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Abstract Background The value of abdominal echography in primary care is great because it is innocuous, inexpensive, easy to perform and provides a great deal of information making this the first examination to be requested in cases of probable abdominal disease. However, too many abdominal echographies are probably requested overcrowding the Departments of Radiodiagnosis with not always justified petitions or with repetition of tests based on little clinical criteria. Methods/Design The aim of the study is to evaluate the adequacy and quality of abdominal echographies requested by primary care physicians in the Maresme County (North of Barcelona), develop guidelines for indicating echographies and reevaluate this adequacy after implementing these guidelines. We will perform a two-phase study: the first descriptive, and retrospective evaluating the adequacy and quality of petitions for abdominal echographies, and in the second phase we will evaluate the impact of recommendations for indicating abdominal echographies for PC physicians on the adequacy and quality of echography petitions thereafter. This study will be carried out in 10 primary care centres in the Maresme (Barcelona). 1067 abdominal echographies requested by primary care physicians from the above mentioned centres from January 2007 to April 2010 and referred to the Department of Radiology and the same number of applications after the intervention. All the petitions for abdominal echographies requested will be analysed and the clinical histories will be obtained to determine demographic variables, the reason for the visit and for the echography petition and diagnostic orientation, clinical and echographic data, evaluation of the echographies according to the quality and variables characterising the professionals requesting the echographies including: age, sex, laboral situation, length of time in work post, formation, etc. To achieve a consensus of the adequacy of abdominal echography, a work group including gastroenterologists, radiologists and general practitioners will be created following the nominal group. This will allow the design of guidelines for the indication of abdominal echography and posterior evaluation of their impact among physicians by diffusion and posterior reevaluation of the adequacy of the petitions.

Abstract Background Non alcoholic fatty liver disease (NAFL) consists in the accumulation of fat vacuoles in the cytoplasm of hepatocytes. Many etiologic factors are associated with NAFL, such as, the metabolic syndrome factors, medications, bariatric surgery, nutritional disorders. However, very little information is available on the clinical relevance of this disorder as a health problem in the general population. Methods and design The aim of the study is establish the risk factors most frequently associated with NAFL in a general adult population assigned to the primary care units and to investigate the relationship between each component of the metabolic syndrome and the risk of having a NAFL. A population based case-control, observational and multicenter study will be carried out in 18 primary care units from the "Area de Gestión del Barcelonés Nord y Maresme" (Barcelona) attending a population of 360,000 inhabitants and will include 326 cases and 370 controls. Cases are defined as all subjects fulfilling the inclusion criteria and with evidence of fatty liver in an abdominal ultrasonography performed for any reason. One control will be randomly selected for each case from the population, matched for age, gender and primary care center. Controls with fatty liver or other liver diseases will be excluded. All cases and controls will be asked about previous hepatic diseases, consumption of alcohol, smoking and drugs, and a physical examination, biochemical analyses including liver function tests, the different components of the metabolic syndrome and the HAIR score will also be performed. Paired controls will also undergo an abdominal ultrasonography. Discussion This study will attempt to determine the factors most frequently associated with the presence of NAFL investigate the relationship between the metabolic syndrome and the risk of fatty liver and study the influence of the different primary care professionals in avoiding the evolution of the disease.

Abstract Background Fatty liver disease is characterized by the accumulation of fat vacuoles inside of the hepatocytes. Non alcoholic fatty liver is associated with obesity, type 2 diabetes, dyslipemia, the intake of certain drugs and with the so-called metabolic syndrome. However, there is little information on the clinical relevance of this disorder as a healthcare problem in the general population, since the studies published generally include a limited number of patients and the diagnosis is established on the basis of clear biochemical alterations and liver biopsy. Methods/Design The aim of the study is the prevalence of non-alcoholic fatty liver disease in a general adult population by hepatic ultrasonography. A population-based, descriptive, transversal, multicentre study. Eighteen primary care centres of the north of Barcelona and the Maresme Areas of Healthcare Management attending an urban and semi-urban population of 360.000 inhabitants. A randomized sample of 786 subjects of 15 years or older were selected from the population and assigned to the participating centres according to the Primary Care Information System (SIAP): This population is practically the same as the general population of the area. The following determinations will be carried out in all the participants: hepatic ultrasonography to detect fatty liver, a questionnaire concerning liver diseases, alcohol intake, smoking and drug use, physical examination including abdominal perimeter and body mass index and biochemical analysis including liver function tests and parameters related to the metabolic syndrome and the HAIR score. Ultrasonographic diagnosis of fatty liver will be made according to established criteria (American Gastroenterology Association) and diagnosis of metabolic syndrome according to the criteria of the European Group for the Study of Insulin Resistance. Discussion This study will attempt to determine the prevalence of non alcoholic fatty liver disease, as well as, the factors most frequently associated with the presence of this disease to thereby achieve the most appropriate treatment and avoid the evolution of the disease.

Background: Venous thromboembolism (VTE) and major bleeding (MB) are common in cancer patients. Reduced-doses of antithrombotics as secondary prophylaxis have limited data. This work aims to describe and to compare treatments and outcomes for cancer-associated VTE., Research Design and Methods: Retrospective study. Adults with cancer-associated VTE were included. After 3-6 months of full-doses of anticoagulants, three strategies were considered: A) lowering the doses; B) maintaining full-doses; C) stopping treatment. The strategy and medication used were shown in a descriptive analysis and the rate of bleeding and VTE-recurrence between those in a comparative analysis., Results: A total of 420 patients were included, 56.2% received DOACs, 43.8% enoxaparin. Strategy was defined in 257 patients: A (50.2%), B (46.3%), and C (3.5%). Forty-one (9.8%) had VTE-recurrence and 15 (3.6%) had MB or clinically relevant non-major bleeding (CRNMB).According to strategy, recurrent-VTE was 8.5% (A), 4.2% (B), and 11.1 (C) ( p  = 0.22), MB or CRNMB was 0.8% (A), 1.7% (B), and 0% (C) ( p  = 0.64)., Conclusions: DOACs and strategy A were the most frequently used agent and strategy, respectively. There were no differences between medications or strategies used. The results must be interpreted with caution, and it is a retrospective single-center study, probably with information and selection bias.

Background and Objective: The determination of pharmacokinetic properties of new chemical entities is a key step in the process of drug development. Positron emission tomography (PET) is an ideal technique to obtain both biodistribution and pharmacokinetic parameters of new compounds over a wide range of chemical modalities. Here, we use a multi-radionuclide/multi-position labelling approach to investigate distribution, elimination, and metabolism of a triazole-based FKBP12 ligand (AHK2) with potential application in neuromuscular disorders., Methods: Target engagement and stabilizing capacity of the drug candidate (AHK2) towards FKBP12-RyR was evaluated using competitive ligand binding and proximity ligation assays, respectively. Subsequently, AHK2 was labelled either with the positron emitter carbon-11 ( 11 C) via 11 C-methylation to yield both [ 11 C]AHK2.1 and [ 11 C]AHK2.2, or by palladium-catalysed reduction of the corresponding 5-iodotriazole derivative using 3 H gas to yield [ 3 H]AHK2. Metabolism was first investigated in vitro using liver microsomes. PET imaging studies in rats after intravenous (IV) administration at different doses (1 µg/Kg and 5 mg/Kg) were combined with determination of arterial blood time-activity curves (TACs) and analysis of plasma samples by high performance liquid chromatography (HPLC) to quantify radioactive metabolites. Arterial TACs were obtained in continuous mode by using an in-house developed system that enables extracorporeal blood circulation and continuous measurement of radioactivity in the blood. Pharmacokinetic parameters were determined by non-compartmental modelling of the TACs., Results: In vitro studies indicate that AHK2 binds to FKBP12 at the rapamycin-binding pocket, presenting activity as a FKBP12/RyR stabilizer. [ 11 C]AHK2.1, [ 11 C]AHK2.2 and [ 3 H]AHK2 could be obtained in overall non-decay corrected radiochemical yields of 14 ± 2%, 15 ± 2% and 0.05%, respectively. Molar activities were 60-110 GBq/µmol, 68-122 GBq/µmol and 0.4-0.5 GBq/μmol, respectively. In vitro results showed that oxidation of the thioether group into sulfoxide, demethylation of the CH 3 O-Ar residue and demethylation of -N(CH 3 ) 2 were the main metabolic pathways. Fast metabolism was observed in vivo. Pharmacokinetic parameters obtained from metabolite-corrected arterial blood TACs showed a short half-life (12.6 ± 3.3 min). Dynamic PET imaging showed elimination via urine when [ 11 C]AHK2.2 was administered, probably reflecting the biodistribution of [ 11 C]methanol as the major metabolite. Contrarily, accumulation in the gastrointestinal track was observed after administration of [ 11 C]AKH2.1., Conclusions: AHK2 binds to FKBP12 at the rapamycin-binding pocket, presenting activity as a FKBP12/RyR stabilizer. Studies performed with the 3 H- and 11 C-labelled FKBP12/RyR stabilizer AHK2 confirm fast blood clearance, linear pharmacokinetics and rapid metabolism involving oxidation of the sulfide and amine moieties and oxidative demethylation of the CH 3 -O-Ar and tertiary amine groups as the main pathways. PET studies suggest that knowledge about metabolic pathways is paramount to interpret images.

Introduction: The objective of this study was to compare the numeric cut-off index (COI) of automated antigen tests with the cycle-threshold (Ct) value., Materials and Methods: COI values of all samples processed with the Elecsys® SARS-CoV-2 Antigen (Roche, Switzerland) from January to February 2022 were retrieved and the positive were compared to RdRP Cts of Allplex Variants I (Seegene, Korea). COI between 0.6 and 1 were considered indeterminate and overproved by RT-PCR., Results: From 13,937 samples 7944(57%) were positive and 189(1.35%) indeterminate. There was a strong correlation between Cts and COI values at the positive samples, but that was not the case for indeterminates., Conclusions: COI values of the positive samples (COI >1) are comparable to Ct values and may therefore be used as proxy viral loads, however this is not the case for indeterminate samples., Competing Interests: Declaration of competing interest The authors report no conflicts of interest relevant to this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

From the very beginning of the SARS-CoV-2 pandemic, one of the very few common opinions was that to control the expansion of the virus as many as the possible test had to be done. Antigen tests, being affordable and easy and fast to use, represented a great opportunity to expand the testing capacities of many healthcare systems. However, in 2021 with the appearance of the new SARS-CoV-2 variants, variant tracking strategies had to be implemented, which often included needing a second test to determine the variant of the patients diagnosed with antigen tests or not taking these samples into consideration at all. Therefore, we proposed recovering the positive antigen test devices to include them in our routine variant tracking strategy. The recovered positive antigen test devices obtained from 1st April 2021 to 15the January 2022 were analysed following the variant tracking protocol in force. The results obtained were compared to the positive samples detected by RT-PCR which were processed for variant tracking during the same period. 21,304 samples were processed, 6297 from the recovered positive antigen devices and 15,007 from the standard nasopharyngeal swabs. Only 773 (3.63%) samples were no conclusive, 104 (1.65%) from the recovered antigen devices and 669 (4.46%) from the RT-PCR positive group. This difference was statistically significant (p < 0.01). Taking this into account the proposed method is suitable and very recommendable, as it is an important measure to have a better and immediate picture of the circulating variants in every community., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Glomangiomyomatosis is an extremely rare variant of glomus tumours. We describe the first known case of paravertebral glomangiomyomatosis in the literature to cause spinal cord compression. A 45-year old female patient presented with sudden onset of left leg pain and progressive weakness in left-sided hip flexion. An MRI spine revealed a large, lobulated, heterogeneous mass cantered on the left L2/3 foramen, mimicking a dumbbell nerve sheath tumour. The mass was invading the psoas muscle and displayed evidence of recent haemorrhage. The patient underwent debulking of the lesion via a left retroperitoneal approach. Surgery was uneventful, with clinical improvement and resolution of leg pain post-operatively. Histopathology of the tumour revealed delineated glomus-like cells and foci of spindled shaped cells resembling myoid differentiation. Immuno-histochemical features of the tumour confirmed the diagnosis of glomangiomyomatosis. The patient continued under close follow up, representing 18 months later with clinical and radiological progression of the disease with similar symptoms of leg pain but no weakness. Follow up MRI revealed progression of the intraspinal and paraspinal components of the tumour with thecal compression. A posterior approach was utilized in order to decompress the intraspinal component, which again was uneventful, and improved the patient's symptoms. This is the first known case of paravertebral glomangiomyomatosis in the literature and this rare entity should be considered in the differential diagnosis of nerve sheath tumours due to risk of progression and recurrence.

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare cancer-predisposition syndrome associated with a high risk of developing a spectrum of malignancies in childhood and adolescence, including brain tumours. In this report, we present the case of an 8-year-old boy with acute headache, vomiting and an episode of unconsciousness in whom brain imaging revealed a high-grade glioma (HGG). The possibility of an underlying diagnosis of CMMRD was suspected radiologically on the basis of additional neuroimaging findings, specifically the presence of multiple supratentorial and infratentorial developmental venous anomalies (DVAs) and malformations of cortical development (MCD), namely, heterotopic grey matter. The tumour was debulked and confirmed to be a HGG on histopathology. The suspected diagnosis of CMMRD was confirmed on immunohistochemistry and genetic testing which revealed mutations in PMS2 and MSH6. The combination of a HGG, multiple DVAs and MCD in a paediatric or young adult patient should prompt the neuroradiologist to suggest an underlying diagnosis of CMMRD. A diagnosis of CMMRD has an important treatment and surveillance implications not only for the child but also the family in terms of genetic counselling.

Background: Herpes simplex virus type 2 (HSV-2) is the most common cause of genital herpes (GH), but genital infection by herpes simplex virus type 1 (HSV-1) is increasing. The aim of this study was to analyze and compare epidemiological characteristics of patients with GH., Methods: Retrospective study conducted from January 2004 to December 2015 in patients with GH attended at two Sexually Transmitted Diseases (STDs) medical consultation of Bilbao-Basurto Integrated Health Organisation in Northern Spain. Patient's medical history was reviewed and data of interest was analyzed., Results: One thousand three patients (524 male and 479 female) were reviewed. HSV-2 was detected in 74%. The proportion of HSV-1 increased during the study period, significantly in men (28% in 2004-2007 vs. 50% in 2012-2015). More female than male had HSV-1 infection (56% vs. 44%). The proportion of primary infection was higher among HSV-1 compared to HSV-2 (79% vs. 21%). Among the patients with HSV-1, primary infection was higher among men (86%) and in younger than 30 years. Recurrent GH was higher among HSV-2 infections (63%). In a multivariate model older age, geographic origin outside Spain, recurrent infection, prior contact with a partner's genital herpetic lesions, previous N. gonorrhoeae infection and prostitution were significantly associated with HSV-2 infection., Conclusions: HSV-2 was the most common causative agent of GH, but the proportion of HSV-1 increased. Overall, antecedent of STD and sexual risk behaviors were more frequent in patients with genital HSV-2 infection., (Copyright © 2020 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

In this study, we report three paediatric cases of Diffuse Glioneuronal Tumours with Oligodendroglioma-like features and Nuclear Clusters (DGONC)., (© 2020 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)

The hypothesis of rescuing FKBP12/RyR1 interaction and intracellular calcium homeostasis through molecular "reshaping" of FKBP12 was investigated. To this end, novel 4-arylthioalkyl-1-carboxyalkyl-1,2,3-triazoles were designed and synthesized, and their efficacy was tested in human myotubes. A library of 17 compounds (10a-n) designed to dock the FKBP12/RyR1 hot-spot interface contact residues, was readily prepared from free α-amino acids and arylthioalkynes using CuAAC "click" protocols amenable to one-pot transformations in high overall yields and total configurational integrity. To model nitro-oxidative stress, human myotubes were treated with the peroxynitrite donor SIN1, and evidence was found that some triazoles 10 were able to normalize calcium levels, as well as FKBP12/RyR1 interaction. For example, compound 10 b at 150 nM rescued 46% of FKBP12/RyR1 interaction and up to 70% of resting cytosolic calcium levels in human myotubes under nitro-oxidative stress. All compounds 10 analyzed showed target engagement to FKBP12 and low levels of cytotoxicity in vitro. Compounds 10b, 10c, 10h, and 10iR were identified as potential therapeutic candidates to protect myotubes in muscle disorders with underlying nitro-oxidative stress, FKBP12/RyR1 dysfunction and calcium dysregulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Introduction: Unicameral bone cysts (UBC), also known as simple bone cysts, are common benign bone lesions filled with fluid, primarily occurring in children and adolescents. Although they can develop in any bone, UBCs usually affect the long bones. Materials & Methods: A 53 year old male patient was found incidentally to have a calvarian lesion in the parietal region overlying the superior sagittal sinus (SSS) (Figure 1). The differential diagnosis included a large arachnoid granulation, haemangioma of bone, a giant cell tumour or tuberculous infection. The patient was planned for elective surgery to remove the lesion and establish the diagnosis. Surgery was uneventful. Conclusion: To the best of our knowledge we describe the first case of UBC affecting the cranial vault. The patient underwent surgery.

The implementation of an Electronic Medical Record (EMR) in the public healthcare system of Buenos Aires City began in June 2016. AGISE is a government department that assists in health decision-making processes by providing timely and quality data. In this study we designed a professional development program to improve organizational capacities for health analytics.

Sylvian fissure meningiomas (SFMs) represent a rare subgroup of nondural-based tumors arising from the meningothelial cells within the arachnoid of the Sylvian fissure. SFMs are more frequent in young males, usually manifest with seizures and display the same radiological features of meningiomas in other locations. Although the absence of dural attachment makes these tumors suitable for a complete resection, their anatomical relationships with the middle cerebral artery branches have impaired its achievement in half of them. To the best of our knowledge, only five atypical WHO grade II SFMs have been previously described. We provide a literature review of SFMs WHO grades I-II and discuss common characteristics and surgical challenges we found in a similar case.

To improve the selectivity of magnetic nanoparticles for tumor treatment by hyperthermia, Fe 3 O 4 nanoparticles have been functionalized with a peptide of the type arginine-glycine-aspartate (RGD) following a "click" chemistry approach. The RGD peptide was linked onto the previously coated nanoparticles in order to target α v β 3 integrin receptors over-expressed in angiogenic cancer cells. Different coatings have been analyzed to enhance the biocompatibility of magnetic nanoparticles. Monodispersed and homogeneous magnetite nanoparticles have been synthesized by the seed growth method and have been characterized using X-ray diffraction, thermogravimetric analysis, infrared spectroscopy, transmission electron microscopy and magnetic measurements. The magnetic hyperthermia efficiency of the nanoparticles has also been investigated and cytotoxicity assays have been perfomed for functionalized nanoparticles., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Primary involvement of the spinal cord by non-Hodgkin lymphoma is exceptionally rare. We report one such case in a 46-year-old gentleman which was successfully treated with surgery and adjuvant chemotherapy.

In recent years, new indications have been suggested for 5-ALA, particularly for cystic lesions. We report the use of 5-ALA fluorescence in an intraparenchymal supratentorial endodermal cyst of a 52-year-old female presenting with headache, progressive right side hemiparesis and anomic aphasia. She underwent an image-guided 5-ALA-assisted left minicraniotomy for fenestration of the cystic lesion into the ventricular system. The capsule of the cyst was noted to fluoresce with 5-ALA. She recovered from the previous deficits and the cyst decreased in size. To the best of our knowledge, this is the first time 5-ALA fluorescence is reported in a case of endodermal cyst.

Enterogenous cysts (ECs) are endodermal lesions resulting from splitting anomalies in the neuroenteric canal. We report the case of a 64-year-old patient who presented with a sudden headache followed by collapse. Brain computed tomography revealed a hyperdense lesion in the anterior part of the third ventricle with obstructive hydrocephalus. A presumptive diagnosis of colloid cyst was made and he underwent a right transcortical approach for lesion resection. The histopathological examination revealed an EC. ECs are common lesions in the cervical-thoracic spine but rare in the supratentorial compartment with only two previously described cases occurring in the third ventricle.

Introduction: The prognostic value of seizures in patients with glioblastoma is currently under discussion. The objective of this research was to study the risk factors associated with seizures occurring at the diagnosis of glioblastoma and the role of seizures as a predictive factor for survival., Material and Methods: We prospectively analyzed the clinical data over the course of the disease, baseline MR imaging, and histological characteristics (p53 overexpression, the Ki67 proliferation index, and presence of the IDH1 R132H mutation), in glioblastomas treated in a single hospital from November 2012 to July 2014. The study follow-up cutoff point was October 2015., Results: In total, 56 patients were recruited (57% men, mean age 57 years). Median baseline score on the Karnofsky performance scale was 80. Complete tumor debulking followed by radiochemotherapy was achieved in 58.9%. Mean survival was 13.6 months. Epileptic seizures were the presenting symptom in 26.6% of patients, and 44.6% experienced seizures at some point during the course of the disease. On multivariate analysis, the single factor predicting shorter survival was age older than 60 years (hazard ratio 3.565 (95%CI, 1.491-8.522), p=0.004). Seizures were associated with longer survival only in patients younger than 60 years (p=0.035). Younger age, the IDH1 R132H mutation, and p53 overexpression (>40%) were related to seizures at presentation. Baseline MRI findings, including tumor size, and the Ki67 proliferation index were not associated with the risk of epileptic seizures or with survival. Prophylactic antiepileptic drugs did not increase survival time., Conclusions: Seizures as the presenting symptom of glioblastoma predicted longer survival in adults younger than 60 years. The IDH1 R132H mutation and p53 overexpression (>40%) were associated with seizures at presentation. Seizures showed no relationship with the tumor size or proliferation parameters., (Copyright © 2016 Elsevier B.V. All rights reserved.)