Pulmonary Ultrasound and Diaphragmatic Shortening Fraction Combined Analysis for Extubation-Failure-Prediction in Critical Care Patients

Introduction

Invasive respiratory support is a cornerstone of Critical Care Medicine, however, protocols for withdrawal of mechanical ventilation are still far from perfect. Failure to extubation occurs in up to 20% of patients, despite a successful spontaneous breathing trial (SBT).

Functional mechanism of tracheal relaxation,antiasthmatic, and toxicological studies of 6-hydroxyflavone

Previously, we described tracheal rat rings relaxation by several flavonoids, being 6-hydroxyflavone (6-HOF) the most active derivative of the series. Thus, its mechanism of action was determined in an ex vivo tracheal rat ring bioassay. The anti-asthmatic effect was assayed in in vivo OVAlbumin (OVA)-sensitized guinea pigs. Finally, the toxicological profile of 6-HOF was studied based on Organization of Economic Cooperation and Development guidelines with modifications. 6-HOF–induced relaxation appears to be related with receptor-operated calcium channel and voltage-operated calcium channel blockade as the main mechanism of action, and also through the production of relaxant second messengers NO and cGMP. Molecular docking supports that 6-HOF acts as calcium channel blocker and by activation of nitric oxide synthase. In addition, the in vivo anti-asthmatic experiments demonstrate the dose-dependent significant anti-allergic effect of 6-HOF induced by OVA, with best activity at 50 /kg. Finally, toxicological studies determined a LD50 > 2,000 mg/kg and, after 28 day of treatment with 6-HOF (50 mg/kg) by intragastric route, mice did not exhibit evidence of any significant toxicity. In conclusion, experiments showed that 6-HOF exerts significant relaxant activity through calcium channel blockade, and possibly, by NO/cGMP-system stimulation on rat trachea, which interferes with the contraction mechanism of smooth muscle cells in the airways. In addition, the flavonoid shows potential anti-asthmatic properties in an anti-allergic pathway. Furthermore, because the pharmacological and safety evidence, we propose this flavonoid as lead for the development of a novel therapeutic agent for the treatment of asthma and related respiratory diseases.     

Lean mass and insulin resistance in women with polycystic ovary syndrome

Insulin resistance is common in women with polycystic ovary syndrome (PCOS). Muscle is the major tissue utilizing glucose while excess adipose tissue relates to insulin resistance. Thus, body composition is likely to be an important regulator of insulin sensitivity. Thirty-nine PCOS patients (age: 29.9 ± 1.0 years; BMI: 33.8 ± 1.2 kg/m²) participated in a cross sectional study. Body composition was measured by dual energy x-ray absorptiometry (DEXA). Insulin resistance and secretion were assessed using oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FS-IVGTT). In contrast with the conventional expectations, lean mass correlated directly (P < .05) with the insulin resistance measure HOMA (r = 0.440); and inversely with the insulin sensitivity index QUICKI (r = ?0.522) independent of fat mass. In 11 pairs of subjects matched for fat mass (35.6 ± 2.2 and 35.6 ± 2.4 kg) but with discordant lean mass (52.8 ± 1.8 vs 44.4 ± 1.6 kg), those with higher lean mass had a higher glucose response during OGTT (AUC_Glucose; P = .034). In contrast, 17 pairs matched for lean mass (48.7 ± 1.7 and 48.9 ± 1.6 kg) but discordant for fat mass (43.3 ± 2.6 vs 30.3 ± 8.9 kg) showed no differences in insulin resistance parameters. These novel findings indicate that lean mass relates directly to insulin resistance in PCOS.     

PaO2 increases with coughing in patients with chronic lung disease

We considered if the cyanosis frequently observed during a cough attack in patients with chronic lung disease was due to worsening hypoxemia. To investigate the effects of cough on PaO₂, we measured arterial blood gases before and after a voluntary coughing period of 45 sec, in 11 patients with Interstitial Lung Disease (ILD) and 14 patients with Chronic Obstructive Lung Disease (COPD). All patients significantly increased (p < 0.05) their PaO₂ (COPD: from 49 ± 2 to 60 ± 2 mmHg; ILD from 44 ± 2 to 51 ± 3 mmHg, mean ± SD) and decreased their PaCO₂. We conclude that stable patients with COPD and ILD increase their PaO₂ with coughing most likely due to hyperventilation. The cyanosis observed could be due to peripheral circulatory effects of coughing.     

Levels of Aflatoxin M1 in Breast Milk of Lactating Mothers in Monterrey,Mexico: Exposure and Health Risk Assessment of Newborns

The present study aimed to determine the presence of the aflatoxin M1 (AFM1) in breast milk samples from 123 nursing women and the degree of exposure of infants to this toxin, in the metropolitan area of Monterrey, Nuevo Leon state (northeast Mexico). Upon analysis, 100% of the samples were found to be contaminated with the toxin at an average concentration of 17.04 ng/L, with a range of 5.00 to 66.23 ng/L. A total of 13.01% of the breast milk samples exceeded the regulatory limit of 25 ng/L for AFM1 concentration, set by the European Union. The estimated daily intake for AFM1 and the carcinogenic risk index were also determined in the 0- to 6-, 7- to 12-, 13- to 24-, and 25- to 36-month-old age groups. The AFM1 intake through breast milk ranged from 1.09 to 20.17 ng/kg weight/day, and was higher than the tolerable daily intake, indicating a carcinogenic risk for infants in the age groups of 0- to 24-months old. This evidence demonstrates a susceptibility of breast milk to AFM1 contamination that may suggest a carcinogenic risk for the breastfed infants in Monterrey city, Nuevo Leon state, and the need to control the presence of aflatoxins in foods eaten by nursing mothers.     

Perturbed hematopoiesis in individuals with germline DNMT3A overgrowth Tatton-Brown-Rahman syndrome

Tatton-Brown-Rahman syndrome (TBRS) is an overgrowth disorder caused by germline heterozygous mutations in the DNA methyltransferase DNMT3A. DNMT3A is a critical regulator of hematopoietic stem cell (HSC) differentiation and somatic DNMT3A mutations are frequent in hematologic malignancies and clonal hematopoiesis. Yet, the impact of constitutive DNMT3A mutation on hematopoiesis in TBRS is undefined. In order to establish how constitutive mutation of DNMT3A impacts blood development in TBRS we gathered clinical data and analyzed blood parameters in 18 individuals with TBRS. We also determined the distribution of major peripheral blood cell lineages by flow cytometric analyses. Our analyses revealed non-anemic macrocytosis, a relative decrease in lymphocytes and increase in neutrophils in TBRS individuals compared to unaffected controls. We were able to recapitulate these hematologic phenotypes in multiple murine models of TBRS and identified rare hematological and non-hematological malignancies associated with constitutive Dnmt3a mutation. We further show that loss of DNMT3A in TBRS is associated with an altered DNA methylation landscape in hematopoietic cells affecting regions critical to stem cell function and tumorigenesis. Overall, our data identify key hematopoietic effects driven by DNMT3A mutation with clinical implications for individuals with TBRS and DNMT3A-associated clonal hematopoiesis or malignancies.     

Alteración de la función tiroidea en los pacientes en los que se realizó radioterapia cervical

IntroductionThe aim of this study is to determine whether the incidence of hypothyroidism in patients with Head and Neck Cancer who have undergone neck radiotherapy justifies the inclusion of thyroid function monitoring in the pre-operative and follow-up evaluation protocols.Material and methodsA retrospective study was conducted with all the patients seen in the Oncology Section of the Otorhinolaryngology Department in the “Hospital de Clínicas”, Montevideo, Uruguay, from January 1970 to May 2008. A total of 550 case records were analyzed. Of the 550 patients, 188 were excluded due to the fact they had not received radiotherapy as part of their treatment and 362 were included in the study. Of these, 55 patients had thyroid stimulating hormone (TSH) level determination after treatment with radiation therapy. Hypothyroidism was defined as a TSH value greater than or equal to 4.5 mIU/L, regardless of whether or not any symptoms were presented.Results36.4% of the patients were diagnosed as having clinical or sub-clinical hypothyroidism. The type of treatment carried out, particularly whether or not surgical resection was performed, was found to be the most significant predictive factor for the development of hypothyroidism (P=0.054).ConclusionMonitoring of the thyroid function on a six-month or annual basis, at least during the first 5 post-treatment years, has to be included in the follow-up and control protocols of every patient undergoing neck RT, and patients with TSH values over 4.5 mIU/L should be referred to the endocrinologist for hormone replacement, whether they present symptoms or not.     

Visceral Larva Migrans in Immigrants from Latin America

To determine whether increased migration is associated with an increase in incidence of toxocariasis (visceral larva migrans), we analyzed clinical data obtained from immigrants from Latin America. Although infection with Toxocara sp. roundworm larvae is distributed worldwide, seroprevalence is highest in tropical and subtropical areas.