = -0.39/P < 0.0001), waist circumference (r = -0.42/P < 0.001), blood glucose (r = -0.40/P < 0.0001), triglycerides (r = -0.34/P < 0.0001), and TNF-alpha (r = -0.48/P < 0.0001), whereas a strongly positive correlation was found with IL-10 (r = 0.77/P < 0.0001). Multiple linear regression analysis revealed that behavior of IL-6 was mainly influenced by IL-10 (beta = 0.28/P = 1.95 × 10-6), TNF-alpha (beta = -0.67/P = 0.0017), and body fat percentage (beta = -5.95/P = 7.67 × 10-5) in women. In contrast, IL-10 (beta = 0.37/P = 1.34 × 10-9), TNF-alpha (beta = -0.85/P = 0.0005), and triglycerides (beta = 1.07/P = 0.0007) were major influencing factors of IL-6 in men. This study demonstrates that IL-6 is a marker of metabolic dysfunction that is differentially regulated in obese women and men. [Figure: see text].

A Single 48 mg Sucralose Sip Unbalances Monocyte Subpopulations and Stimulates Insulin Secretion in Healthy Young Adults.

Sucralose is a noncaloric artificial sweetener that is widely consumed worldwide and has been associated with alteration in glucose and insulin homeostasis. Unbalance in monocyte subpopulations expressing CD11c and CD206 hallmarks metabolic dysfunction but has not yet been studied in response to sucralose. Our goal was to examine the effect of a single sucralose sip on serum insulin and blood glucose and the percentages of classical, intermediate, and nonclassical monocytes in healthy young adults subjected to an oral glucose tolerance test (OGTT). This study was a randomized, placebo-controlled clinical trial. Volunteers randomly received 60 mL water as placebo (n = 20) or 48 mg sucralose dissolved in 60 mL water (n = 25), fifteen minutes prior to an OGTT. Blood samples were individually drawn every 15 minutes for 180 minutes for quantifying glucose and insulin concentrations. Monocyte subsets expressing CD11c and CD206 were measured at -15 and 180 minutes by flow cytometry. As compared to controls, volunteers receiving sucralose exhibited significant increases in serum insulin at 30, 45, and 180 minutes, whereas blood glucose values showed no significant differences. Sucralose consumption caused a significant 7% increase in classical monocytes and 63% decrease in nonclassical monocytes with respect to placebo controls. Pearson's correlation models revealed a strong association of insulin with sucralose-induced monocyte subpopulation unbalance whereas glucose values did not show significant correlations. Sucralose ingestion decreased CD11c expression in all monocyte subsets and reduced CD206 expression in nonclassical monocytes suggesting that sucralose does not only unbalance monocyte subpopulations but also alter their expression pattern of cell surface molecules. This work demonstrates for the first time that a 48 mg sucralose sip increases serum insulin and unbalances monocyte subpopulations expressing CD11c and CD206 in noninsulin-resistant healthy young adults subjected to an OGTT. The apparently innocuous consumption of sucralose should be reexamined in light of these results.

Cardiovascular risk factors and acculturation in Yaquis and Tepehuanos Indians from Mexico.

BACKGROUND: Cardiovascular (CV) risk factors are influenced by behavioral, cultural, and social factors, suggesting that acculturation plays a significant role in the emergency and growth of chronic disease. The objective of this study was to determine the relation between CV risk factors and the main components of acculturation, in Yaquis and Tepehuanos Indians from Mexico. METHODS: This was a cross-sectional population-based study in Yaquis and Tepehuanos communities from the Yaqui Valley in Sonora and the Sierra Madre Occidental Mountains in Durango, in northwest Mexico. Acculturation status is different in both ethnic groups, with Tepehuanos living in small and remote communities retaining their traditional lifestyle and Yaquis living in well-communicated communities that have assumed Westernized lifestyles. RESULTS: A total of 278 indigenous (120 Tepehuanos and 158 Yaquis) were randomly enrolled. Prevalence of obesity (48.1 and 6.7%, p <0.001), diabetes (18.3 and 0.83%, p <0.001), hypertriglyceridemia (43.0 and 15.0%, p <0.001), alcohol consumption (46.8 and 26.6%, p >0.001), and smoking (29.7 and 15.0%, p = 0.006) were significantly higher in Yaquis Indians. High blood pressure (6.3 and 3.3%, p = 0.40) and low HDL-cholesterol (42.4 and 34.2%, p = 0.22) were similar between Yaquis and Tepehuanos. Multivariate regression analysis adjusted by sex and age showed a significant association between calorie intake from saturated fat, but not other nutrients of customary diet, with hyperglycemia (OR 7.4, 95% CI 2.6-20.1), hypertriglyceridemia (OR 3.1, 95% CI 1.5-6.3), and obesity (OR 3.4, 95% CI 1.6-10.1). CONCLUSIONS: Among the components of acculturation, intake of saturated fat is the most strongly associated with the development of CV risk factors.

[Cardiovascular risk factors associated to abdominal obesity in apparently healthy subjects]. / Factores de riesgo cardiovascular asociados a obesidad abdominal en adultos aparentemente sanos.

OBJECTIVE: to determine the relationship between the abdominal obesity and cardiovascular risk factors in apparently healthy subjects from Mexico City. METHODS: a total of 186 apparently healthy men and nonpregnant women from Mexico City, were enrolled in a cross-sectional study. A detailed medical history and physical examination were performed. Abdominal obesity was defined by waist circumference > or = 80 cm for women and > or = 90 cm for men. RESULTS: a total of 125 women (67.2 %) and 61 men (32.8 %) were enrolled. Of them, 151 (81.2 %) had insulin resistance and 130 (69.9 %) abdominal obesity. Among obese subjects 96 (46.2 %) showed metabolic syndrome. There were a high prevalence of hypertriglyceridemia (31 %) and low serum levels of HDL-cholesterol (58 %). CONCLUSIONS: the used cut point for abdominal obesity, despite identifying a high proportion of subjects with cardiovascular risk, did not recognize a high proportion of subjects with disorders in their lipid profile.

High-Density Lipoprotein Reduction Differentially Modulates to Classical and Nonclassical Monocyte Subpopulations in Metabolic Syndrome Patients and in LPS-Stimulated Primary Human Monocytes In Vitro.

The effect of metabolic syndrome on human monocyte subpopulations has not yet been studied. Our main goal was to examine monocyte subpopulations in metabolic syndrome patients, while also identifying the risk factors that could directly influence these cells. Eighty-six subjects were divided into metabolic syndrome patients and controls. Monocyte subpopulations were quantified by flow cytometry, and interleukin- (IL-) 1ß secretion levels were measured by ELISA. Primary human monocytes were cultured in low or elevated concentrations of high-density lipoprotein (HDL) and stimulated with lipopolysaccharide (LPS). The nonclassical monocyte (NCM) percentage was significantly increased in metabolic syndrome patients as compared to controls, whereas classical monocytes (CM) were reduced. Among all metabolic syndrome risk factors, HDL reduction exhibited the most important correlation with monocyte subpopulations and then was studied in vitro. Low HDL concentration reduced the CM percentage, whereas it increased the NCM percentage and IL-1ß secretion in LPS-treated monocytes. The LPS effect was abolished when monocytes were cultured in elevated HDL concentrations. Concurring with in vitro results, IL-1ß serum values significantly increased in metabolic syndrome patients with low HDL levels as compared to metabolic syndrome patients without HDL reduction. Our data demonstrate that HDL directly modulates monocyte subpopulations in metabolic syndrome.