[Cerebral gas embolism as a complication of diffuse interstitial lung disease] / Embolismo gaseoso cerebral como complicación de una enfermedad pulmonar intersticial difusa.

Introduction: Cerebral gas embolism is an unusual but extremely serious condition that occurs when air is introduced into the arterial or venous circulation of the brain. Although rare, it can lead to significant neurological deficits and even the death of the patient. Clinical Case: 76-year-old patient with pre-existing diffuse interstitial lung disease, who experienced a massive stroke due to spontaneous pneumomediastinum. Her presentation included confusion, seizures, and motor weakness. Imaging tests revealed air bubbles in the cerebral sulci and hypodense areas in the cerebellum and parietooccipitals. In addition, pneumothorax and air in the upper mediastinum were noted on chest radiographs and chest CT scan. Despite therapeutic measures such as hyperbaric oxygen, the patient unfortunately died due to multiple organ failure. Discussion: The diagnosis of cerebral gas embolism generally involves performing a cerebral computed tomography, which is highly sensitive for detecting the presence of air in the cerebral vessels. Management includes monitoring of vital and neurological signs, as well as specific measures such as airway closure, venous catheter aspiration, Trendelenburg positioning, and hyperbaric oxygen. Conclusion: Cerebral gas embolism is a potentially fatal condition that requires a brain computed tomography for diagnosis and it is vitally important to know the prevention measures to avoid the appearance of this complication and also to know the general measures to adopt when it occurs.

Introducción: La embolia gaseosa cerebral es una afección inusual pero extremadamente grave que se produce cuando se introduce aire en la circulación arterial o venosa del cerebro. Aunque poco común, puede derivar en déficits neurológicos significativos e incluso la muerte del paciente. Caso Clínico: Paciente de 76 años con una enfermedad pulmonar intersticial difusa preexistente, que experimentó un ictus masivo debido a un neumomediastino espontáneo. Su presentación incluyó confusión, convulsiones y debilidad motora. Las pruebas de imagen revelaron burbujas de aire en los surcos cerebrales y áreas hipodensas en el cerebelo y parietooccipitales. Además, se observó neumotórax y aire en el mediastino superior en las radiografías de tórax y la tomografía torácica. A pesar de las medidas terapéuticas como el oxígeno hiperbárico, la paciente lamentablemente falleció debido al fallo multiorgánico. Discusión: El diagnóstico de embolia gaseosa cerebral generalmente implica la realización de una tomografía computarizada cerebral, que es altamente sensible para detectar la presencia de aire en los vasos cerebrales. El manejo incluye el control de las constantes vitales y neurológicas, así como medidas específicas como cierre de la entrada de aire, aspiración de catéteres venosos, posicionamiento de Trendelenburg y oxígeno hiperbárico. Conclusión: La embolia gaseosa cerebral es una afección potencialmente mortal que requiere una tomografía computarizada cerebral para el diagnóstico y de vital importancia conocer las medidas de prevención para evitar la aparición de esta complicación y así mismo conocer las medidas generales a adoptar cuando ésta se presenta.

Maintenance of angiogenesis inhibition with aflibercept after progression to bevacizumab in metastatic colorectal cancer: real life study in the Valencian community.

INTRODUCTION: The second-line chemotherapy in metastatic colorectal cancer (mCRC) with FOLFIRI-aflibercept demonstrated an increase in survival compared with FOLFIRI in patients previously treated with oxaliplatin-based regimens. Few data are available in patients treated previously with bevacizumab. Our objective is to evaluate the efficacy and safety of FOLFIRI-aflibercept in second-line treatment in patients who have previously received bevacizumab. PATIENTS AND METHODS: This is a observational, retrospective study of patients with mCRC treated with FOLFIRI-aflibercept in 2nd line in eight hospitals in the Valencian Community. Survival, response, and toxicity were analyzed. RESULTS: 122 patients with a median age of 61 years were included. 89% of patients had PS 0-1. The median of PFS (progression free survival) and OS (overall survival) was 5.45 (95% CI 4.74-6.15 months) and 10.15 (95% CI 7.47-12.82 months), respectively. Disease control rate 59.8%. The most common grade 3-4 adverse events were neutropenia (13,1%) and asthenia (9%). The presence of hypertension during treatment with FOLFIRI-aflibercept was associated with a survival benefit. Median of OS was 14.45 (95% CI 11.58-17.32) in patients with hypertension vs 7.78 (95% CI 5.02-10.54) in patients without hypertension (p = .001). Our results suggest that the presence of PS 0, primary tumor surgery, metachronous metastases, and the presence of only 1 metastatic location, are favorable prognostic factors associated with better OS. CONCLUSIONS: Our results confirm the value of maintaining angiogenesis inhibition with FOLFIRI-aflibercept in mCRC after progression to a first-line treatment with bevacizumab. The development of hypertension during treatment is a possible predictive marker of response.

Daltonization or colour enhancement: potential uses and limitations [Invited].

The main perceptual-cognitive limitations of CDOs (Colour Deficient Observers) are analysed, along with the uses and limitations of tools that either transform images so that CNOs (Colour Normal Observers) see them as CDOs (simulation) or transform images so that CDOs can use them as CNOs (daltonization). The four main uses of colour (comparative, denotative, connotative, and aesthetic) are analysed, along with their relation to, alternatively, the ability to discriminate colour stimuli or to categorize colours. These uses of colour are applied to analyse the possible effects of daltonization tools.

Implementation of an Algorithm of Cohort Classification to Prevent the Spread of COVID-19 in Nursing Homes.

Older adults living in nursing homes are the most vulnerable group of the COVID-19 pandemic. There are many difficulties in isolating residents and limiting the spread in this setting. We have developed a simple algorithm with a traffic light format for resident classification and sectorization within nursing homes, based on basic diagnostic tests, surveillance of symptoms onset, and close contact monitoring. We have implemented the algorithm in several centers with good data on adherence. Suggestions for implementation and evaluation are discussed.

New method for isolation of rat lamina propria macrophages in colonic tissue.

Studies on intestinal cells in the lamina propria are important for understanding the cellular and immune responses in the gut. There is a lack of specific isolating procedures of macrophage cells in rats. Two different procedures of macrophage isolation of the lamina propria in rats are compared: a standard mice protocol for lymphocyte isolation (A) adapted to rat samples and a new protocol developed specifically for rats (B). Significant differences are observed when analyzing the effect of the isolation method on the cell number, viability and phenotype. This has important implications when further functional studies are required.

Polymorphisms of the farnesyl diphosphate synthase gene modulate bone changes in response to atorvastatin.

Although their primary therapeutic indications are different, aminobisphosphonates and statins target enzymes in the mevalonate pathway, which is critical for bone homeostasis. Previous studies have shown that some polymorphisms of the gene encoding farnesyl diphosphate synthase (FDPS), the main target of aminobisphosphonates, modulate the response to these drugs. In this study, we explored whether those single nucleotide polymorphisms (SNPs) also influence the changes in bone mineral density (BMD) following therapy with statins. Sixty-six patients with coronary heart disease were studied at baseline and after 1-year therapy with atorvastatin. BMD was measured by DXA. Three SNPs of the FDPS gene (rs2297480, rs11264359 and rs17367421) were analyzed by using Taqman assays. The results showed that there was no association between the SNPs and basal BMD. However, rs2297480 and rs11264359 alleles, which are in linkage disequilibrium, were associated with changes in hip BMD following atorvastatin therapy. Thus, patients with AA genotype at the rs2297480 locus had a 0.8 ± 0.8 % increase in BMD at the femoral neck, whereas in patients with AC/CC genotypes, BMD showed a 2.3 ± 0.8 % decrease (p = 0.02). Similar results were obtained regarding changes of BMD at the femoral trochanter and when alleles at the rs11264359 locus were analyzed. However, there was no association between BMD and rs17367421 alleles. In conclusion, these results suggest that polymorphisms of the FDPS gene may influence the bone response to various drugs targeting the mevalonate pathway, including not only aminobisphosphonates but also statins.

Cobertura de vacunación antigripal en niños de Montevideo en el año 2010 / Influenza vaccination coverage in children of Montevideo in 2010

En el año 2006 se realizó una encuesta en Montevideo en niños entre 6 y 23 meses que mostró una muy baja cobertura de vacunación antigripal. El objetivo del presente estudio fue evaluar la cobertura de la misma vacuna durante el año 2010, en niños de Montevideo entre 6 y 23 meses y entre 2 y 5 años. Material y métodos: estudio observacional, descriptivo en población perteneciente a ASSE (sector público) y dos mutualistas de Montevideo (sector privado). Los datos se obtuvieron a través de encuesta realizada a padres y tutores, con formulario anónimo. Se interrogó sobre las razones para vacunar y las razones para no hacerlo. Resultados: se encuestaron responsables de 650 niños, 50.5% del grupo de 6 a 23 meses y 49.5% del grupo de 2 a 5 años. Se vacunaron 453 niños (69.7%), 69% del sector privado y 70.4% del sector público. La principal razón para vacunarse fue la indicación médica y la principal para no hacerlo fue la ausencia de indicación. Discusión: es difícil lograr altas coberturas de vacunación antigripal tanto en nuestro país como en otros. En el grupo en que es posible comparar, se obtuvieron en el año 2010 mejores resultados que en el 2006. Es probable que el temor a la pandemia haya sido factor determinante. Pero siempre la indicación médica tiene un rol preponderante en lograr mejores resultados.

Levels of DKK1 in patients with acute myocardial infarction and response to atorvastatin.

The Wnt-LPR5 signalling pathway plays an important role in skeletal homeostasis, especially in regulating osteoblastic activity. Activation of this pathway is regulated by various inhibitors, including DKK1. The objective of this study was to evaluate DKK1 levels in patients with ischemic heart disease, the response to atorvastatin and the relationship with bone mass. Twenty-one patients with acute myocardial infarction and twenty-three controls with a mean age of 61 ± 9 years with acute coronary syndrome were included. Patients were allocated to low (10-20mg) and high doses (40-80 mg) of atorvastatin according to baseline levels of cholesterol and triglycerides and the index of vascular risk. Patients were studied at hospital admission (baseline) and at 12 months of follow up. DKK1 was determined in all patients at baseline and at 12 months of follow up. Densitometric studies were conducted in the lumbar spine (L2-L4) and the femoral neck and trochanter using an X-ray densitometer. Patients had higher levels of DKK1 than controls, (111 ± 41 nmol/l versus 84 ± 27 nmol/l, p=0.014). Osteoporotic patients had higher levels of DKK1 (137.5 ± 33 nmol/l versus 95.4 ± 36 nmol/l, p=0.021). Analysis of the response to atorvastatin showed reduced DKK1 levels. In conclusion, in patients with acute coronary syndrome, atorvastatin decreases DKK1 levels. This may be a previously unreported mechanism of action of atorvastatin on bone, stimulating the Wnt signalling pathway and increasing bone mass.

Atorvastatin and BMD in coronary syndrome. Role of Lys656Asn polymorphism of leptin receptor gene.

OBJECTIVES: To evaluate the effect of atorvastatin on bone mass and markers of bone remodeling in patients with acute coronary syndrome according to the Lys656Asn leptin receptor gene polymorphism. METHODS: Sixty-two patients with acute coronary syndrome were included. Patients were allocated to low and high doses of atorvastatin according to baseline levels of cholesterol and triglycerides and the index of vascular risk and were studied at hospital admission and at 12 months. Cholesterol, triglycerides, total calcium, phosphorus, magnesium, osteocalcin and urinary deoxypyridinoline were determined in all patients at baseline and at 12 months of follow up. Densitometric studies were conducted in the lumbar spine and hip. Patients with a T-score<-2.5 were considered osteoporotic. The Lys656Asn leptin receptor gene polymorphism was determined by PCR. RESULTS: Forty-two patients were Lys/Lys homozygotic and 20 Lys/Asn heterozygotic. The prevalence of osteoporosis was 31% for the Lys/Lys genotype and 27% for the Lys/Asn genotype with no significant differences between groups. There was a significant increase in bone mineral density in the lumbar spine (1.117 +/- 0.24 versus 1.135 +/- 0.24, P = 0.008) in patients with the Lys/Lys genotype. CONCLUSION: Atorvastatin increases lumbar spine bone mineral density only in patients with the Lys/Lys genotype of the Lys656Asn polymorphism.

Effect of the TNFalpha-308 G/A polymorphism on the changes produced by atorvastatin in bone mineral density in patients with acute coronary syndrome.

AIMS: To evaluate the effect of atorvastatin on bone mass and markers of bone remodeling in patients with acute coronary syndrome depending on the tumor necrosis factor-alpha (TNFalpha)-308 G/A polymorphism. METHODS: Sixty-two patients with acute coronary syndrome (35 males and 27 females), average age 60 +/- 10 years, were included. Patients were given low (10-20 mg) and high doses (40-80 mg) atorvastatin according to their baseline levels of cholesterol and triglycerides and their index of vascular risk. Patients were studied during hospital admission (baseline) and at 12 months of follow-up. Cholesterol, triglycerides, total calcium, phosphorus, magnesium, osteocalcin and urinary deoxypyridinoline were determined in all patients at baseline and at 12 months of follow-up. Densitometric studies were conducted in the lumbar spine (L(2)-L(4)), femoral neck and trochanter using an X-ray densitometer. The TNFalpha-308 G/A polymorphism was determined by the polymerase chain reaction. RESULTS: Forty-five patients were homozygous for G/G (72.5%) and 17 were heterozygous for G/A (27.5%). The prevalence of osteoporosis (T score < or = 2.5 in the lumbar spine and/or hip) was 33% for the G/G genotype and 35% for the G/A genotype, with no statistically significant differences between groups. There was a statistically significant increase in bone mineral density (BMD) in the lumbar spine (1.107 +/- 0.32 vs. 1.129 +/- 0.23; p = 0.0001) in patients with the G/G genotype. No changes were observed in patients with the G/A genotype. CONCLUSION: In patients with acute coronary syndrome, atorvastatin increases lumbar spine BMD solely in patients with the G/G genotype of the TNFalpha-308 G/A polymorphism.

Bone mineral density, bone remodeling and osteoprotegerin in patients with acute coronary syndrome.

The objective of this study was to evaluate the relationship between coronary disease and osteoporosis and determine the effect of osteoprotegerin (OPG) on bone remodeling and bone mineral density (BMD) in a group of patients with acute coronary syndrome. Eighty-three patients (52 males and 31 women) with acute coronary syndrome (75 patients with acute myocardial infarction and 8 with unstable angina) with an average age of 61+/-10 years were studied. Levels of osteocalcin, urinarydeoxypyridinoline, OPG and the receptor activator of nuclear factor-kappaB ligand (RANKL) were determined during the hospital stay. Femoral neck, trochanter and lumbar spine densitometry was carried out using a DXA densitometer. Thirty percent of patients presented osteoporosis (39% of females and 26% of males). Osteoporotic patients were older and had a lower weight and height and elevated serum levels of osteocalcin (3.6+/-2.25 2.63 versus +/-1.55, p=0.05). Levels of OPG and RANKL were similar in both groups and showed no relationship with BMD. In conclusion, no relationship was observed between the OPG/RANKL system and BMD in these patients.

Ghrelin and bone mass in postmenopausal hypertensive women.

BACKGROUND: Ghrelin, a recently discovered peptide mainly secreted by the stomach, has an orexigenic effect which stimulates secretion of the growth hormone. It also has vasodilator effects which reduce blood pressure and stimulate in vitro, bone formation. OBJECTIVES: To evaluate the effect of ghrelin on bone mass and bone remodeling markers in postmenopausal hypertensive women. MATERIAL AND METHODS: 25 postmenopausal hypertensive women, light to moderate based on the JNC-VII criteria, were studied. They had a mean age of 58 +/- 8 years, a body mass index of 28 +/- 6 and a hypertension development time of 65 +/- 84 months. Osteocalcin, PTHi, 25-vitamin D, ghrelin in serum and deoxypiridinoline in urine were determined in all patients. A lumbar spine densitometer was made (DXP Lunar, Madison, Wisc., USA). RESULTS: Diminished levels of ghrelin were observed in the osteoporotic group (40 +/- 19 vs. 78 +/- 40, p = 0.027). When the patients were separated according to ghrelin tertiles, a greater bone mass was observed in the upper tertiles, which was associated with a decrease in the urinary deoxypiridinoline. When the total population was analyzed, no relation between the ghrelin and bone mass was found, nor with any of the parameters of calcium metabolism. Only a statistically significant relation between ghrelin and deoxypiridinoline was observed (r = -0.428, p = 0.026). CONCLUSIONS: In postmenopausal hypertensive women, ghrelin may produce a protecting effect over bone mass through an anticatabolic mechanism manifested by a decrease of bone resorption.

Effects of Atorvastatin on vitamin D levels in patients with acute ischemic heart disease.

Vitamin D deficiency is a risk factor for osteoporosis and other chronic diseases, including type 1 diabetes, hypertension, metabolic syndrome, and ischemic heart disease. Cholesterol and vitamin D share the 7-dehydrocholesterol metabolic pathway. This study evaluated the possible effect of atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Eighty-three patients (52 men and 31 women) with an acute coronary syndrome (75 with acute myocardial infarction and 8 with unstable angina) were included. After diagnosis, patients received atorvastatin as secondary prevention. Serum vitamin D was measured by high-performance liquid chromatography at baseline and at 12 months. Atorvastatin treatment produced a statistically significant decrease in cholesterol and triglyceride levels and an increase in vitamin D levels (41+/-19 vs 47+/-19 nmol/L, p=0.003). Vitamin D deficiency was decreased by 75% to 57% at 12 months. In conclusion, atorvastatin increases vitamin D levels. This increase could explain some of the beneficial effects of atorvastatin at the cardiovascular level that are unrelated to cholesterol levels.

Effect of beta-blockers on bone mass and biomechanical parameters of the femoral neck in males with acute myocardial infarction.

OBJECTIVES: Evaluate the effect of cardioselective beta-blockers on bone mass and biomechanical properties of the femoral neck in males with acute myocardial infarction. METHODS: Forty males with acute myocardial infarction were studied during one year. Seventy-five percent of the patients (30 patients) were treated with cardioselective beta-blockers and 10 were not similarly treated. A hip densitometry was performed upon release and one year later. The BMD was measured in the femoral neck and in biomechanical elements obtained by DXA. RESULTS: Both groups had similar clinical conditions at the beginning of the study and after a one-year follow-up. No differences in the BMD (0.934+/-0.12 vs. 0.921+/-0.14) were observed in the group without beta-blockers or in the group with beta-blockers (0.980+/-0.12 vs. 0.977+/-0.12). No differences were observed in the measured structural parameters. CONCLUSION: The cardioselective beta-blockers do not modify bone mass or the structural bone parameters in males with acute myocardial infarction.

Epidemiological pattern and time trends in testicular germ-cell tumors: a single institution 20-year experience.

INTRODUCTION: Recent studies have suggested a rise in the incidence of testicular germ-cell tumors (TGTs) in the last years, mainly due to an increase of early stage cases. We analysed the time trends in biological features of these patients in order to confirm this tendency in our environment. MATERIALS AND METHODS: The clinical records of 136 consecutive patients with TGTs treated at a single institution over a 20-year period (1984-2003) were retrospectively reviewed. Pathological, clinical, therapeutic and outcome data were collected. Patients were allocated into four consecutive 5- year intervals and their characteristics were compared by means of the chi-squared test. The survival analysis was performed with the method of Kaplan and Meier. RESULTS: A progressive increase in the incidence of new cases, and a more frequent diagnosis of stage I versus stage II-IV disease was confirmed within this time period. It was also observed a greater use of postorchiectomy chemotherapy, mainly due to an increase in the adjuvant indications. A significant decrease in the recurrence rate was noted. Ten-year overall survival was 86.5%. There was a trend for improved outcome, but the differences among the two decades were not statistically significant. CONCLUSIONS: A real increase in the incidence of TGTs and in the proportion of early stages was confirmed. This may be due to an epidemiological change or to an earlier diagnosis. This new pattern is associated with a more frequent use of adjuvant chemotherapy and with a reduction in the relapse rate.

[Extra-pulmonary small-cell cancer: is its outcome similar to small cell lung cancer?]. / Carcinoma microcítico de localización extrapulmonar: es su curso similar a los microcíticos pulmonares?

INTRODUCTION: Extra-pulmonary small cell carcinoma (ESCC) is as a pathologic entity distinct from small cell lung carcinoma (SCLC). ESCC is considered a systemic disease in its origin, so the therapeutic approach is similar to SCLC with chemotherapy being considered in case of extensive and local disease. We present a retrospective comparison of ESCC and SCLC in our institution. MATERIAL AND METHODS: Using the tumour registry database of Hospital Universitario La Fe we reviewed 24 ESCC cases receiving attention between 1987 and 2003, and these were compared with a series of 341 patients with SCLC in the same institution. RESULTS: Of the 24 patients with ESCC 19 were men and 5 were women with an average age of 58 years (range 23 to 85). The most frequent site was the mediastinum with 58% having extensive disease. All patients but one received treatment. The therapeutic approaches were local and systemic in 13 patients, systemic alone in 6 and local alone in 4. Schedules based on platinum and etoposide were used. The median follow-up was 53 months (range 4 to 211). Median survival was 18.9 months; 30 in patients with local disease and 8 in those with extensive disease. In the SCLC series of patients, there were 336 men and 5 women; 62% having extensive disease. The median survival was 10 months; 12 months in those patients with local disease and 8 in those with extensive disease. CONCLUSIONS: The overall survival of patients with ESCC was slightly better than patients with SCLC. ESCC with local disease had a better survival outcome than SCLC with local disease. Chemotherapy is the cornerstone of the treatment, but sometimes local treatment could be sufficient.

[Extra-cranial anaplastic oligoastrocytoma development from a low-grade glioma]. / Afectación extracraneal de oligoastrocitoma anaplásico desarrollado sobre un glioma de bajo grado.

Oligodendrogliomas are primary brain tumours derived from oligodendroglial cells, or precursors, and represent 2%-5% of brain tumours. This type of glioma has a favourable prognosis compared to other brain tumours. The treatment is multidisciplinary and is based on three therapeutic arms: surgery, radiotherapy and chemotherapy. We present a patient who had received treatment previously for a lowgrade glioma and who subsequently developed an anaplastic oligoastrocytoma in the same zone together with skull and extra-cranial involvement in the disease progression.

Colonization of America by Drosophila subobscura: association between Odh gene haplotypes, lethal genes and chromosomal arrangements.

The colonization of America by Drosophila subobscura has been a unique exper iment in nature that has allowed us to explore the effects of evolution on a continental scale. To analyze this evolutionary event, nucleotide sequences of the Odh (Octanol dehydrogenase) gene were obtained for 43 lethal chromosomal lines from colonizing populations of North America and 5 from South America, in addition to 5 chromosomal lines from Europe with different viabilities and 2 from laboratory marker stocks. Since 10 different Odh haplotypes were found in America, the minimum number of colonizers would be 5 (or 3 mated females). Only one Odh haplotype was found in American O(5) inversions confirming that only one copy of this inversion was included among the sample of colonizers. The same Odh haplotypes were detected in association with the same chromosomal arrangements and with identical lethal genes in both North and South America indicating that exactly the same chromosome types reached both hemispheres. These observations indicate that the two continental colonizations are not independent. They are derived from the same colonization event. The population from which the colonization started should contain the O(5) inversion, a non-negligible frequency of the O(3+4+7) arrangement and all other arrangements found in America. So far the only populations that fulfill all these requirements are those from Greece, indicating that these populations can be considered good candidates as a starting point for an in depth analysis of the origin of the American colonization by D. subobscura.