Coronary heart disease mortality is decreasing in Argentina, and Colombia, but keeps increasing in Mexico: a time trend study.

BACKGROUND: Mortality rates due to coronary heart disease (CHD) have decreased in most countries, but increased in low and middle-income countries. Few studies have analyzed the trends of coronary heart disease mortality in Latin America, specifically the trends in young-adults and the effect of correcting these comparisons for nonspecific causes of death (garbage codes). The objective of this study was to describe and compare standardized, age-specific, and garbage-code corrected mortality trends for coronary heart disease from 1985 to 2015 in Argentina, Colombia, and Mexico. METHODS: Deaths from coronary heart disease were grouped by country, year of registration, sex, and 10-year age bands to calculate age-adjusted and age and sex-specific rates for adults aged ≥25. We corrected for garbage-codes using the methodology proposed by the Global Burden of Disease. Finally, we fitted Joinpoint regression models. RESULTS: In 1985, age-standardized mortality rates per 100,000 population were 136.6 in Argentina, 160.6 in Colombia, and 87.51 in Mexico; by 2015 rates decreased 51% in Argentina and 6.5% in Colombia, yet increased by 61% in Mexico, where an upward trend in mortality was observed in young adults. Garbage-code corrections produced increases in mortality rates, particularly in Argentina with approximately 80 additional deaths per 100,000, 14 in Colombia and 13 in Mexico. CONCLUSIONS: Latin American countries are at different stages of the cardiovascular disease epidemic. Garbage code correction produce large changes in the mortality rates in Argentina, yet smaller in Mexico and Colombia, suggesting garbage code corrections may be needed for specific countries. While coronary heart disease (CHD) mortality is falling in Argentina, modest falls in Colombia and substantial increases in Mexico highlight the need for the region to propose and implement population-wide prevention policies.

Deciphering Tacrolimus-Induced Toxicity in Pancreatic ß Cells.

ß Cell transcription factors such as forkhead box protein O1 (FoxO1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), pancreatic and duodenal homeobox 1, and neuronal differentiation 1, are dysfunctional in type 2 diabetes mellitus (T2DM). Posttransplant diabetes mellitus resembles T2DM and reflects interaction between pretransplant insulin resistance and immunosuppressants, mainly calcineurin inhibitors (CNIs). We evaluated the effect of tacrolimus (TAC), cyclosporine A (CsA), and metabolic stressors (glucose plus palmitate) on insulinoma ß cells in vitro and in pancreata of obese and lean Zucker rats. Cells were cultured for 5 days with 100 µM palmitate and 22 mM glucose; CsA (250 ng/mL) or TAC (15 ng/mL) were added in the last 48 h. Glucose plus palmitate increased nuclear FoxO1 and decreased nuclear MafA. TAC in addition to glucose plus palmitate magnified these changes in nuclear factors, whereas CsA did not. In addition to glucose plus palmitate, both drugs reduced insulin content, and TAC also affected insulin secretion. TAC withdrawal or conversion to CsA restored these changes. Similar results were observed in pancreata of obese animals on CNIs. TAC and CsA, in addition to glucose plus palmitate, induced comparable inhibition of calcineurin and nuclear factor of activated T cells (NFAT); therefore, TAC potentiates glucolipotoxicity in ß cells, possibly by sharing common pathways of ß cell dysfunction. TAC-induced ß cell dysfunction is potentially reversible. Inhibition of the calcineurin-NFAT pathway may contribute to the diabetogenic effect of CNIs but does not explain the stronger effect of TAC compared with CsA.

Urotensinergic system genes in experimental subarachnoid hemorrhage.

OBJECTIVE: Cerebral vasospasm, one of the main complications of subarachnoid hemorrhage (SAH), is characterized by arterial constriction and mainly occurs from day 4 until the second week after the event. Urotensin-II (U-II) has been described as the most potent vasoconstrictor peptide in mammals. An analysis is made of the serum U-II concentrations and mRNA expression levels of U-II, urotensin related peptide (URP) and urotensin receptor (UT) genes in an experimental murine model of SAH. DESIGN: An experimental study was carried out. SETTING: Experimental operating room of the Biomedicine Institute of Seville (IBiS), Virgen del Rocío University Hospital (Seville, Spain). PARTICIPANTS: 96 Wistar rats: 74 SAH and 22 sham intervention animals. INTERVENTIONS: Day 1: blood sampling, followed by the percutaneous injection of 100µl saline (sham) or blood (SAH) into the subarachnoid space. Day 5: blood sampling, followed by sacrifice of the animals. MAIN VARIABLES OF INTEREST: Weight, early mortality, serum U-II levels, mRNA values for U-II, URP and UT. RESULTS: Serum U-II levels increased in the SAH group from day 1 (0.62pg/mL [IQR 0.36-1.08]) to day 5 (0.74pg/mL [IQR 0.39-1.43]) (p<0.05), though not in the sham group (0.56pg/mL [IQR 0.06-0.83] day 1; 0.37pg/mL [IQR 0.23-0.62] day 5; p=0.959). Between-group differences were found on day 5 (p<0.05). The ROC analysis showed that the day 5 serum U-II levels (AUC=0.691), URP mRNA (AUC=0.706) and UT mRNA (AUC=0.713) could discriminate between sham and SAH rats. The normal serum U-II concentration range in rats was 0.56pg/mL (IQR 0.06-0.83). CONCLUSION: The urotensinergic system is upregulated on day 5 in an experimental model of SAH.

Brain injury biomarkers in the setting of cardiac surgery: Still a world to explore.

BACKGROUND: Brain injury is an important, potentially devastating, complication in cardiac surgery. A significant number of patients suffer perioperative complications involving the central nervous system. Clinical manifestations of brain injury are associated with significantly increased mortality, morbidity and health resource utilization. Serum biomarkers have been studied in cardiac surgery to measure the degree and incidence of brain injury and to improve patient management. METHODS: All relevant studies were identified by computerized searches of PubMed using the following Medical Subject Headings and keywords term: biomarker, cardiac surgery, brain injury and neurological complication. RESULTS: The biomarkers that appear to be better indicators of brain injury severity in cardiac surgery and its consequences are S100B protein, neuron-specific enolase, glial fibrillary acidic protein, tau protein, matrix metalloproteinase-9, ubiquitin C terminal hydroxylase-L1 and neurofilaments. CONCLUSIONS: These biomarkers, independently of clinical and radiological findings, show global cerebral situation at the cellular level and the degree of brain dysfunction. However, up to date, there is no biomarker entirely suitable for the detection of brain injury after cardiac surgery.

[Usefulness of biomarkers in the prognosis of severe head injuries]. / Utilidad de los biomarcadores en el pronóstico del traumatismo craneoencefálico grave.

Severe head injuries have a great socioeconomic and public health impact. Despite progress in diagnosis and treatment, no sufficiently reliable predictive models have been established for developing clinical trials and promoting effective therapeutic strategies capable of improving the prognosis. In the last decades, several brain damage biomarkers have been studied as potential diagnostic and prognostic tools in traumatic brain injury. However, all of them have limitations that preclude their universalized application. The properties of the known biomarkers -both those traditionally shown to correlate with severity and prognosis, and those recently announced as promising options- should be analyzed. New studies are needed to define their properties, both isolatedly and in combined use.

[An experimental model of mass-type brain damage in the rat: expression of brain damage based on neurospecific enolase and protein S100B]. / Modelo experimental de lesión cerebral tipo masa en rata: expresión del daño cerebral mediante enolasa neuroespecífica y proteína S100B.

OBJECTIVE: To determine whether a model of transient mass-type brain damage (MTBD) in the rat produces early release of neurospecific enolase (NSE) and protein S100B in peripheral blood, as an expression of the induced brain injury. DESIGN: An experimental study with a control group. SETTING: Experimental operating room of the Institute of Biomedicine (IBiS) of Virgen del Rocío University Hospital (Seville, Spain). PARTICIPANTS: Fourteen adult Wistar rats. INTERVENTIONS: Blood was sampled at baseline, followed by: MTBD group, a trephine perforation was used to insert and inflate the balloon of a catheter at a rate of 500 µl/20 sec, followed by 4 blood extractions every 20 min. Control group, the same procedure as before was carried out, though without trephine perforation. PRIMARY STUDY VARIABLES: Weight, early mortality, serum NSE and S100B concentration. RESULTS: Differences in NSE and S100B concentration were observed over time within the MTBD group (P<.001), though not so in the control group. With the exception of the baseline determination, differences were observed between the two groups in terms of the mean NSE and S100B values. Following MTBD, NSE and S100B progressively increased at all measurement timepoints, with r=0.765; P=.001 and r=0.628; P=.001, respectively. In contrast, the control group showed no such correlation for either biomarker. CONCLUSIONS: Serum NSE and S100B concentrations offer an early indication of brain injury affecting the gray and white matter in an experimental model of mass-type MTBD in the rat.

The higher diabetogenic risk of tacrolimus depends on pre-existing insulin resistance. A study in obese and lean Zucker rats.

Insulin resistance may interact with calcineurin inhibitors, enhancing the diabetogenic effect of tacrolimus compared with cyclosporine-A. We studied both drugs in insulin-resistant animals: obese Zucker rats (n = 45), and insulin-sensitive animals: lean Zucker rats (n = 21). During 11 days, animals received saline-buffer, cyclosporine-A (2.5 mg/kg/day) or tacrolimus (0.3 mg/kg/day). At Days 0 and 12 animals underwent intraperitoneal glucose tolerance test (0-30-60-120 min). Islet morphometry, beta-cell proliferation, apoptosis and Ins2 gene expression were analyzed. By Day 12, no lean animal had developed diabetes, while all obese animals on tacrolimus and 40% on cyclosporine-A had. In obese animals, tacrolimus reduced beta-cell proliferation and Ins2 gene expression compared with cyclosporine-A. Five days after treatment discontinuation, partial recovery was observed, with only 10% and 60% of the animals on cyclosporine and tacrolimus remaining diabetic respectively. Beta-cell proliferation increased in animals on tacrolimus while Ins2 gene expression remained unaltered. In conclusion, insulin resistance exacerbated the diabetogenic effect of tacrolimus compared with cyclosporine-A. This may be explained by greater inhibition of Ins2 gene and beta-cell proliferation by tacrolimus in the insulin resistant state. Discontinuation of the drugs may allow the recovery of the metabolic alterations.

Experimental models in traumatic brain injury: from animal models to in vitro assays. / Principales modelos experimentales de traumatismo craneoencefálico: de la preclínica a los modelos in vitro.

Traumatic brain Injury (TBI) is a major public healthcare concern, affecting people of all ages. Despite advances in the diagnosis, monitoring and clinical management of TBI, many unresolved questions remain regarding its physiopathology. In an attempt to understand the pathological features of TBI and to evaluate single potential therapeutic strategies, various animal models have been developed to simulate the mechanisms of action and the clinical manifestations of TBI patients. In turn, each model represents a specific type of trauma and evaluates a specific physiopathological aspect of the cascade triggered as a result of TBI. This review describes the main experimental models currently available referred to TBI and their possible application to the clinical setting.

Results of a multi-faceted educational intervention to prevent peripheral venous catheter-associated bloodstream infections.

Peripheral venous catheter-associated bloodstream infections (PVC-BSIs) lead to prolonged hospitalization, morbidity and increased costs. The impact of infection-prevention measures on the rate of PVC-BSIs in a university hospital in Spain was assessed. An active surveillance programme was initiated in 2015, which revealed a high PVC-BSI incidence ratio (0.48/1000 patient-days). A bundle aimed at nurses, medical staff and patients was implemented, and a Catheter Infection Team (CIT) was set up. The intervention achieved a decrease in PVC-BSI rate: 0.34 in 2016, 0.29 in 2017, and 0.17 in 2018. The decline was greatest for Gram-negative PVC-BSIs (67.6% in 2015, 35.3% in 2018).

Orthotopic Liver Transplantation: Preliminary Analysis of Complications With Grafts From Elderly Donors.

OBJECTIVE: This study aims to determine if donor grafts of patients older than 65 years develop more post-transplantation complications than those of younger patients. DESIGN: This is a retrospective, observational study of liver transplant recipients during 12 months in Virgen del Rocio University Hospital. We compare incidence rates of reperfusion syndrome, acute kidney injury, and need for intra- and postoperative red blood cell transfusions in two donor age groups in which group A is <65 years old and group B is ≥65 years old. RESULTS: Sixty cases were included. Reperfusion syndrome, acute kidney injury, and both intra- and postoperative red blood cell transfusion were more frequent in group A than group B (11.4% vs. 4%, P = .390; 44% vs. 32%, P = .423; 68.8% vs. 48%, P = .120; and 70.6% vs. 64%, P = .779, respectively). Six recipients (17.1%) died at 12 months from group A whereas there were no deaths register in group B during that time (P = .036). CONCLUSION: Our results showed that including elderly donors does not aggravate incidence of complications, emphasizing that advanced age should not be an exclusion criteria for liver transplantation.

[APACHE II and SAPS II as predictors of brain death development in neurocritical care patients]. / APACHE II y SAPS II como predictores de evolucion a muerte encefalica en pacientes neurocriticos.

AIM: To assess the prognostic value of APACHE II and SAPS II scales to predict brain death evolution of neurocritical care patients. PATIENTS AND METHODS: Retrospective observational study performed in a tertiary hospital. Include 508 patients over 16 years old, hospitalized in ICU for at least 24 hours. The variables of interest were: demographic data, risk factors, APACHE II, SAPS II and outcome. RESULTS: Median age: 41 years old (IR: 25-57). Males: 76.2%. Most frequent reason for admission: trauma (55.3%). Medians: Glasgow Coma Scale (GCS), 10 points; APACHE II, 13 points; SAPS II, 31 points; and ICU stay, 5 days. Mortality in the ICU was 28.5% (n = 145) of whom 44 (8.7%) evolved to brain death. Univariate logistic regression analysis showed that GCS, APACHE II and SAPS II scores, as well as ICU stay days behaved as predictors of brain death evolution. However, the multivariate analysis performed including APACHE II and SAPS II scores showed that only APACHE II maintained statistical significance, despite the good discrimination of both scores. CONCLUSION: Transplant coordinators might use the APACHE II score as a tool to detect patients at risk of progression to brain death, minimizing the loss of potential donors.

TITLE: APACHE II y SAPS II como predictores de evolucion a muerte encefalica en pacientes neurocriticos.Objetivo. Evaluar si las escalas pronosticas APACHE II (Acute Physiology and Chronic Health Evaluation II) y SAPS II (Simplified Acute Physiology Score II) son capaces de predecir la evolucion a muerte encefalica en pacientes neurocriticos. Pacientes y metodos. Estudio retrospectivo, observacional, realizado en un hospital de tercer nivel. Se incluyo a 508 pacientes mayores de 16 años, ingresados con patologia neurocritica aguda, con estancia en la unidad de cuidados intensivos de al menos 24 horas. Las variables de interes fueron: datos demograficos, factores de riesgo, APACHE II, SAPS II y resultado pronostico. Resultados. Mediana de edad: 41 años (rango intercuartilico: 25-57). Varones: 76,2%. Motivo de ingreso mas frecuente: traumatismo (55,3%). Medianas: escala de coma de Glasgow (GCS), 10 puntos; APACHE II, 13 puntos; SAPS II, 31 puntos; y estancia en cuidados intensivos, cinco dias. La mortalidad en la unidad de cuidados intensivos fue de 145 (28,5%). De ellos, 44 (8,7%) evolucionaron a muerte encefalica. El analisis de regresion logistica univariante mostro que la GCS, las escalas APACHE II y SAPS II, y los dias de estancia en la unidad de cuidados intensivos se comportaron como variables predictoras de evolucion a muerte encefalica. Sin embargo, en el analisis multivariante realizado con APACHE II y SAPS II, se evidencio que solo APACHE II mantiene significacion estadistica, a pesar de la buena discriminacion de ambas escalas. Conclusion. Los coordinadores de trasplantes podrian usar la escala APACHE II como una herramienta para detectar pacientes con riesgo de evolucion a muerte encefalica, minimizando la perdida de potenciales donantes.

Effects of estradiol, calcitriol and both treatments combined on bone histomorphometry in rats with chronic kidney disease and ovariectomy.

BACKGROUND: The aim of this experimental study was to analyze the histomorphometric changes observed when using different doses of estradiol, calcitriol and both treatments combined, in rats with both chronic kidney disease (CKD) and ovariectomy (OVX). METHODS: Six groups of rats with CKD+OVX were treated for 8 weeks with placebo, with different doses of 17beta-estradiol (E2), with calcitriol or with both treatments combined (E2+calcitriol). Histomorphometric studies were carried out at the proximal tibia segment. RESULTS: All groups that received active treatments showed a trabecular bone volume similar to those of rats with normal ovarian function. Treatment with E2 was effective, E2-10 diminished osteoid and eroded surfaces, and E2-30 was able to achieve a bone remodeling similar to that of the normal group. Calcitriol proved to have a positive effect on bone microarchitecture, achieving normal trabecular connectivity. The combined treatment with E2-30+calcitriol was the most effective treatment as it was not only capable of achieving normal trabecular remodeling and connectivity, but also normal trabecular bone volume. CONCLUSIONS: E2 and calcitriol seem to have independent effects on cancellous bone turnover in rats with CKD+OVX. In rats with chronic kidney disease and ovariectomy, these two agents are able to produce additive effects on bone and offer additional advantages as opposed to the use of both drugs independently.

Entheseal changes and sexual division of labor in a North-African population: The case of the pre-Hispanic period of the Gran Canaria Island (11th-15th c. CE).

The aim of this paper is to investigate the relationship between entheseal changes and sexual division of labor in the pre-Hispanic population of Gran Canaria Island (Spain). Ethnohistorical records from the period of contact between Europeans and the Canarian indigenous population provide rich information about the different activities performed by men and women. For this purpose, entheseal changes in a sample of 138 individuals (82 males and 56 females) buried in ten pre-Hispanic cemeteries (11th and 15th centuries cal. CE) were analyzed. Forty-one entheses located in the clavicle, humerus, ulna and radius were analyzed (fibrous and fibro-cartilaginous attachment sites). Entheses were graded using a visual and descriptive standard which summarized the entheseal changes. This method interprets the changes as a sign of robustness on a scale from low to high development and includes enthesopathies. The intra- and inter-observer error of this method was minimal. Sex differences in the degree of robustness, bilateral asymmetry, sexual dimorphism and principal components analyses were tested in this sample. The results indicate significant variance in the entheseal robustness between males and females. They also suggest the impact of certain biomechanical chains (pronosupination, shoulder rotation, etc.) in entheseal changes. These results contribute to an interdisciplinary approach to the study of the sexual division of labor in the pre-Hispanic society of Gran Canaria.

Hormonal replacement therapy in an animal model with chronic renal failure and ovariectomy: biochemical and densitometric study.

BACKGROUND: In spite of estrogen replacement therapy being extensively used in clinical and experimental studies without renal impairment, there are no long-term studies concerning estrogen replacement in chronic renal failure. METHODS: In this experimental study, six groups of nephrectomized and ovariectomized animals were treated with different doses of 17beta-estradiol, alone or in combination with calcitriol, to evaluate the effect of these treatments on bone metabolism. RESULTS: Biochemical results showed that estrogen alone did not have any effect neither on calcium nor on PTH serum levels. By contrast, in the groups treated with calcitriol, the levels of serum calcium were significantly higher, and the levels of iPTH were significantly lower than those observed in the control group. Animals receiving the combined treatment with estrogen and calcitriol showed the greater gain in uterus weight and a better bone mineral density at the lumbar site and the proximal and distal tibia sites. CONCLUSION: The combination of estrogen and calcitriol is the most effective therapy to prevent bone mass loss in animals with chronic renal failure and estrogen deprivation.

[Importance of estrogen insufficiency time in the efficacy of the bone response to hormonal therapy in experimental chronic renal insufficiency]. / Importancia del tiempo de insuficiencia estrogénica en la eficacia de la respuesta ósea a la terapia hormonal en la insuficiencia renal crónica experimental.

Bone disease develops relatively early in the development of CRF. The aim of this study was to evaluate the repercussion of estrogen insufficiency and the effectiveness of hormonal replacement therapy, after different periods of estrogen deprivation, on bone metabolism in an animal model with chronic renal failure and ovariectomy. A secondary purpose was to evaluate the effectiveness of bone densitometry for predicting changes in bone mass for comparison with bone histomorphometry. We used Sprague-Dawley rats with chronic renal failure and ovariectomy performed at the same time. Animals were divided into two phases according to the period of estrogen insufficiency, 4 weeks in the long estrogen insufficiency period and 1 week in the short estrogen insufficiency period. In both phases, the animals were divided into four treatment groups receiving placebo (corn oil), 17 beta-estradiol (15 micrograms/kg body weight/day), calcitriol (10 ng/kg body weight/day) or the combined treatment with estradiol and calcitriol. In both phases, a group of animals with chronic renal failure (normal ovarian function) was used as a control group. The period of treatment was 8 weeks. After this period the animals were sacrificed. This model emphasizes the importance of the period of estrogen insufficiency in the efficiency of the treatment. Four weeks of estrogen insufficiency resulted in an significant loss of trabecular bone, and less possibility of recovery. After one week of estrogen deprivation a response to the treatment was observed. The utilization of bone densitometry allowed to reproduce changes in bone mass observed afterwards by histomorphometric analysis.

[Osteoporosis, estrogens, and bone metabolism. Implications for chronic renal insufficiency]. / Osteoporosis, estrógenos y metabolismo óseo. Implicaciones en la insuficiencia renal crónica.

The relationship between estrogens, bone metabolism and osteoporosis is well known. Chronic renal failure in women is associated with menstrual disorders, lower bone mineral density and increased risk of fractures. However, most studies on renal osteodystrophy have not taken into account the role of oestrogen deficiency, its interaction, and the possible benefits of hormone replacement therapy (HRT) in uremic women. According to these limitations and the actual evidence of benefits and risks of HRT, we conclude that: a) Osteoporosis must be evaluated as a part of renal osteodystrophy; b) HRT would be considered in women with climateric symptoms and osteoporosis, and should not be used for prevention of cardiovascular disease, and c) Clearly we need to do more studies related to osteoporosis and estrogens in CRF, but right now we have to try to optimize bone turnover in our uremic patients.

[Chronic hereditary pancreatitis]. / Pancreatitis crónica hereditaria.

Hereditary chronic pancreatitis is a rare form of chronic pancreatitis transmitted by a dominant autosomal gene with incomplete penetration. We report a family with two members affected and examine clinical aspects, diagnosis and treatment of this disease.

[Spontaneous bladder perforation secondary to bacterial cystitis. Cause of acute abdomen in diabetic elderly]. / Perforación vesical espontánea secundaria a cistitis bacteriana. Causa de abdomen agudo en ancianos diabéticos.

Presentation of two clinical cases of spontaneous vesical rupture secondary to bacterial cystitis in elderly patients. One corresponds to an intraperitoneal perforation while the second case was extraperitoneal. The patients were, in both cases, diabetic women admitted in emergency due to acute abdomen. We considered that although vesical perforation secondary to bacterial cystitis is a very uncommon process, it should be taken into account in the differential diagnosis of acute abdomen in predisposed patients (diabetic elderly patients with pyuria). In such instances, a retrograde cystography would provide the diagnosis. Although extraperitoneal vesical perforations can be resolved with a vesical catheter or cystostomy, extravasation of the infected urine may result in a perivesical abscess and septic shock. Early surgical management should be considered in these cases.

[The quality of the discharge reports from the internal medicine services of Castilla-La Mancha (a structural evaluation)]. / Calidad de los informes de alta de los Servicios de Medicina Interna de Castilla-La Mancha (valoración de la estructura).

UNLABELLED: The discharge report is one of the final outputs of the health care activity. We have tried to analyze several aspects related to its quality. For this purpose, we conducted a cross-sectional study analyzing 800 reports of patients admitted in the services of Internal Medicine at 6 hospitals of Castilla-La Mancha during the year 1991. We must stress the absence of discharge reports for death patients and the failure to record drug allergies (69.9%), medical history (10.4%) and time of evolution of the disease (16.9%), as well as treatment in 17 reports out of 781 and follow-up review after discharge in 12.8%. CONCLUSIONS: Discharge reports have a low scientific content and the production of this type of records is not a routine practice in the case of death patients.