Parental occupational exposure to organic solvents and anencephaly in Mexico

Objective: To assess the relationship between parental occupational exposure to organic solvents, and the risk of anencephaly in Mexico. Methods: A case-control study was conducted based on the registers of the Epidemiological Surveillance System for Neural Tube Defects in Mexico; 151 cases of anencephaly of ≥20 weeks’ gestation were included. A control, born alive and without any apparent congenital malformations at birth, was selected for each case in the same maternity service in which the case was born. Information on occupational exposures, lifestyle habits, reproductive history, use of medicines, supplementation with multivitamins and folic acid, was obtained by a general questionnaire; a food frequency questionnaire was also applied to obtain information of daily intake of folate and other B vitamins. Occupational exposure to organic solvents was based on job title as a proxy for exposure and analysed considering two critical periods around conception. Results: In logistic regression analysis, the odds of having a child with anencephaly was higher if the mother or the father was occupationally exposed to organic solvents during the periconceptional period, or when both parents or at least one of them were occupationally exposed during this period with an adjusted odds ratio of 2.97 (95% CI 1.36 to 6.52). Conclusions: The results support the hypothesis that both maternal and paternal occupational exposure to organic solvents can increase the probability of having a child with anencephaly.

Safety and Effectiveness of two treatment regimes with tranexamic acid to minimize inflammatory response in elective cardiopulmonary bypass patients: a randomized double-blind, dose-dependent, phase IV clinical trial

Background. In cardiopulmonary bypass (CPB) patients, fibrinolysis may enhance postoperative inflammatory response. We aimed to determine whether an additional postoperative dose of antifibrinolytic tranexamic acid (TA) reduced CPB-mediated inflammatory response (IR). Methods. We performed a randomized, double-blind, dose-dependent, parallel-groups study of elective CPB patients receiving TA. Patients were randomly assigned to either the single-dose group (40 mg/Kg TA before CPB and placebo after CPB) or the double-dose group (40 mg/Kg TA before and after CPB). Results. 160 patients were included, 80 in each group. The incident rate of IR was significantly lower in the double-dose-group TA2 (7.5% vs. 18.8% in the single-dose group TA1; P = 0.030). After adjusting for hypertension, total protamine dose and temperature after CPB, TA2 showed a lower risk of IR compared with TA1 [OR: 0.29 (95% CI: 0.10-0.83), (P = 0.013)]. Relative risk for IR was 2.5 for TA1 (95% CI: 1.02 to 6.12). The double-dose group had significantly lower chest tube bleeding at 24 hours [671 (95% CI 549-793 vs. 826 (95% CI 704-949) mL; P = 0.01 corrected-P significant] and lower D-dimer levels at 24 hours [489 (95% CI 437-540) vs. 621(95% CI: 563-679) ng/mL; P = 0.01 corrected-P significant]. TA2 required lower levels of norepinephrine at 24 h [0.06 (95% CI: 0.03-0.09) vs. 0.20(95 CI: 0.05-0.35) after adjusting for dobutamine [F = 6.6; P = 0.014 corrected-P significant]. We found a significant direct relationship between IL-6 and temperature (rho = 0.26; P < 0.01), D-dimer (rho = 0.24; P < 0.01), norepinephrine (rho = 0.33; P < 0.01), troponin I (rho = 0.37; P < 0.01), Creatine-Kinase (rho = 0.37; P < 0.01), Creatine Kinase-MB (rho = 0.33; P < 0.01) and lactic acid (rho = 0.46; P < 0.01) at ICU arrival. Two patients (1.3%) had seizure, 3 patients (1.9%) had stroke, 14 (8.8%) had acute kidney failure, 7 (4.4%) needed dialysis, 3 (1.9%) suffered myocardial infarction and 9 (5.6%) patients died. We found no significant differences between groups regarding these events. Conclusions. Prolonged inhibition of fibrinolysis, using an additional postoperative dose of tranexamic acid reduces inflammatory response and postoperative bleeding (but not transfusion requirements) in CPB patients. A question which remains unanswered is whether the dose used was ideal in terms of safety, but not in terms of effectiveness.

Intratracheal dopamine attenuates pulmonary edema and improves survival after ventilator-induced lung injury in rats

INTRODUCTION Clearance of alveolar oedema depends on active transport of sodium across the alveolar-epithelial barrier. beta-Adrenergic agonists increase clearance of pulmonary oedema, but it has not been established whether beta-agonist stimulation achieves sufficient oedema clearance to improve survival in animals. The objective of this study was to determine whether the increased pulmonary oedema clearance produced by intratracheal dopamine improves the survival of rats after mechanical ventilation with high tidal volume (HVT). METHODS This was a randomized, controlled, experimental study. One hundred and thirty-two Wistar-Kyoto rats, weighing 250 to 300 g, were anaesthetized and cannulated via endotracheal tube. Pulmonary oedema was induced by endotracheal instillation of saline solution and mechanical ventilation with HVT. Two types of experiment were carried out. The first was an analysis of pulmonary oedema conducted in six groups of 10 rats ventilated with low (8 ml/kg) or high (25 ml/kg) tidal volume for 30 or 60 minutes with or without intratracheally instilled dopamine. At the end of the experiment the animals were exsanguinated and pulmonary oedema analysis performed. The second experiment was a survival analysis, which was conducted in two groups of 36 animals ventilated with HVT for 60 minutes with or without intratracheal dopamine; survival of the animals was monitored for up to 7 days after extubation. RESULTS In animals ventilated at HVT with or without intratracheal dopamine, oxygen saturation deteriorated over time and was significantly higher at 30 minutes than at 60 minutes. After 60 minutes, a lower wet weight/dry weight ratio was observed in rats ventilated with HVT and instilled with dopamine than in rats ventilated with HVT without dopamine (3.9 +/- 0.27 versus 4.9 +/- 0.29; P = 0.014). Survival was significantly (P = 0.013) higher in animals receiving intratracheal dopamine and ventilated with HVT, especially at 15 minutes after extubation, when 11 of the 36 animals in the HVT group had died as compared with only one out of the 36 animals in the HVT plus dopamine group. CONCLUSION Intratracheal dopamine instillation increased pulmonary oedema clearance in rats ventilated with HVT, and this greater clearance was associated with improved survival.

Prevalencia y factores asociados a desnutrición entre pacientes ingresados en un hospital de media-larga estancia

OBJECTIVES To determine the prevalence of hyponutrition at admission at a mid- to long-term stay hospital. To analyze the possible factors associated to hyponutrition; the possible relationship with mortality at one month, and the treatments for hyponutrition performed. MATERIALS AND METHOD Descriptive study from the laboratory data obtained in 140 patients. For diagnosing hyponutrition, a tool based on albumin, total cholesterol, and lymphocytes levels was used. Demographical (age and gender) and clinical data (presence of pressure soars, nasogastric tube, dementia, neoplasm, previous admission to the ICU, and main diagnosis) were gathered at admission as well as the mortality at the first month. The treatments used for hyponutrition were reviewed. RESULTS patients' age was 77.1 years and 63% were females. 17.1% of the patients presented normal nutritional status, 50.7% met the criteria for mild hyponutrition, 26.4% of moderate hyponutrition, and 5.7% of severe hyponutrition. We found no association between hyponutrition and gender, nasogastric tube, soars, dementia or neoplasm, but we did so with age (P = 0.033). We found a relationship between moderate-severe hyponutrition and pressure soars (P = 0.036). We found an association between hyponutrition and mortality at one month (OR = 1.357, 95% CI 1.121 to 1.643; P = 0.02). 35.6% of the patients with moderate-severe hyponutrition received therapy for this condition (28.9% with protein supplements and 6.7% with enteral diet). CONCLUSIONS hyponutrition affects most of the patients admitted to a mid to long-term stay hospitals and is associated with higher mortality. One third of hyponutrition patients receive nutritional therapy.

Costes frente a beneficios de los suplementos nutricionales orales.

Health economics pretends to assign resources that are short in essence and that may be used for other purposes. Health costs analysis pretends to compare the pros and cons of several options among which an election can be made in order to obtain greater benefits with lower costs. The current legislation on prescription of enteral nutrition entails confusing definitions about the administration route and the requirements of home-based enteral nutrition, without a specific regulation comprising the prescription of oral supplements (OS). From the year 2000 to 2007, the consumption of homebased enteral nutrition in Andalusia increased considerably; the costs generated being multiplied by 37. Although the number of persons that daily consumed supplements was higher than the number of diets through nasogastric tube (DT) during the years evaluated, the costs derived from OS surpassed those of DT from the year 2005 due to the combination of two factors: a progressive increase in the number of persons to whom supplements were prescribed, and on the other hand the incorporation of more expensive specific formulations. The use of oral supplements seems to be cost/effective in hospitalized surgical patients (during the pre- and postsurgical period) and possibly in hospitalized malnourished elderly, especially after performing a hyponutrition screening. Although they may be effective, under other circumstances, such as ambulatory patients, studies with an adequate methodology are necessary in order to adopt clinical decisions based on evidence and cost analysis.

Nutrición, fibrosis quística y aparato digestivo

The prevalence of hyponutrition in cystic fibrosis is high although it may vary according to the different studies. Detection of hyponutrition should be done by combining different methods, depending on their availability. However, the simplest and most validated criterion is to measure at each visit the weight (and height in children) in order to calculate the body mass index and categorizing hyponutrition according to absolute criteria: in adults < 18.5 kg/m(2), and in children as percentiles of the body mass index. Worsening of the nutritional status is directly related with the decrease in lung function parameters and it has been proposed as a morbidity (and even mortality) predictive factor in people with cystic fibrosis, independently of the level of pulmonary dysfunction. Exocrine pancreatic insufficiency is present is approximately 70-90% of the patients with cystic fibrosis and the genotype-phenotype correlation is high. Most of the patients with exocrine pancreatic insufficiency tolerate a high-fat diet provided that they are treated with pancreatic enzymes at appropriate doses. The prevalence of diabetes increases with age, reaching up 40% of the cases in patients older than 30 years. Clinical liver involvement is less prevalent (it approximately affects 1/3 of the patients). Other intestinal complications such as meconial ileus, gastroesophageal reflux, obstruction of the distal intestine, or fibrosing colon disease may also condition malnourishment. In patients with cystic fibrosis, a usual high-fat diet providing 120%-150% of the recommended calories is advised. If the nutritional goals are not achieved or maintained with diet modifications, artificial supplements may be added, although the recommendation for their use has not been endorsed by solid scientific evidences. The most frequently used preparations usually are polymeric or hypercaloric. The indications for enteral (through a tube, especially gastrostomy) or parenteral nutritional support are similar to those used in other pathologies. Dietary and nutritional control should be included in a multidisciplinary program allowing the improvement of the functional capacity and the quality of life and reducing, at least from a theoretical viewpoint, the morbimortality associated to malnourishment in these patients.

Fístula gastrocolocutánea: una infrecuente complicación de la gastrostomía endoscópica percutánea

Endoscopic percutaneous gastrostomy is a safe technique although with potential complications before which the clinician has to be on alert in order to early detect them even after a long period of normal functioning. Most of them represent minor problems. Gastrocolocutaneous fistula is a rare but severe complication favored by some risk factors such as previous post-surgical adherences, deformities of the spine, or excessive gastric inflation at the time of performing the technique. We present the case of a patient with PEG with this complication that occurred after the first tube replacement. Our goal was in two senses: on the one hand, to analyze the preventive aspects and basic guidelines for a safe PEG placement to minimize the risks; on the other hand, to alert on the possible presence of this entity to prevent a progressive nutritional impairment. This complication ought to be included in the differential diagnosis of the diarrhea syndrome in the patient carrying a PEG. The diagnostic techniques of choice are radiologic tests such as CT scan and contrast media administration through the tube. Surgical therapy should be reserved to patients with acute peritonitis in order to perform a new gastrostomy.

Amplicon DNA melting analysis for the simultaneous detection of Brucella spp and Mycobacterium tuberculosis complex. Potential use in rapid differential diagnosis between extrapulmonary tuberculosis and focal complications of brucellosis.

Some sites of extrapulmonary tuberculosis and focal complications of brucellosis are very difficult to differentiate clinically, radiologically, and even histopathologically. Conventional microbiological methods for the diagnosis of extrapulmonary tuberculosis and complicated brucellosis not only lack adequate sensitivity, they are also time consuming, which could lead to an unfavourable prognosis. The aim of this work was to develop a multiplex real-time PCR assay based on SYBR Green I to simultaneously detect Brucella spp and Mycobacterium tuberculosis complex and evaluate the efficacy of the technique with different candidate genes. The IS711, bcsp31 and omp2a genes were used for the identification of Brucella spp and the IS6110, senX3-regX3 and cfp31 genes were targeted for the detection of the M. tuberculosis complex. As a result of the different combinations of primers, nine different reactions were evaluated. A test was defined as positive only when the gene combinations were capable of co-amplifying both pathogens in a single reaction tube and showed distinguishable melting temperatures for each microorganism. According to the melting analysis, only three combinations of amplicons (senX3-regX3+bcsp31, senX3-regX3+IS711 and IS6110+IS711) were visible. Detection limits of senX3-regX3+bcsp31 and senX3-regX3+IS711 were of 2 and 3 genome equivalents for M. tuberculosis complex and Brucella while for IS6110+IS711 they were of 200 and 300 genome equivalents, respectively. The three assays correctly identified all the samples, showing negative results for the control patients. The presence of multicopy elements and GC content were the components most influencing the efficiency of the test; this should be taken into account when designing a multiplex-based SYBR Green I assay. In conclusion, multiplex real time PCR assays based on the targets senX3-regX3+bcsp31 and senX3-regX3+IS711 using SYBR Green I are highly sensitive and reproducible. This may therefore be a practical approach for the rapid differential diagnosis between extrapulmonary tuberculosis and complicated brucellosis.

Comparative clinical study of different multiplex real time PCR strategies for the simultaneous differential diagnosis between extrapulmonary tuberculosis and focal complications of brucellosis

Background: Both brucellosis and tuberculosis are chronic-debilitating systemic granulomatous diseases with a high incidence in many countries in Africa, Central and South America, the Middle East and the Indian subcontinent. Certain focal complications of brucellosis and extrapulmonary tuberculosis are very difficult to differentiate clinically, biologically and radiologically. As the conventional microbiological methods for the diagnosis of the two diseases have many limitations, as well as being time-consuming, multiplex real time PCR (M RT-PCR) could be a promising and practical approach to hasten the differential diagnosis and improve prognosis. Methodology/Principal Findings: We designed a SYBR Green single-tube multiplex real-time PCR protocol targeting bcsp31 and the IS711 sequence detecting all pathogenic species and biovars of Brucella genus, the IS6110 sequence detecting Mycobacterium genus, and the intergenic region senX3-regX3 specifically detecting Mycobacterium tuberculosis complex. The diagnostic yield of the M RT-PCR with the three pairs of resultant amplicons was then analyzed in 91 clinical samples corresponding to 30 patients with focal complications of brucellosis, 24 patients with extrapulmonary tuberculosis, and 36 patients (Control Group) with different infectious, autoimmune or neoplastic diseases. Thirty-five patients had vertebral osteomyelitis, 21 subacute or chronic meningitis or meningoencephalitis, 13 liver or splenic abscess, eight orchiepididymitis, seven subacute or chronic arthritis, and the remaining seven samples were from different locations. Of the three pairs of amplicons (senX3-regX3+ bcsp3, senX3-regX3+ IS711 and IS6110+ IS711) only senX3-regX3+ IS711 was 100% specific for both the Brucella genus and M. tuberculosis complex. For all the clinical samples studied, the overall sensitivity, specificity, and positive and negative predictive values of the M RT-PCR assay were 89.1%, 100%, 85.7% and 100%, respectively, with an accuracy of 93.4%, (95% CI, 88.3—96.5%). Conclusions/Significance: In this study, a M RT-PCR strategy with species-specific primers based on senX3-regX3+IS711 sequences proved to be a sensitive and specific test, useful for the highly efficient detection of M. tuberculosis and Brucella spp in very different clinical samples. It thus represents an advance in the differential diagnosis between some forms of extrapulmonary tuberculosis and focal complications of brucellosis.

Home enteral nutrition in Spain; NADYA registry 2011-2012.

To describe the results of the home enteral nutrition (HEN) registry of the NADYA-SENPE group in 2011 and 2012. MATERIAL AND METHODS: We retrieved the data of the patients recorded from January 1st 2011 to December 31st 2012. RESULTS: There were 3021 patients in the registry during the period from 29 hospitals, which gives 65.39 per million inhabitants. 97.95% were adults, 51.4% male. Mean age was 67.64 ± 19.1, median age was 72 years for adults and 7 months for children. Median duration with HEN was 351 days and for 97.5% was their first event with HEN. Most patients had HEN because of neurological disease (57.8%). Access route was nasogastric tube for 43.5% and gastrostomy for 33.5%. Most patients had limited activity level and, concerning autonomy, 54.8% needed total help. Nutritional formula was supplied from chemist's office to 73.8% of patients and disposables, when necessary, was supplied from hospitals to 53.8% of patients. HEN was finished for 1,031 patients (34.1%) during the period of study, 56.6% due to decease and 22.2% due to recovery of oral intake. CONCLUSIONS: Data from NADYA-SENPE registry must be explained cautiously because it is a non-compulsory registry. In spite of the change in the methodology of the registry in 2010, tendencies regarding HEN have been maintained, other than oral route

Influence of the LILRA3 Deletion on Multiple Sclerosis Risk: Original Data and Meta-Analysis.

BACKGROUND Multiple sclerosis (MS) is a neurodegenerative, autoimmune disease of the central nervous system. Genome-wide association studies (GWAS) have identified over hundred polymorphisms with modest individual effects in MS susceptibility and they have confirmed the main individual effect of the Major Histocompatibility Complex. Additional risk loci with immunologically relevant genes were found significantly overrepresented. Nonetheless, it is accepted that most of the genetic architecture underlying susceptibility to the disease remains to be defined. Candidate association studies of the leukocyte immunoglobulin-like receptor LILRA3 gene in MS have been repeatedly reported with inconsistent results. OBJECTIVES In an attempt to shed some light on these controversial findings, a combined analysis was performed including the previously published datasets and three newly genotyped cohorts. Both wild-type and deleted LILRA3 alleles were discriminated in a single-tube PCR amplification and the resulting products were visualized by their different electrophoretic mobilities. RESULTS AND CONCLUSION Overall, this meta-analysis involved 3200 MS patients and 3069 matched healthy controls and it did not evidence significant association of the LILRA3 deletion [carriers of LILRA3 deletion: p = 0.25, OR (95% CI) = 1.07 (0.95-1.19)], even after stratification by gender and the HLA-DRB1*15:01 risk allele.

Clinical and epidemiological features and prognosis of complicated pyelonephritis: a prospective observational single hospital-based study.

BACKGROUND Complicated pyelonephritis (cPN), a common cause of hospital admission, is still a poorly-understood entity given the difficulty involved in its correct definition. The aim of this study was to analyze the main epidemiological, clinical, and microbiological characteristics of cPN and its prognosis in a large cohort of patients with cPN. METHODS We conducted a prospective, observational study including 1325 consecutive patients older than 14 years diagnosed with cPN and admitted to a tertiary university hospital between 1997-2013. After analyzing the main demographic, clinical and microbiological data, covariates found to be associated with attributable mortality in univariate analysis were included in a multivariate logistic regression model. RESULTS Of the 1325 patients, 689 (52%) were men and 636 (48%) women; median age 63 years, interquartile range [IQR] (46.5-73). Nine hundred and forty patients (70.9%) had functional or structural abnormalities in the urinary tract, 215 (16.2%) were immunocompromised, 152 (11.5%) had undergone a previous urinary tract instrumentation, and 196 (14.8%) had a long-term bladder catheter, nephrostomy tube or ureteral catheter. Urine culture was positive in 813 (67.7%) of the 1251 patients in whom it was done, and in the 1032 patients who had a blood culture, 366 (34%) had bacteraemia. Escherichia coli was the causative agent in 615 episodes (67%), Klebsiella spp in 73 (7.9%) and Proteus ssp in 61 (6.6%). Fourteen point one percent of GNB isolates were ESBL producers. In total, 343 patients (25.9%) developed severe sepsis and 165 (12.5%) septic shock. Crude mortality was 6.5% and attributable mortality was 4.1%. Multivariate analysis showed that an age >75 years (OR 2.77; 95% CI, 1.35-5.68), immunosuppression (OR 3.14; 95% CI, 1.47-6.70), and septic shock (OR 58.49; 95% CI, 26.6-128.5) were independently associated with attributable mortality. CONCLUSIONS cPN generates a high morbidity and mortality and likely a great consumption of healthcare resources. This study highlights the factors directly associated with mortality, though further studies are needed in the near future aimed at identifying subgroups of low-risk patients susceptible to outpatient management.

Postoperative epidural hematoma contributes to delayed upper cord tethering after decompression of Chiari malformation type I.

Symptomatic arachnoiditis after posterior fossa surgical procedures such as decompression of Chiari malformation is a possible complication. Clinical presentation is generally insidious and delayed by months or years. It causes disturbances in the normal flow of cerebrospinal fluid and enlargement of a syrinx cavity in the upper spinal cord. Surgical de-tethering has favorable results with progressive collapse of the syrinx and relief of the associated symptoms. Case Description: A 30-year-old male with Chiari malformation type I was treated by performing posterior fossa bone decompression, dura opening and closure with a suturable bovine pericardium dural graft. Postoperative period was uneventful until the fifth day in which the patient suffered intense headache and progressive loose of consciousness caused by an acute posterior fossa epidural hematoma. It was quickly removed with complete clinical recovering. One year later, the patient experienced progressive worsened of his symptoms. Upper spinal cord tethering was diagnosed and a new surgery for debridement was required. Conclusions: The epidural hematoma compressing the dural graft against the neural structures contributes to the upper spinal cord tethering and represents a nondescribed cause of postoperative fibrosis, adhesion formation, and subsequent recurrent hindbrain compression.