Factors associated with workability in Spanish health centre workers.

BACKGROUND: The concept of workability provides a conceptual framework and proposes measures for the evaluation of relevant actions focused on a healthy workforce. In Spain, one of the countries with the highest life expectancy, there are practically no scientific studies on workability and its associated factors. AIMS: The objective of this study is to examine the associations between workability and variables related to health and work in a sample of workers from Spanish health centres. METHODS: Cross-sectional study including 1184 health centre workers who completed a questionnaire at baseline, comprising measures of workability, health and other work-related factors. Workability has been analysed as a one-factor construct, and as a two-factor construct. Multinomial logistic regression models were used to analyse factors associated with workability. RESULTS: As a one-dimensional construct, workability is associated with physical and mental health, number of hours of worked, insomnia, work and family life balance, adequate training, never having had an accident and type of contract. When the two-factor measure was used, sensitivity of findings increased, and it was identified that those participants who were older, lived alone and have more years of service in their profession also show worse workability. CONCLUSIONS: The present study identified factors associated with the workability of health centre workers. The two-factor workability index (WAI) has better psychometric properties and used in combination with the global measure of WAI, identifies important additional aspects, specifically, age and years of professional experience as additional considerations for the intervention.

Genome-wide profiling of non-smoking-related lung cancer cells reveals common RB1 rearrangements associated with histopathologic transformation in EGFR-mutant tumors.

BACKGROUND: The etiology and the molecular basis of lung adenocarcinomas (LuADs) in nonsmokers are currently unknown. Furthermore, the scarcity of available primary cultures continues to hamper our biological understanding of non-smoking-related lung adenocarcinomas (NSK-LuADs). PATIENTS AND METHODS: We established patient-derived cancer cell (PDC) cultures from metastatic NSK-LuADs, including two pairs of matched EGFR-mutant PDCs before and after resistance to tyrosine kinase inhibitors (TKIs), and then performed whole-exome and RNA sequencing to delineate their genomic architecture. For validation, we analyzed independent cohorts of primary LuADs. RESULTS: In addition to known non-smoker-associated alterations (e.g. RET, ALK, EGFR, and ERBB2), we discovered novel fusions and recurrently mutated genes, including ATF7IP, a regulator of gene expression, that was inactivated in 5% of primary LuAD cases. We also found germline mutations at dominant familiar-cancer genes, highlighting the importance of genetic predisposition in the origin of a subset of NSK-LuADs. Furthermore, there was an over-representation of inactivating alterations at RB1, mostly through complex intragenic rearrangements, in treatment-naive EGFR-mutant LuADs. Three EGFR-mutant and one EGFR-wild-type tumors acquired resistance to EGFR-TKIs and chemotherapy, respectively, and histology on re-biopsies revealed the development of small-cell lung cancer/squamous cell carcinoma (SCLC/LuSCC) transformation. These features were consistent with RB1 inactivation and acquired EGFR-T790M mutation or FGFR3-TACC3 fusion in EGFR-mutant tumors. CONCLUSIONS: We found recurrent alterations in LuADs that deserve further exploration. Our work also demonstrates that a subset of NSK-LuADs arises within cancer-predisposition syndromes. The preferential occurrence of RB1 inactivation, via complex rearrangements, found in EGFR-mutant tumors appears to favor SCLC/LuSCC transformation under growth-inhibition pressures. Thus RB1 inactivation may predict the risk of LuAD transformation to a more aggressive type of lung cancer, and may need to be considered as a part of the clinical management of NSK-LuADs patients.

Porcine colonization of the Americas: a 60k SNP story.

The pig, Sus scrofa, is a foreign species to the American continent. Although pigs originally introduced in the Americas should be related to those from the Iberian Peninsula and Canary islands, the phylogeny of current creole pigs that now populate the continent is likely to be very complex. Because of the extreme climates that America harbors, these populations also provide a unique example of a fast evolutionary phenomenon of adaptation. Here, we provide a genome wide study of these issues by genotyping, with a 60k SNP chip, 206 village pigs sampled across 14 countries and 183 pigs from outgroup breeds that are potential founders of the American populations, including wild boar, Iberian, international and Chinese breeds. Results show that American village pigs are primarily of European ancestry, although the observed genetic landscape is that of a complex conglomerate. There was no correlation between genetic and geographical distances, neither continent wide nor when analyzing specific areas. Most populations showed a clear admixed structure where the Iberian pig was not necessarily the main component, illustrating how international breeds, but also Chinese pigs, have contributed to extant genetic composition of American village pigs. We also observe that many genes related to the cardiovascular system show an increased differentiation between altiplano and genetically related pigs living near sea level.

Impact of a multidisciplinary team training programme on rectal cancer outcomes in Spain.

AIM: The Spanish Rectal Cancer Project was established in 2006, inspired by the Norwegian Rectal Cancer Project. It consisted of an educational project aiming to introduce mesorectal excision surgery to surgeons, pathologists and radiologists. Its effect on local recurrence (LR) was compared with the Norwegian Project. METHOD: An observational cohort study was carried out including all patients (4700) with rectal cancer from a population of 19 329 992 inhabitants operated on in 51 Spanish hospitals between March 2006 and June 2010. Curative resection was defined as a resection with an uninvolved circumferential margin in patients without distant metastases and without intra-operative rectal perforation. The effectiveness of the programme was measured by a central registry with feedback to participating institutions of their own results compared with the national average. The main outcome measures were LR and adverse effects in curative resections. RESULTS: Of the 4700 patients, 3213 had a resection considered to be curative. LR rates were 4.7% (95% CI 0.03-0.59), metastasis rate was 16% (95% CI 0.14-0.17) and overall survival was 87.8% (95% CI 0.86-0.89). Multivariate analysis showed that advanced TNM stage and decreasing distance of the tumour from the anal verge had a negative influence on LR. CONCLUSION: This study shows that the results obtained in Norway have been reproduced in a larger population in Spain applying a similar methodology.

[Translated article] Vertebral metastases. En bloc treatment.

En bloc resection of vertebral metastases has been the subject of study in medical literature due to its impact on patients' quality of life and effectiveness in local disease control. This bibliographic analysis examines the findings and perspectives of published studies concerning en bloc resection of oligometastases in the spine. The technique, which involves the complete removal of the tumour along with a portion of the surrounding bone, has been shown to improve local tumour control, reduce recurrence, and potentially prolong patient survival compared to conventional decompression and stabilisation techniques. However, en bloc resection also presents risks and complications, such as surgical morbidity and extended recovery time. Appropriate patient selection, preoperative planning, and a multidisciplinary approach are essential to optimise outcomes. As new techniques and advances in adjuvant treatment develop, en bloc resection of oligometastases in the spine remains an area of interest in oncological research.

Vertebral metastases. En bloc treatment. / Metástasis vertebrales. Tratamiento en bloque.

En bloc resection of vertebral metastases has been the subject of study in medical literature due to its impact on patients' quality of life and effectiveness in local disease control. This bibliographic analysis examines the findings and perspectives of published studies concerning en bloc resection of oligometastases in the spine. The technique, which involves the complete removal of the tumour along with a portion of the surrounding bone, has been shown to improve local tumour control, reduce recurrence, and potentially prolong patient survival compared to conventional decompression and stabilization techniques. However, en bloc resection also presents risks and complications, such as surgical morbidity and extended recovery time. Appropriate patient selection, preoperative planning, and a multidisciplinary approach are essential to optimize outcomes. As new techniques and advances in adjuvant treatment develop, en bloc resection of oligometastases in the spine remains an area of interest in oncological research.

Gender differences, inequalities and biases in the management of Acute Coronary Syndrome.

OBJECTIVE: The approach to Acute Coronary Syndrome from a gender perspective is relatively recent. Research is extensive at epidemiological and clinical levels. However, available evidence, besides neglecting the social dimensions of the disease, has made women invisible. The objective of this review was to analyze the inequalities and gender biases in Acute Coronary Syndrome, from the beginning of the disease process to the final resolution. METHODS: An exhaustive review of the literature of the entire health care process, from risk factors to rehabilitation and recovery, was carried out. The search for articles on gender, gender inequalities, or gender bias was conducted in indexed journals of social and health sciences. Also, a specific search was performed for each stage of the process, such as risk factors, prehospital phase, diagnosis, treatment, and rehabilitation. RESULTS: Results showed the presence of gender biases throughout the entire health care process in Acute Coronary Syndrome. It is shown gender inequalities in the access to medical care, including a poor recognition among women themselves as well as among health professionals; longer prehospital delays; inadequate diagnoses and treatments; or less assistance to cardiac rehabilitation programmes. These biases occurred at the different levels of the health services involved. Finally, this review included recommendations proposed or arising from the revised papers. CONCLUSIONS: Reducing gender biases in Acute Coronary Syndrome implies developing strategies to raise awareness among women, improve training of professionals serving at the different levels of health services, reduce delays, develop health management measures, and promote a research agenda.

Simplified risk-prediction for benchmarking and quality improvement in emergency general surgery. Prospective, multicenter, observational cohort study.

BACKGROUND AND AIMS: Emergency General Surgery (EGS) conditions account for millions of deaths worldwide, yet it is practiced without benchmarking-based quality improvement programs. The aim of this observational, prospective, multicenter, nationwide study was to determine the best benchmark cutoff points in EGS, as a reference to guide improvement measures. METHODS: Over a 6-month period, 38 centers (5% of all public hospitals) attending EGS patients on a 24-h, 7-days a week basis, enrolled consecutive patients requiring an emergent/urgent surgical procedure. Patients were stratified into cohorts of low (i.e., expected morbidity risk <33%), middle and high risk using the novel m-LUCENTUM calculator. RESULTS: A total of 7258 patients were included; age (mean ± SD) was 51.1 ± 21.5 years, 43.2% were female. Benchmark cutoffs in the low-risk cohort (5639 patients, 77.7% of total) were: use of laparoscopy ≥40.9%, length of hospital stays ≤3 days, any complication within 30 days ≤ 17.7%, and 30-day mortality ≤1.1%. The variables with the greatest impact were septicemia on length of hospital stay (21 days; adjusted beta coefficient 16.8; 95% CI: 15.3 to 18.3; P < .001), and respiratory failure on mortality (risk-adjusted population attributable fraction 44.6%, 95% CI 29.6 to 59.6, P < .001). Use of laparoscopy (odds ratio 0.764, 95% CI 0.678 to 0.861; P < .001), and intraoperative blood loss (101-500 mL: odds ratio 2.699, 95% CI 2.152 to 3.380; P < .001; and 500-1000 mL: odds ratio 2.875, 95% CI 1.403 to 5.858; P = .013) were associated with increased morbidity. CONCLUSIONS: This study offers, for the first time, clinically-based benchmark values in EGS and identifies measures for improvement.

Partial short-read sequencing of a highly inbred Iberian pig and genomics inference thereof.

Despite dramatic reduction in sequencing costs with the advent of next generation sequencing technologies, obtaining a complete mammalian genome sequence at sufficient depth is still costly. An alternative is partial sequencing. Here, we have sequenced a reduced representation library of an Iberian sow from the Guadyerbas strain, a highly inbred strain that has been used in numerous QTL studies because of its extreme phenotypic characteristics. Using the Illumina Genome Analyzer II (San Diego, CA, USA), we resequenced ∼ 1% of the genome with average 4 × depth, identifying 68,778 polymorphisms. Of these, 55,457 were putative fixed differences with respect to the assembly, based on the genome of a Duroc pig, and 13,321 were heterozygous positions within Guadyerbas. Despite being highly inbred, the estimate of heterozygosity within Guadyerbas was ∼ 0.78 kb(-1) in autosomes, after correcting for low depth. Nucleotide variability was consistently higher at the telomeric regions than on the rest of the chromosome, likely a result of increased recombination rates. Further, variability was 50% lower in the X-chromosome than in autosomes, which may be explained by a recent bottleneck or by selection. We divided the whole genome in 500 kb windows and we analyzed overrepresented gene ontology terms in regions of low and high variability. Multi organism process, pigmentation and cell killing were overrepresented in high variability regions and metabolic process ontology, within low variability regions. Further, a genome wide Hudson-Kreitman-Aguadé test was carried out per window; overall, variability was in agreement with neutral expectations.

Microcephaly epidemic in Brazil: An earlier chapter.

OBJECTIVE: Identify risk factors for microcephaly and evaluate historical trends of microcephaly and arboviruses to recognize patterns and anomalies that indicate the beginning of the microcephaly epidemic associated with Zika infection. METHODS: The head circumferences of 62,298 newborns was analyzed to identify cases of microcephaly between 2014 and 2017. We compared the groups of newborns with normal head circumferences and those with microcephaly to identify risk factors. A time series with the incidences of microcephaly was analyzed to assess the appearance of anomalous values in order to identify the beginning of the microcephaly epidemic. Data on the incidence of dengue fever was used to develop a control chart, aiming to identify changes in incidence and seasonality that could suggest the circulation of a new arbovirus. FINDINGS: Premature newborns, children of mothers under 20 years of age and those born in 2014 and 2015 had a higher risk of microcephaly. Three quarters with anomalous incidences of microcephaly were identified, the first in 2014 and the others in 2015. The dengue fever epidemic curve in 2013 shows persistence of high incidences in atypical periods, suggesting the entry of a new virus in the 3rd and 4th quarters. CONCLUSIONS: These findings represent epidemiological evidence of the existence of cases of Zika virus between the 2nd quarter of 2013 and the beginning of 2014. The results add new elements to understanding the Zika virus epidemic in the Americas.

NADPH oxidase 4 (Nox4) deletion accelerates liver regeneration in mice.

Liver is a unique organ in displaying a reparative and regenerative response after acute/chronic damage or partial hepatectomy, when all the cell types must proliferate to re-establish the liver mass. The NADPH oxidase NOX4 mediates Transforming Growth Factor-beta (TGF-ß) actions, including apoptosis in hepatocytes and activation of stellate cells to myofibroblasts. Aim of this work was to analyze the impact of NOX4 in liver regeneration by using two mouse models where Nox4 was deleted: 1) general deletion of Nox4 (NOX4-/-) and 2) hepatocyte-specific deletion of Nox4 (NOX4hepKO). Liver regeneration was analyzed after 2/3 partial hepatectomy (PH). Results indicated an earlier recovery of the liver-to-body weight ratio in both NOX4-/- and NOX4hepKO mice and an increased survival, when compared to corresponding WT mice. The regenerative hepatocellular fat accumulation and the parenchyma organization recovered faster in NOX4 deleted livers. Hepatocyte proliferation, analyzed by Ki67 and phospho-Histone3 immunohistochemistry, was accelerated and increased in NOX4 deleted mice, coincident with an earlier and increased Myc expression. Primary hepatocytes isolated from NOX4 deleted mice showed higher proliferative capacity and increased expression of Myc and different cyclins in response to serum. Transcriptomic analysis through RNA-seq revealed significant changes after PH in NOX4-/- mice and support a relevant role for Myc in a node of regulation of proliferation-related genes. Interestingly, RNA-seq also revealed changes in the expression of genes related to activation of the TGF-ß pathway. In fact, levels of active TGF-ß1, phosphorylation of Smads and levels of its target p21 were lower at 24 h in NOX4 deleted mice. Nox4 did not appear to be essential for the termination of liver regeneration in vivo, neither for the in vitro hepatocyte response to TGF-ß1 in terms of growth inhibition, which suggest its potential as therapeutic target to improve liver regeneration, without adverse effects.

Use of tocilizumab in systemic sclerosis: A brief literature review. / Utilización de tocilizumab en la esclerosis sistémica: breve revisión de la literatura.

The available treatments for systemic sclerosis (SS) have limited effectiveness. Treatment with tocilizumab (TCZ), a biological drug that inhibits interleukin 6 (IL-6), has recently been proposed. In this study, we conducted a literature review to assess the safety and efficacy of TCZ in SS. We found 52 articles, 10 of which we selected after evaluating the articles. In a randomised clinical trial, TCZ showed a nonsignificant improvement in the degree of skin induration, while another observational study showed neutral results. In this same clinical trial, the functional respiratory parameters showed a certain degree of stabilization. The safety profile of TCZ is acceptable; however, the current evidence regarding treatment of SS with TCZ is highly limited, although the drug could have a beneficial effect in skin disorder. New clinical trials are needed to determine the usefulness of TCZ in SS.

Subclinical cardiovascular disease and Systemic Sclerosis: A comparison between risk charts, quantification of coronary calcium and carotid ultrasonography.

BACKGROUND AND OBJECTIVES: Recently published population-based cohort studies have shown a high prevalence of cardiovascular disease in Systemic Sclerosis (SSc) patients. The aim of this study is to compare three different methods to measure cardiovascular risk in patients with scleroderma. METHODS: Forty-three SSc patients were included. A prospective study was performed for evaluation of cardiovascular risk and subclinical atheromatosis using 3 non-invasive methods: cardiovascular risk tables, carotid Doppler ultrasonography and quantification of coronary calcium by computerized tomography (CT). RESULTS: The cardiovascular risk charts for the Spanish population did not identify patients at high cardiovascular risk. Framingham-REGICOR identified 13 intermediate-risk patients. Twenty-two patients (51.2%) had plaques on carotid ultrasonography. We performed a ROC curve to identify the best cutoff point for the quantification of coronary artery calcium (CACscore), the value of CACscore > 28 AU (Agatston Units) had the highest sensitivity (73%) and specificity (81%) for the diagnosis of subclinical atheromatosis. In the multiple regression study, age and decreased HDL cholesterol levels were identified as independent factors for subclinical atherosclerotic disease. No disease-related factors were associated with increased subclinical arteriosclerosis. CONCLUSION: Carotid ultrasound and CACscore are useful for identifying subclinical atheromatosis in patients with SSc and are superior compared to risk charts used for general population. HDL cholesterol and age were independent factors for the presence of subclinical atherosclerotic disease. A carotid ultrasound or CT should be performed for early detection of subclinical atheromatosis if these factors are present.

Nasopharyngeal carcinoma: 30-year experience of a single institution in a non-endemic area.

PURPOSE: Over the past years, radiotherapy techniques have changed significantly. The impact of these changes in the management of nasopharyngeal carcinoma (NPC) has not been fully evaluated. METHODS/PATIENTS: Between 1984 and 2014, 223 NPC were diagnosed in our hospital. Prior to 2000, patients were treated with 2D treatment plan (RT2D) that evolved to 3D schemes thereafter (RT3D). RESULTS: Tumors in the RT3D period showed significantly lower stages than those in the RT2D period. 5-year cause-specific survival improved from 55.7% (95% CI: 46.7-64.7%) in the RT2D period to 78.7% (95% CI: 68.7-88.7%) in the RT3D period (P = 0.006). This difference was greater for non-keratinizing NPC, where specific survival went from 63.2% (95% CI: 52.2-74.2%) to 84.4% (95% CI: 74.4-94.4%) (P = 0.014). CONCLUSION: Recent changes in treatment strategies including concurrent chemoradiation and 3D radiotherapy may have impacted in better survival for NPC. Improved imaging techniques may have contributed by earlier detection and better treatment planning.

Primary pleomorphic liposarcoma of the spine. Case report and review of the literature.

INTRODUCTION: To describe a single case, the fourth ever reported, of pleomorphic liposarcoma of the spine and to undertake a review of the literature. PRESENTATION OF CASE: A 60 year old male patient had a bilateral lumbosciatica over a 3 month period. Imaging tests revealed a tumor mass in L1-L3 and a fracture in L2. Also, he had a mural thrombus both in the inferior vena cava and the left renal vein. The biopsy revealed a well-differentiated liposarcoma. En bloc resection of the lesion and stabilization was carried out. Due to the condition of the patient (hemodynamic instability, wound dehiscence and infection, and hypoproteinemia), a decision was made not to subject the patient to either radiation therapy or chemotherapy. The patient was subsequently found to suffer from myopathic paraparesis and a surgical wound infection. At three months, liver metastases were evident, as well as a recurrence of the lesion. A venous thrombosis that extended from the lower iliac vein to the right atrium was observed. The patient died from type I hepatorenal syndrome. DISCUSSION: Pleomorphic liposarcoma of the spine is a rare occurrence. En bloc resection with wide margins is the treatment of choice. The use of radiotherapy in the spine is controversial. The role that should be played by chemotherapy is still unclear, although it has been employed in treatments. CONCLUSION: In spite of treatment, these tumors lead to a poor prognosis, with high rates of recurrence, metastasis, and mortality.

[Factors associated with prehospital delay in men and women with acute coronary syndrome]. / Factores asociados a la demora prehospitalaria en hombresy mujeres con síndrome coronario agudo.

OBJECTIVE: To identify factors associated with prehospital delay in people who have had an acute coronary syndrome. METHODS: Using a survey we studied patients admitted due to acute coronary syndrome in the 33 Andalusian public hospitals, obtaining information about different types of variables: socio-demographic, contextual,clinical, perception, action, and transportation.Multivariate logistic regression models were applied to calculate the odds ratios for the delay. RESULTS: Of the 1,416 patients studied, more than half had a delay of more than an hour. This is associated to distance to the hospital and means of transport: when the event occurs in the same city,using the patient's own means of transport increases the delay, odds ratio = 1.51 (1.02 to 2.23); if the distance is 1 to 25 kilometers from the hospital,there is no difference between the patient's own means of transport and an ambulance, odds ratio =1.41 and odds ratio =1.43 respectively; and when the distance exceeds 25 kilometers transport by ambulance means more delay, odds ratio = 3.13 and odds ratio = 2.20 respectively. Also, typical symptoms reduce delay amongst men but increase amongst women. Also, not caring and waiting for the resolution of symptoms, seeking health care other than a hospital or emergency services, previous clinical history, being away from home, and having an income under 1,500 euros, all increase delay. Respiratory symptoms reduce delay. CONCLUSIONS: Prehospital delay times do not meet health recommendations. The physical and social environment,in addition to clinical, perceptual and attitudinal factors, are associated with this delay.

Bromocriptine and postpartum cerebral angiopathy: a causal relationship?

We describe a postpartum 30-year-old woman who developed headaches, hypertension, and speech disturbances after bromocriptine treatment to suppress lactation. Brain MRI revealed intraparenchymal hematomas, and an angiographic study showed multiple arterial segmental narrowings compatible with postpartum cerebral angiopathy. We also comment on other cases of postpartum cerebral angiopathy.

Cerebral microembolism in acute spontaneous internal carotid artery dissection.

The rate and risk factors for early ischemic recurrence in patients with internal carotid artery dissection (ICAD) are largely unknown. Serial transcranial Doppler (TCD) monitoring of microembolic signals (MES) was performed in 28 consecutive patients with acute ICAD. MES were identified in 13 patients, and early ischemic recurrence occurred in 7. Six of 13 patients with MES and 1 of 15 without MES experienced early ischemic recurrence (p = 0.029). MES detection on serial TCD monitoring may be associated with an increased risk of early ischemic recurrence in patients with acute ICAD.