How kidney clock works: circadian pattern of eGFR based on a population data group.

A circadian regulation of renal function it has been described in the last few years. An intradaily variation in glomerular filtration rate (eGFR) has also been discovered at the individual level. The aim of this study was to check if there exists a circadian pattern of eGFR at population data group level and to compare the population results with those described at individual level. We have studied a total of 446,441 samples analysed in the emergency laboratories of two Spanish hospitals between January 2015 and December 2019. We selected all the records of eGFR values between 60 and 140 mL/min/1.73 m2 using CKD-EPI formula from patients between 18 and 85 years. The intradaily intrinsic eGFR pattern was computed using the extraction time of day in four nested mixed linear and sinusoidal regression models. All models showed an intradaily eGFR pattern, but the estimated model coefficients differed depending on whether age was included. The inclusion of age improved the performance of the model. In this model, the acrophase occurred at 7:46 h. We describe the distribution of eGFR values depending on the time in two different populations. This distribution is adjusted to a circadian rhythm that behaves similarly to the individual rhythm. This pattern is similar in each of the years studied from each hospital as well as between both hospitals. The results found suggest the incorporation of the concept of "population circadian rhythm" into the scientific world.

[Faecal occult blood test in symptomatic patients in primary care: A retrospective study in a healthcare area of Toledo]. / Sangre oculta en heces en pacientes sintomáticos en Atención Primaria: Un estudio retrospectivo en el área sanitaria de Toledo.

AIM: To review referral protocol in symptomatic patients from primary care of using 15µgHb/g faeces threshold with three consecutive samples in faecal occult blood (FOB) test. To compare test utility using current recommendations of 10µgHb/g faeces threshold and one sample. MATERIAL AND METHODS: A retrospective observational study was designed, including FOB samples of symptomatic patients from primary care. Samples were analyzed at the biochemistry laboratory in 2017. Seven hundred and fifteen patients tested positive and 925 patients negative. Exclusion criteria were secondary care request and patients under the age of 18. Descriptive analysis was performed of FOB results and clinical data about request and colonoscopy. FOB test's diagnostic utility was studied for different threshold (10 and 15µgHb/g faeces) in the same population. RESULTS: FOB positivity rate was 22.8% and cancer detection rate was 11%. However, the number of samples does not modify diagnostic precision. Negative predictive value is higher with 10µgHb/g faeces threshold. CONCLUSIONS: Correct patient selection and optimal threshold increase cancer detection rate. The protocol with 10µgHb/g faeces threshold and one sample collection for symptomatic patients from primary care improves the FOB test's purpose.

Intravenous thrombolysis for acute ischemic stroke in centenarians.

PURPOSE: The benefit of intravenous alteplase is well established for patients with disabling stroke symptoms regardless of age, although data on outcomes in centenarian patients are scarce. We present our experience in patients beyond 100 years. METHODS: Descriptive study including centenarians from our single-centre prospective registry who underwent intravenous thrombolysis with alteplase for acute ischemic stroke in our tertiary university hospital. Clinical variables and functional outcome at 3 months were collected. RESULTS: Four patients, all women, functionally independent (mRS ≤ 2) were included. Treatment with alteplase was applied within 4.5 h of stroke onset. One patient complicated with pneumonia and died. Two patients were functionally independent (mRS ≤ 2) at discharge, while the third was partially dependent (mRS of 3 at discharge), improving after 3 months, (mRS 2). No serious hemorrhagic or systemic adverse events were registered. CONCLUSION: In our experience, intravenous thrombolysis may be beneficial and should be considered in patients over 100 years old with no previous disability.

Contraindications to intravenous thrombolysis in prehospital triage of thrombectomy candidates.

BACKGROUND AND PURPOSE: The existence of contraindications to intravenous thrombolysis (IVT) is considered a criterion for direct transfer of patients with suspected acute stroke to thrombectomy-capable centers in the prehospital setting. Our aim was to assess the utility of this criterion in a setting where routing protocols are defined by the Madrid - Direct Referral to Endovascular Center (M-DIRECT) prehospital scale. METHODS: This was a post hoc analysis of the M-DIRECT study. Reported contraindications to IVT were retrospectively collected from emergency medical services reports and categorized into late window, anticoagulant treatment and other contraindications. Final diagnosis and treatment rates were compared between patients with and without reported IVT contraindications and according to anticoagulant treatment or late window categories. RESULTS: The M-DIRECT study included 541 patients. Reported IVT contraindications were present in 227 (42.0%) patients. Regarding final diagnosis no significant differences were found between patients with or without reported IVT contraindications: ischaemic stroke (any) 65.6% vs. 62.1%, ischaemic stroke with large vessel occlusion (LVO) 32.2% vs. 28.3%, hemorrhagic stroke 15.4% vs. 15.6%, stroke mimic 18.9% vs. 22.3% respectively. Amongst patients with LVO, endovascular thrombectomy (EVT) was performed less often in the presence of IVT contraindications (56.2% vs. 74.2%). M-DIRECT-positive patients had higher rates of LVO and EVT compared with M-DIRECT-negative patients independent of reported IVT contraindications. CONCLUSIONS: Reported IVT contraindications alone do not increase EVT likelihood and should not be considered to determine routing in urban stroke networks.

Prevalence and distribution of hepatitis C virus genotypes in Spain during the 2000-2015 period (the GEHEP 005 study).

We report the largest study on the prevalence and distribution of HCV genotypes in Spain (2000-2015), and we relate them with clinical, epidemiological and virological factors. Patients from 29 hospitals in 10 autonomous communities (Andalusia, Aragon, Castilla-Leon, Catalonia, Galicia, Canary Islands, Madrid Community, Valencian Community, Murcia Region and Basque Country) have been studied. Annual distribution of HCV genotypes and subtypes, as well as gender, age, transmission route, HIV and/or HBV coinfection, and treatment details were recorded. We included 48595 chronically HCV-infected patients with the following characteristics: median age 51 years (IQR, 44-58), 67.9% male, 19.1% HIV-coinfected, 23.5% HBV-coinfected. Parenteral transmission route was the most frequent (58.7%). Genotype distribution was 66.9% GT1 (24.9% subtype 1a and 37.9% subtype 1b), 2.8% GT2, 17.3% GT3, 11.4% GT4 and 0.1% GT5 and 0.02% GT6. LiPA was the most widely HCV genotyping test used (52.4%). HCV subtype 1a and genotypes 3 and 4 were closely associated with male gender, parenteral route of infection and HIV and HBV coinfection; in contrast, subtype 1b and genotype 2 were associated with female gender, nonparenteral route and mono-infection. Age was related to genotype distribution, and different patterns of distribution and biodiversity index were observed between different geographical areas. Finally, we describe how treatment and changes in transmission routes may have affected HCV genotype prevalence and distribution patterns. We present the most recent data on molecular epidemiology of hepatitis C virus in Spain. This study confirms that genotype distributions vary with age, sex, HIV and HBV coinfection and within geographical areas and epidemiological groups.

Use of a closed-system drug transfer device (PhaSeal) and impact on preparation time.

PhaSeal is a closed-system drug transfer device which has demonstrated to protect against occupational exposure to antineoplastic agents. Our aim was to assess the impact of the incorporation of PhaSeal on the processing time of chemotherapy. The study was a prospective simulation study which compared the processing times with the traditional open-system technique and using the closed-transfer system. Four experienced pharmacy technicians prepared six batches with each method simulating simple chemotherapy admixture operations. We compared the mean times obtained by student's t test and evaluated the "learning effect" between days by ANOVA. The average percentage of time saving with PhaSeal was 31.7% (time per batch [mean +/- SD] 6.44+0.73 vs. 9.44+0.98 minutes). Mean difference was statistically significant (3.0 min IC95% 2.50-3.50; p>0.0001). No significant learning curve effect was detected. The BD Medical/Carmel Pharma PhaSeal system, in addition to its protective properties, is able to save time in the elaboration process which leads to organization advantages for hospital pharmacy services.

HEPATIC LESIONS IN CATTLE GRAZING ON Brachiaria decumbens IN MESETAS, META (COLOMBIA) / LESIONES HEPÁTICAS EN BOVINOS MANTENIDOS EN PASTURAS DE Brachiaria decumbens EN MESETAS, META (COLOMBIA)

Brachiaria spp. is the predominate pasture grass for cattle grazing in the Orinoco watershed in Colombia. However, it has been recognized that this grass can cause liver damage, leading to photosensitization in ruminants; such injury is caused by the steroidal saponins found in this plant. Liver samples taken from five clinically-healthy bulls' left and right liver lobes and portal vein entrance were processed by routine histological techniques to evaluate liver lesions caused by Brachiaria decumbens in cattle grazing on Colombia's Eastern plains. The main lesions observed in these tissues were mononuclear cell cholangiohepatitis, foamy macrophages, moderate bile pigment accumulation, hepatocyte death, binucleated hepatocytes, moderate bile duct hyperplasia and multiple foci of mild fibrosis in portal areas; these were corroborated by Masson's trichrome staining. Such lesions were predominantly distributed at the portal vein entrance, frequently being located in the periportal region. This type of lesion has usually been attributed to Brachiaria decumbens consumption, and was present in clinically healthy animals exclusively feeding on this type of grass. Thus we conclude that the tissue alterations found herein were caused by Brachiaria decumbens. This research should be expanded to involve a larger selection of cattle populations, throughout a broader geographical region.

En la Orinoquía colombiana hay una considerable cantidad de ganado bovino que se alimenta predominantemente de Brachiaria spp. Sin embargo, se ha reconocido que esta pastura puede ocasionar daño hepático y posterior fotosensibilización en rumiantes, por las saponinas esteroidales que contiene. Con el propósito de evaluar las lesiones hepáticas en ganado bovino procedente de los Llanos Orientales colombianos, se tomaron y procesaron, mediante técnicas histológicas de rutina, muestras de hígado de los lóbulos derecho e izquierdo, así como de la entrada de la vena porta de cinco toros clínicamente sanos. Las principales lesiones observadas en estos tejidos fueron colangiohepatitis mononuclear, macrófagos espumosos, acumulación moderada de pigmentos biliares, muerte de hepatocitos, hepatocitos binucleados, moderada hiperplasia de ductos biliares y múltiples focos de fibrosis leve en áreas periportales, que fueron corroborados por tinción tricrómica de Masson. Estas lesiones se distribuyeron predominantemente en la entrada de la vena porta y se localizaron con frecuencia en la entrada de la región periportal. Dado que estas lesiones se atribuyen comúnmente al consumo de Brachiaria decumbens, y estaban presentes en animales clínicamente sanos exclusivamente alimentados con esta pastura, se concluye que las lesiones aquí encontradas fueron causadas por la Brachiaria decumbens. Se sugiere ampliar este estudio involucrando más bovinos, granjas y municipios.

[Cerebral venous thrombosis: when etiology makes the difference]. / Trombosis venosa cerebral: cuando la etiología marca la diferencia.

OBJECTIVES: To make a retrospective study of the clinical, etiological, diagnostic and prognostic features of cerebral vein and sinus thrombosis (CVST) diagnosed at our University Hospital. METHODS: We performed a systematic research of the clinical records of our University Hospital's electronic database (1977-2009) using the key words <>. RESULTS: Ninety-five possible cases were found, and 16 were excluded due to alternative or uncertain diagnosis. Seventy-nine patients (43 females), median age of 46 years (2-82), were studied. Hereditary or acquired thrombophilia was detected in 22 patients (27.8%): prothrombin G20210A mutation (10), factor V Leyden (3), protein C deficiency (2), homozygous MTHFR C677T mutation (1), antiphospholipid syndrome (7) and hematological conditions (3). CVST was associated with infection in 17 cases, intracranial neoplasm in 9, malignancy in 13, treatment with prothrombotic drugs in 20 (including substitutive/antineoplastic hormones and oral contraceptives) and other causes in 8. Thirteen cases were idiopathic. Clinical presentation was intracranial hypertension in 83.5%, focal deficits in 45.6% and seizures in 12.6 %. Transverse (57%) and superior sagittal sinus (49.4%) were the most commonly involved. Seizures occurred in 25.3%, venous infarction in 41% and severe intracranial hypertension in 22.8 %. Up to 31.6 % required surgical drainage, decompressive craniectomy or ventricular drainage. Nine cases associated peripheral venous thromboembolism and 4 CVST recurred. Evolution was favorable (modified Rankin scale 0-2 at 3 months) in 74.7%. Mortality rate was 13.9% (11 patients). Neoplastic and infectious origin was significantly associated with mortality and disability. CONCLUSION: We describe a large retrospective series of CVST where infectious and neoplastic etiologies were linked to an unfavorable outcome.

Microsomal and cytosolic biotransformation of aflatoxin B1 in four poultry species.

1. This research evaluated differences in hepatic in vitro metabolism of aflatoxin B1 (AFB1) on selected avian species. 2. Microsomal and cytosolic liver fractions were obtained from chickens, ducks, quails and turkeys; eight males and eight females of each. 3. All microsomes studied produced AFB1-8,9-exo-epoxide (AFBO), a metabolite regarded as the active product of AFB1. Turkey microsomes produced 1.8 and 3.5 times more AFBO than quails and chickens microsomes, respectively. 4. Males from evaluated birds produced more AFBO than females, but statistically-significant differences between genders were observed only in ducks and turkeys. 5. The cytosolic fraction from all four species produced aflatoxicol (AFL). Turkey and duck hepatic cytosol produced more AFL than from quail and chickens. 6. It is known that turkeys are very sensitive to AFB1, quails are intermediate and chickens are particularly resistant; the differences in AFBO production shown in our study may help to explain the difference in vivo responses among turkeys, quail and chickens. 7. Moreover, AFL may be related to AFB1 toxicity; it was produced in larger amounts by hepatic cytosol from the more susceptible species. 8. Because AFBO production by microsomes in ducks was relatively low, it is possible that other toxicity mechanisms are involved in this highly susceptible species.

[Pronostic value of the immunohistochemical expression of cyclin D1 (DCS6) in epidermoid larynx carcinoma]. / Valor pronóstico de la expresión inmunohistoquímica de ciclina D1 en carcinoma epidermoide de laringe.

In this paper we carried out an immunohistochemical study of cyclin D1 (DCS6 ) expression in a series of 195 patients with laryngeal carcinoma that were diagnosticated, treated and followed at the Department of Otolaryngology at "Virgen de la Salud" Hospital (Toledo, Spain) for a time of 5 years. In the cases with lymph node metastasis we also studied cyclin D1 expression at this level. Furthermore we have analysed the value of cyclin D1 expression as a prognostic factor (tumor recurrence, deads due to cancer and survival) and we evaluate the relationship between cyclin D1 expression and other clinic and pathologic parameters.

[Prognostic value of the inmunohïstochemical expression of protein p27KIP1 in laryngeal cancer]. / Valor pronóstico de la expresión inmunohistoquímica de la proteína p27KIP1 en cáncer de laringe.

In this paper we carried out an immunohistochemical study of protein p27KIP1 expression in a series of 195 patients with laryngeal carcinoma that were diagnosticated, treated and followed at the Department of Otolaryngology at "Virgen de la Salud" Hospital (Toledo, Spain). In the cases with lymph node metastasis we also studied p27KIP1 expression at this level. Furthermore we have analysed the value of protein p27KIP1 expression as a prognostic factor (tumor recurrence, deads due to cancer and survival) and we evaluate the relationship between p27KIP1 expression and other clinic and pathologic parameters.

[Prognostic value of the immunohistochemical expresion of protein Rb in epidermoid carcinoma of the larynx]. / Valor pronóstico de la expresión inmunohistoquímica de la proteína Rb en el carcinoma epidermoide de laringe.

In this paper we carried out an immunohistochemical study of protein Rb (G3-245) expression in a series of 195 patients with laryngeal carcinoma that were diagnosticated, treated and followed at the Department of Otolaryngology at "Virgen de la Salud" Hospital (Toledo, Spain) for a time of 5 years. In the cases with lymph node metastasis we also studied Rb expression at this level. Furthermore we have analysed the value of Rb expression as a prognostic factor (tumor recurrence, deads due to cancer and survival) and we evaluate the relationship between Rb expression and other clinic and pathologic parameters.

[Prognosis value of the immunohystochemical expresion of the p21WAF1 in the larynx cancer]. / Valor pronóstico de la expresión inmunohistoquímica de la proteina p21WAF1 en cáncer de laringe.

In this paper we carried out an immunohistochemical study of protein p21WAF1 (EA10) expression in a series of 195 patients with laryngeal carcinoma that were diagnosticated, treated and followed at the Department of Otolaryngology at "Virgen de la Salud" Hospital (Toledo, Spain). In the cases with lymph node metastasis we also studied p21WAF1 expression at this level. Furthermore we have analysed the value of protein p21WAF1 expression as a prognostic factor (tumor recurrence, deads due to cancer and survival) and we evaluate the relationship between p21WAF1 expression and other clinic and pathologic parameters.

[Prognosis value of the immunohistochemical expresion of the bcl-2 in the larynx epidermoid cancer]. / Valor pronóstico de la expresión inmunohistoquímica de la proteina bcl-2 en carcinoma de laringe.

In this paper we carried out an immunohistochemical study of bcl-2 protein expression in a series of 195 patients with laryngeal carcinoma that were diagnosticated, treated and followed at the Department of Otolaryngology at "Virgen de la Salud" Hospital (Toledo, Spain). In the cases with lymphonode metastasis we also analysed bcl-2 protein expression at this level. Furthermore we have studied the value of bcl-2 protein expression as a prognostic factor (tumor recurrence, deads due to cancer and survival) and we analysed the relationship between bcl-2 protein expression and other clinic and pathologic parameters.

[Laryngeal actinomycosis]. / Actinomicosis laríngea.

Actinomycosis is a rare infectious disease in our practice and clinically it is charactherized by the presence of granulomatous lesions of subacute or chronic evolution. Most of the cases of actinomycosis are localised in the cervico-facial area, being the laryngeal one uncommon. We present a clinical case of a 53 years-old male diagnosed of primary laryngeal actinomycosis and we realise a bibliographic revision on this subject emphazising the diagnosis techniques and the differential diagnosis of this kind of lesions.

[Inmunohistochimic expresion of p53 protein and TTS prognostic value in the larynx cancer]. / Expresión inmunohistoquímica de la proteina p53 y su valor pronóstico en el cancer de laringe.

We carried out an immunohistochemical study of p53 (DO7) expression in a series of 195 patients with laryngeal squamous cell carcinoma, treated and followed at the Department of Otolaryngology Virgen de la Salud Hospital (Toledo, Spain). In the cases with lymph node metastasis we also studied p53 expression at this site. We have investigated the value of p53 expression as a prognostic factor (tumor recurrence, deads due tu cancer and survival) and we have evaluated the relationship between p53 expression and other clinicopathologic characteristics.

[Pronostic value of the MDM-2 protein expression in the larynx cancer]. / Valor pronóstico de la expresión de la proteina MDM-2 en cancer de laringe.

In this paper we carried out an immunohistochemical study of Mdm-2 (IF2) expression in a series of 195 patients with laryngeal carcinoma that were diagnosticated, treated and followed at the Department of Otolaryngology at Virgen de la Salud Hospital (Toledo, Spain). In the cases with lymph node metastasis we also studied Mdm-2 expression at this level. We also wanted to investigate the value of Mdm-2 expression as a prognostic factor (tumor recurrence, deads due to cancer and survival) and we have evaluated the relationship between Mdm-2 expression and other clinic and pathologic characteristics.

[A review of sleep disorders in depression]. / Una revisión de las alteraciones del sueño en la depresión.

AIMS: The main aims of this study are, on the one hand, to report on the current state of the art in research into the characteristics of sleep in depression and, on the other hand, to analyse the theoretical and practical implications of these results. METHOD: We review the main findings regarding the sleep disorders linked with depression and offer data about the sensitivity and specificity of these measures. The aetiopathogenic meaning of these sleep disorders is also analysed and finally we present some of the principal theoretical models put forward to explain these data. CONCLUSIONS: A number of studies have observed significant alterations in electroencephalographic patterns during sleep in subjects with depression. Some of the most commonly mentioned findings involve disorders affecting the continuity and duration of sleep, a reduction of phases 3 and 4 of sleep, lowered latency in REM (rapid eye movements) sleep, and a longer and more intense first period of REM. This technique is presently of limited use as a diagnostic tool in depression. The pathophysiological mechanisms governing sleep disorders in depression are not yet known, but sleep studies still play an important role in research into depression, especially in areas concerning the prediction of responses to treatment, the prognosis of relapses, longitudinal results, familial studies and in research into aetiological models

Electrodermal activity during total sleep deprivation and its relationship with other activation and performance measures.

The present study analyses the variations of the skin resistance level (SRL) during 48 h of total sleep deprivation (TSD) and its relationship to body temperature, self-informed sleepiness in the Stanford Sleepiness Scale (SSS), and reaction time (RT). All of the variables were evaluated every 2 h except for the SSS, which was evaluated every hour. A total of 30 healthy subjects (15 men and 15 women) from 18 to 24 years old participated in the experiment. Analyses of variance (ANOVAs) with TSD days and time-of-day as factors showed a substantial increase of SRL, SSS, and RT, and a decrease in body temperature marked by strong circadian oscillations. The interaction between day by time-of-day was only significant for RT. Furthermore, Pearson's correlations showed that the increase of SRL is associated to the decrease in temperature (mean r=-0.511), the increase of SSS (mean r=0.509), and the deterioration of RT (mean r=0.425). The results support previous TSD reports and demonstrate the sensitivity of SRL to TSD. The non-invasive character of SRL, its simplicity, and its relationships with other activation parameters, widely validated by previous literature, convert SRL into an interesting and useful measure in this field.

Homocysteine levels in elderly Spanish people: influence of pyridoxine, vitamin B12 and folic acid intakes.

BACKGROUND: Serum homocysteine levels are a risk factor in cardiovascular disease. Knowledge on how dietary factors might affect these levels is therefore of interest. OBJECTIVE: To evaluate serum homocysteine levels in a group of elderly people and analyse the effect of pyridoxine, vitamin B12 and folic acid intakes on these levels. DESIGN: The study subjects were 130 independently-living elderly people over the age of 65. A dietetic study was performed using a 7-day food record. Serum homocysteine levels were determined by HPLC. RESULTS: Mean pyridoxine, vitamin B12 and folate intakes were 67.2+/-16.8%, 392.8+/-549.2% and 84.5+/-28.3% of recommended values respectively. With regard to sex, differences were seen only for vitamin B12 intake (9.1+/-12.7 microg/day in men, and 6.5+/-8.8 microg/day in women). Some 93.6% of subjects showed pyridoxine intakes below those recommended, as did 17.6% with respect to vitamin B12 and 72.8% with respect to folic acid. Homocysteine levels were 12.4 micromol/l (12.6+/-3.7 micromol/l in men and 12.2+/-7.9 micromol/l in women) (P<0.05). No significant differences were seen in homocysteine levels between subjects with lower than recommended intakes of pyridoxine or vitamin B12 and those with better intakes. However, subjects with folic acid intakes below 200 microg/day showed higher homocysteine levels (13.0+/-6.7 micromol/l) than did subjects with more adequate intakes (10.9+/-4.1 micromol/l) (P<0.05). CONCLUSION: The diet of the study subjects might be improved, especially with respect to pyridoxine and folic acid. Raising the intake of the latter might be especially useful in controlling homocysteine levels and the risk of cardiovascular disease.