Treatment and Diagnostic Approach for Lhermitte-Duclos Disease and Suspected Cowden Syndrome.

Lhermitte-Duclos disease (LDD) is a rare entity, which may or may not be associated with Cowden syndrome (CS). The authors present a 26-year-old male with a history of emergency treatment due to acute obstructive hydrocephalus and apparent Chiari malformation. In posterior evaluation, mild cerebellar symptoms, mucocutaneous lesions, and a left hemispheric cerebellar lesion were evident. Initially, with the clinical evidence and the radiological study report of a cerebellar tiger-striped lesion, LDD with associated CS was suspected, and a genetic protocol was performed. The protocol included an endoscopy and thyroid ultrasound, and with symptom progression, a new neurosurgical procedure was performed. To complete the approach, we used the clinical criteria for PTEN hamartoma tumor syndrome established in 2013, and CS was diagnosed in the patient. In patients with radiological and clinical suspicion of LDD and CS, it should be mandatory to investigate the presence of other types of tumors due to their association with PTEN hamartomatous tumor syndrome, and in the absence of genetic study, the clinical criteria previously established in the literature should be sufficient to establish the diagnosis.

Full kinetic modeling analysis of [18F]fluorocholine Positron Emission Tomography (PET) at initial diagnosis of high-grade glioma.

PURPOSE: The main objective was to characterize the tracer uptake kinetics of [18F]fluoromethylcholine ([18F]F-CHO) in high-grade gliomas (HGG) through a full PET kinetic modeling approach. Secondarily, we aimed to explore the relationship between the PET uptake measures and the HGG molecular features. MATERIALS AND METHODS: Twenty-four patients with a suspected diagnosis of HGG were prospectively included. They underwent a dynamic brain [18F]F-CHO-PET/CT, from which a tumoral time-activity curve was extracted. The plasma input function was obtained through arterial blood sampling with metabolite correction. These data were fitted to 1- and 2-tissue-compartment models, the best of which was selected through the Akaike information criterion. We assessed the correlation between the kinetic parameters and the conventional static PET metrics (SUVmax, SUVmean and tumor-to-background ratio TBR). We explored the association between the [18F]F-CHO-PET quantitative parameters and relevant molecular biomarkers in HGG. RESULTS: Tumoral time-activity curves in all patients showed a rapid rise of [18F]F-CHO uptake followed by a plateau-like shape. Best fits were obtained with near-irreversible 2-tissue-compartment models. The perfusion-transport constant K1 and the net influx rate Ki showed strong correlation with SUVmax (r = 0.808-0.861), SUVmean (r = 0.794-0.851) and TBR (r = 0.643-0.784), p < 0.002. HGG was confirmed in 21 patients, of which those with methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter showed higher mean Ki (p = 0.020), K1 (p = 0.025) and TBR (p = 0.001) than the unmethylated ones. CONCLUSION: [18F]F-CHO uptake kinetics in HGG is best explained by a 2-tissue-compartment model. The conventional static [18F]F-CHO-PET measures have been validated against the perfusion-transport constant (K1) and the net influx rate (Ki) derived from kinetic modeling. A relationship between [18F]F-CHO uptake rate and MGMT methylation is suggested but needs further confirmation.

Anterior Interhemispheric Approach for the Surgical Treatment of Azygos Anterior Cerebral Artery Aneurysms: A Case Series.

The azygos artery is an uncommon vascular variant of the anterior cerebral artery (ACA). This anomaly is associated in a high percentage with aneurysms. Management of azygos ACA aneurysms represents a surgical challenge. We present five patients who underwent microsurgical treatment for distal azygos ACA aneurysms with complex morphology. Four patients showed subarachnoid hemorrhage (SAH) and one complained of sentinel headache. Early preoperative digital subtraction angiography (DSA) or computerized tomography angiography (CTA) was performed. All patients were treated by surgical clipping via an anterior interhemispheric approach. During follow-up, all patients had a satisfactory outcome, with postoperative angiograms showing complete resolution of aneurysms.

Triple Therapy and Clinical Control in B+ COPD Patients: A Pragmatic, Prospective, Randomized Trial.

INTRODUCTION: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/µL. METHODS: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92µg/umeclidinium (UMEC) 55µg/vilanterol (VI) 22µg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia. RESULTS: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026. CONCLUSIONS: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.

High-Grade Temporal Ganglioglioma in an Older Adult Woman.

Ganglioglioma (GG) is a WHO-grade 1 glioneuronal neoplasm. It is well differentiated with a slow-growing pattern and is composed of a combination of neoplastic ganglion and glial cells. Anaplastic ganglioglioma (AGG) is an extremely rare malignant variant of ganglioglioma, which is not included in the new WHO classification; however, the term is used to talk about gangliogliomas with data of malignancy. AGGs usually occur in children and young adults and are associated with high recurrence and mortality. The authors describe the case of a 62-year-old woman with AGG. She presented with cacosmia, vertigo, nausea, and focal-onset seizures with secondary generalization. Magnetic resonance imaging (MRI) revealed an intra-axial lesion in the left temporal lobe. She underwent microsurgical resection guided by electrocorticography (ECoG), and a diagnosis of AGG based on microscopic morphology and immunohistochemical analysis was obtained. She was discharged a few days after surgery with subtotal resection of the lesion, no additional neurological deficit, and adequate seizure control. AGG is a very rare and poorly studied entity. It is currently a controversial term used to refer to gangliogliomas with signs of malignancy. It occurs mainly in children and young adults with temporal lobe epilepsy. Total resection is the best prognostic factor, given the unknown efficacy of radiotherapy and chemotherapy. In our case, the patient was an adult woman with a subtotal resection followed by concomitant radiotherapy and chemotherapy, obtaining a mean survival similar to that reported in the literature, so it can be thought that there is a benefit obtained with chemotherapy and radiotherapy despite having performed a subtotal resection of the lesion. Further studies are needed to establish clear diagnostic criteria for AGG, and a multicenter database of AGGs is necessary for a better understanding of the pathology and to offer the best treatment and prognosis.

Obstructive Hydrocephalus Due to Posterior Fossa Tumors in Adults: A Comparative Analysis of 3 Surgical Techniques.

BACKGROUND: The main treatments for hydrocephalus due to posterior fossa tumors are tumor resection with or without an external ventricular drain, ventriculoperitoneal shunt (VPS), and endoscopic third ventriculostomy. Although preoperative cerebrospinal fluid diversion by any of these techniques improves clinical outcomes, evidence comparing the efficacy of these techniques is scarce. Therefore, we aimed to retrospectively evaluate each treatment modality. METHODS: This single-center study analyzed 55 patients. Treatments were classified as successful (hydrocephalus resolution with a single surgical event) or failed and compared with a χ2 test. Kaplan-Meier curves and log-rank tests were employed. A Cox proportional hazard model was used to determine relevant covariates predicting outcomes. RESULTS: Mean patient age was 36.3 years, 43.4% of patients were men, and 50.9% of patients presented with uncompensated intracranial hypertension. Mean tumor volume was 33.4 cm3, and extent of resection was 90.85%. Tumor resection with or without an external ventricular drain was successful in 58.82% of cases, VPS was successful in 100%, and endoscopic third ventriculostomy was successful in 76.19% (P = 0.014). Mean follow-up time was 15.12 months. Log-rank test found statistically significant differences between survival curves of treatments (P = 0.016) favoring the VPS group. Postoperative surgical site hematoma was a significant covariate in the Cox model (hazard ratio = 17; 95% confidence ratio, 2.301-81.872; P = 0.004). CONCLUSIONS: This study favored VPS as the most reliable treatment of hydrocephalus due to posterior fossa tumors in adult patient; however, several factors influence clinical outcomes. We proposed an algorithm based on our findings and other authors' findings to facilitate the decision-making process.

[Translated article] Spanish Asthma Management Guidelines (GEMA) v.5.1. Highlights and Controversies.

In this fifth phase of development, the contents of the Spanish Asthma Management Guidelines (GEMA), which include versions 5.0 and 5.1, have undergone a thorough review. The aim here is to set the main changes in context. These could be summarized as follows: DIAGNOSIS: new FENO cut-off and severity classification based on treatment needed to maintain control; INTERMITTENT ASTHMA: a more restrictive concept and treatment extended to include a glucocorticoid/adrenergic combination as needed; MILD ASTHMA: glucocorticoid/adrenergic therapy as needed as an alternative in case of low therapeutic adherence to conventional fixed-dose steroids; SEVERE ASTHMA: readjustment of phenotypes, incorporation of triple therapy in a single inhaler, and criteria for selection of a biologic in severe uncontrolled asthma; OTHERS: specific scoring in childhood asthma, incorporation of certain organizational aspects (care circuits, asthma units, telemedicine), new sections on COVID-19 and nasal polyposis.

Incidence, Mortality, and Trends of Prostate Cancer in Mexico from 2000 to 2019: Results from the Global Burden of Disease Study 2019.

In 2019, the Global Burden of Disease (GBD) estimated that prostate cancer (PC) was the 16th most common cause of death globally in males. In Mexico, PC epidemiology has been studied by a number of metrics and over various periods, although without including the most up-to-date estimates. Herein, we describe and compare the burdens and trends of PC in Mexico and its 32 states from 2000 to 2019. For this study, we extracted online available data from the GBD 2019 to estimate the crude and age-standardized rates (ASR per 100,000 people) of the incidence and mortality of PC. In Mexico, PC caused 27.1 thousand (95% uncertainty intervals, 20.6-36.0 thousand) incident cases and 9.2 thousand (7.7-12.7 thousand) deaths in males of all ages in 2019. Among the states, Sinaloa had the greatest ASR of incidence, and Guerrero had the highest mortality. The burden of PC showed an increasing trend, although the magnitude of change differed between metrics and locations. We found both an increasing national trend and subnational variation in the burden of PC. Our results confirm the need for updated and timely estimates to design effective diagnostic and treatment campaigns in locations where the burden of PC is the highest.

Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease of the joints that has been associated with variation in the peripheral blood methylome. In this study, we aim to identify epigenetic variation that is associated with the response to tumor necrosis factor inhibitor (TNFi) therapy. METHODS: Peripheral blood genome-wide DNA methylation profiles were analyzed in a discovery cohort of 62 RA patients at baseline and at week 12 of TNFi therapy. DNA methylation of individual CpG sites and enrichment of biological pathways were evaluated for their association with drug response. Using a novel cell deconvolution approach, altered DNA methylation associated with TNFi response was also tested in the six main immune cell types in blood. Validation of the results was performed in an independent longitudinal cohort of 60 RA patients. FINDINGS: Treatment with TNFi was associated with significant longitudinal peripheral blood methylation changes in biological pathways related to RA (FDR<0.05). 139 biological functions were modified by therapy, with methylation levels changing systematically towards a signature similar to that of healthy controls. Differences in the methylation profile of T cell activation and differentiation, GTPase-mediated signaling, and actin filament organization pathways were associated with the clinical response to therapy. Cell type deconvolution analysis identified CpG sites in CD4+T, NK, neutrophils and monocytes that were significantly associated with the response to TNFi. INTERPRETATION: Our results show that treatment with TNFi restores homeostatic blood methylation in RA. The clinical response to TNFi is associated to methylation variation in specific biological pathways, and it involves cells from both the innate and adaptive immune systems. FUNDING: The Instituto de Salud Carlos III.

Spanish COPD Guideline (GesEPOC) Update: Comorbidities, Self-Management and Palliative Care. / Actualización de la Guía Española de la EPOC (GesEPOC): comorbilidades, automanejo y cuidados paliativos.

The current health care models described in GesEPOC indicate the best way to make a correct diagnosis, the categorization of patients, the appropriate selection of the therapeutic strategy and the management and prevention of exacerbations. In addition, COPD involves several aspects that are crucial in an integrated approach to the health care of these patients. The evaluation of comorbidities in COPD patients represents a healthcare challenge. As part of a comprehensive assessment, the presence of comorbidities related to the clinical presentation, to some diagnostic technique or to some COPD-related treatments should be studied. Likewise, interventions on healthy lifestyle habits, adherence to complex treatments, developing skills to recognize the signs and symptoms of exacerbation, knowing what to do to prevent them and treat them within the framework of a self-management plan are also necessary. Finally, palliative care is one of the pillars in the comprehensive treatment of the COPD patient, seeking to prevent or treat the symptoms of a disease, the side effects of treatment, and the physical, psychological and social problems of patients and their caregivers. Therefore, the main objective of this palliative care is not to prolong life expectancy, but to improve its quality. This chapter of GesEPOC 2021 presents an update on the most important comorbidities, self-management strategies, and palliative care in COPD, and includes a recommendation on the use of opioids for the treatment of refractory dyspnea in COPD.

Cranial aseptic osteomyelitis associated with pyoderma gangrenosum.

Neutrophilic dermatoses include a heterogeneous group of entities. Uncommonly, they can accumulate aseptic neutrophilic abscesses in other tissues in addition to the skin. A 34-year-old female complained of a headache which was unresponsive to usual drugs. A TAC revealed an osteolytic lesion in the right parietal bone. The biopsy showed osteomyelitis. One year later, pyoderma gangrenosum appeared in the anterior aspect of both legs. The headache and the cutaneous lesions disappeared after treatment with oral prednisone. The bone involvement in the background of neutrophilic dermatoses is exceptional. Usually, it involves children in the context of chronic recurrent multiple osteomyelitis (CRMO). Only two cases have been described in adults. One of them was a 26-year-old woman who had had CRMO since childhood, and the other one in contiguity with the cutaneous lesions of pyoderma gangrenosum.

Spanish COPD Guidelines (GesEPOC) 2021: Updated Pharmacological treatment of stable COPD. / Actualización 2021 de la Guía Española de la EPOC (GesEPOC). Tratamiento farmacológico de la EPOC estable.

The Spanish COPD Guidelines (GesEPOC) were first published in 2012, and since then have undergone a series of updates incorporating new evidence on the diagnosis and treatment of COPD. GesEPOC was drawn up in partnership with scientific societies involved in the treatment of COPD and the Spanish Patients' Forum. Their recommendations are based on an evaluation of the evidence using GRADE methodology, and a narrative description of the evidence in areas in which GRADE cannot be applied. In this article, we summarize the recommendations on the pharmacological treatment of stable COPD based on 9 PICO questions. COPD treatment is a 4-step process: 1) diagnosis, 2) determination of the risk level, 3) initial and subsequent inhaled therapy, and 4) identification and management of treatable traits. For the selection of inhaled therapy, high-risk patients are divided into 3 phenotypes: non-exacerbator, eosinophilic exacerbator, and non-eosinophilic exacerbator. Some treatable traits are general and should be investigated in all patients, such as smoking or inhalation technique, while others affect severe patients in particular, such as chronic hypoxemia and chronic bronchial infection. COPD treatment is based on long-acting bronchodilators with single agents or in combination, depending on the patient's risk level. Eosinophilic exacerbators must receive inhaled corticosteroids, while non-eosinophilic exacerbators require a more detailed evaluation to choose the best therapeutic option. The new GesEPOC also includes recommendations on the withdrawal of inhaled corticosteroids and on indications for alpha-1 antitrypsin treatment. GesEPOC offers a more individualized approach to COPD treatment tailored according to the clinical characteristics of patients and their level of complexity.

Spanish Asthma Management Guidelines (GEMA) VERSION 5.1. Highlights and Controversies. / Guía española para el manejo del asma (GEMA) versión 5.1. Aspectos destacados y controversias.

In this fifth phase of development, the contents of the Spanish Asthma Management Guidelines (GEMA), which include versions 5.0 and 5.1, have undergone a thorough review. The aim here is to set the main changes in context. These could be summarized as follows: DIAGNOSIS: new FENO cut-off and severity classification based on treatment needed to maintain control; INTERMITTENT ASTHMA: a more restrictive concept and treatment extended to include a glucocorticoid/adrenergic combination as needed; MILD ASTHMA: glucocorticoid/adrenergic therapy as needed as an alternative in case of low therapeutic adherence to conventional fixed-dose steroids; SEVERE ASTHMA: readjustment of phenotypes, incorporation of triple therapy in a single inhaler, and criteria for selection of a biologic in severe uncontrolled asthma; OTHERS: specific scoring in childhood asthma, incorporation of certain organizational aspects (care circuits, asthma units, telemedicine), new sections on COVID-19 and nasal polyposis.

Cranial aseptic osteomyelitis associated with pyoderma gangrenosum. / Osteomielitis aséptica craneal asociada a pioderma gangrenoso.

Neutrophilic dermatoses include a heterogeneous group of entities. Uncommonly, they can accumulate aseptic neutrophilic abscesses in other tissues in addition to the skin. A 34-year-old female complained of a headache which was unresponsive to usual drugs. A TAC revealed an osteolytic lesion in the right parietal bone. The biopsy showed osteomyelitis. One year later, pyoderma gangrenosum appeared in the anterior aspect of both legs. The headache and the cutaneous lesions disappeared after treatment with oral prednisone. The bone involvement in the background of neutrophilic dermatoses is exceptional. Usually, it involves children in the context of chronic recurrent multiple osteomyelitis (CRMO). Only two cases have been described in adults. One of them was a 26-year-old woman who had had CRMO since childhood, and the other one in contiguity with the cutaneous lesions of pyoderma gangrenosum.

Cardiovascular mortality and cardiovascular event rates in patients with inflammatory rheumatic diseases in the CARdiovascular in rheuMAtology (CARMA) prospective study-results at 5 years of follow-up.

OBJECTIVES: To determine cardiovascular (CV) mortality and incidence of the first CV event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD) after 5 years of follow-up. METHODS: This is an analysis of the CARdiovascular in rheMAatology (CARMA) study after 5 years of follow-up. It includes patients with RA (n = 775), AS (n = 738) and PsA (n = 721), and individuals without CIRD (n = 677) attending outpatient rheumatology clinics from 67 public hospitals in Spain. Descriptive analyses were performed for the CV mortality at 5 years. The Systematic COronary Risk Evaluation (SCORE) function at 5 years was calculated to determine the expected risk of CV mortality. Poisson models were used to estimate the incidence rates of the first CVE. Hazard ratios of the risk factors involved in the development of the first CVE were evaluated using the Weibull proportional hazard model. RESULTS: Overall, 2382 subjects completed the follow-up visit at 5 years. Fifteen patients died due to CVE. CV deaths observed in the CIRD cohort were lower than that predicted by SCORE risk charts. The highest incidence rate of CVE [7.39 cases per 1000 person-years (95% CI 4.63, 11.18)] was found in PsA patients. However, after adjusting for age, sex and CV risk factors, AS was the inflammatory disease more commonly associated with CVE at 5 years [hazard ratio 4.60 (P =0.02)], compared with those without CIRD. CONCLUSIONS: Cardiovascular mortality in patients with CIRD at 5 years of follow-up is lower than estimated. Patients with AS have a higher risk of developing a first CVE after 5 years of follow-up.

Expert Recommendations on the Interleukin 6 Blockade in Patients with Rheumatoid Arthritis. / Recomendaciones de experto sobre el bloqueo de la interleucina 6 en pacientes con artritis reumatoide.

OBJECTIVE: To draft recommendations on interleukin 6 (IL-6) blockade in rheumatoid arthritis (RA), based on best evidence and experience. METHODS: A group of 10 experts on IL-6 blockade in RA was selected. The 2 coordinators formulated 23 questions about IL-6 blockade (indications, efficacy, safety, etc.). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (Medline, EMBASE and the Cochrane Library were searched). Two different reviewers selected the articles. Evidence tables were created. At the same time, European League Against Rheumatism and American College of Rheumatology abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted on in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Centre for Evidence Based Medicine and the level of agreement with the Delphi technique (2 rounds). Agreement was established if at least 80% of the experts voted yes (yes/no). RESULTS: The 8 preliminary recommendations were accepted after the Delphi process. They covered aspects such as the use of these therapies in monotherapy, in combination, in patients with refractory disease or intolerant patients, response evaluation, optimization and risk management. CONCLUSIONS: The manuscript aims to solve frequently asked questions and aid in decision making strategies when treating RA patients with IL-6 blockade.

Tomografía por emisión de positrones en el diagnóstico de sarcoidosis y síndrome de Löfgren / Tomography by emission of positrons in the diagnosis of sarcoidosis and Löfgren's syndrome

La sarcoidosis es una enfermedad granulomatosa no caseificante, multisistémica, de causa desconocida, que compromete el pulmón y los ganglios linfáticos mediastinales entre el 90-95 por ciento de los casos. También puede afectar otros órganos como las glándulas salivales, piel, ojos, hígado, bazo, corazón, huesos y sistema nervioso central. El compromiso torácico representa la principal causa de morbilidad con unas 10/100 000 personas al año y mortalidad. Nuestro estudio tuvo como objetivo presentar a un paciente de 45 años de edad atendido por tener manifestaciones clínicas, paraclínicas y radiográficas que permitieron establecer, sin confirmar mediante estudio histológico, el diagnóstico de una forma aguda de sarcoidosis. Su forma clínica de expresión coincidió con el síndrome de Löfgren con ensanchamiento mediastinal bilateral por linfoadenopatía hiliar, síndrome febril, eritema nudoso y artritis aguda en miembros inferiores, que desarrollan entre un 20-30 por ciento de los pacientes con sarcoidosis. Se le realizó una tomografía por emisión de positrones, cuyos resultados ofrecieron elementos diagnósticos propios de un proceso inflamatorio pulmonar alejado de las características propias de una neoplasia maligna. Después de una profunda evaluación del riesgo-beneficio, se impuso tratamiento inmunosupresor con esteroides a dosis elevadas y seguimiento estrecho. Observamos una evolución muy positiva e inmediata desde el punto de vista clínico y radiográfico. Luego de varias semanas de tratamiento se apreciaron los cambios con marcada mejoría hasta pasados 3 meses que constatamos prácticamente una casi desaparición de las imágenes radiográficas(AU)

Sarcoidosis is a multisystemic, non-caseating granulomatous disease of unknown cause that involves the lung and the mediastinal lymph nodes in between 90 percent and 95 percent of cases. It can also affect other organs, such as the salivary glands, skin, eyes, liver, spleen, heart, bones, and central nervous system. Thoracic involvement represents the main cause of morbidity and mortality in patients with this entity, which occurs in about 10 / 100,000 people a year. Our study aimed to present a 45-year-old patient treated for presenting clinical, paraclinical and radiological manifestations that allow the diagnosis of an acute form of sarcoidosis to be established without confirming by histological study. Its clinical form of expression showed the presence of Löfgren's syndrome with bilateral mediastinal widening due to hilar lymphadenopathy, febrile syndrome, erythema nodosum, and acute arthritis in the lower limbs, which 20-30 percent of patients with sarcoidosis develop. A positron emission tomography scan was performed and its results offered us diagnostic elements typical of a pulmonary inflammatory process far from the characteristics of a malignant neoplastic process(AU)

Development of a thin layer chromatography method for plasma correction of [18F]fluorocholine metabolites in positron emission tomography quantification studies in humans.

INTRODUCTION: After its intravenous injection, [18F]fluorocholine is oxidized by choline-oxidase into its main plasma metabolite, [18F]fluorobetaine. If PET kinetic modeling quantification of [18F]fluorocholine uptake is intended, the plasma input time-activity-curve of the parent tracer must be obtained, i.e., the fraction of the total plasma radioactivity corresponding to the nonmetabolized [18F]fluorocholine at each time has to be known. Hence our aim was to develop an easy-routine Thin-Layer-Chromatography (TLC) method to separate and quantify the relative fractions of [18F]fluorocholine and [18F]fluorobetaine as a function of time during PET imaging in humans. METHODS: First, we tested several combinations of solvents systems and layers to select the one showing the best resolution on non-radioactive standards. Thereafter, [18F]fluorobetaine was obtained through chemical oxidation of an [18F]fluorocholine sample at diferent incubation times and we applied the selected TLC-system to aliquots of this oxidation solution, both in a saline and in human deproteinized plasma matrices. The plates were detected by a radio-TLC-scanner. This TLC-system was finally applied to arterial plasma samples from 9 patients with high-grade-glioma undergoing brain PET imaging and a parent fraction curve was obtained in each of them. RESULTS: A TLC-system based on Silica-Gel-60//MeOH-NH3 was selected from the choline/betaine non-radioactive standards assay. Radiochromatograms of [18F]fluorocholine oxidation solution yielded two separated and well-defined peaks, Rf = 0,03 ([18F]fluorocholine) and Rf = 0.78 (18F]fluorobetaine) consistent with those observed on non-radioactive standards. During the oxidation, the [18F]fluorocholine radioactivity peak decreased progressively at several incubation times, while the other peak ([18F]fluorobetaine) increased accordingly. The mean values of the parent fraction of [18F]fluorocholine of the 9 patients studied (mean+/-SD) were 94% ±â€¯6%, 58% ±â€¯15%, 43% ±â€¯10%, 39% ±â€¯6% and 37% ±â€¯6% at 2.8 min, 5.8 min, 8.8 min, 11.7 min and 14.7 min post-injection, respectively. CONCLUSIONS: We have developed a TLC-system, easy to perform in a standard radiopharmacy unit, that enables the metabolite correction of arterial input function of [18F]fluorocholine in patients undergoing PET oncologic quantitative imaging.

Lifestyle and comorbid conditions as risk factors for community-acquired pneumonia in outpatient adults (NEUMO-ES-RISK project).

Introduction: Information about community-acquired pneumonia (CAP) risk in primary care is limited. We assess different lifestyle and comorbid conditions as risk factors (RF) for CAP in adults in primary care. Methods: A retrospective-observational-controlled study was designed. Adult CAP cases diagnosed at primary care in Spain between 2009 and 2013 were retrieved using the National Surveillance System of Primary Care Data (BiFAP). Age-matched and sex-matched controls were selected by incidence density sampling (ratio 2:1). Associations are presented as percentages and OR. Binomial regression models were constructed to avoid bias effects. Results: 51 139 patients and 102 372 controls were compared. Mean age (SD) was 61.4 (19.9) years. RF more significantly linked to CAP were: HIV (OR [95% CI]: 5.21 [4.35 to 6.27]), chronic obstructive pulmonary disease (COPD) (2.97 [2.84 to 3.12]), asthma (2.16 [2.07,2.26]), smoking (1.96 [1.91 to 2.02]) and poor dental hygiene (1.45 [1.41 to 1.49]). Average prevalence of any RF was 82.2% in cases and 69.2% in controls (2.05 [2.00 to 2.10]). CAP rate increased with the accumulation of RF and age: risk associated with 1RF was 1.42 (1.37 to 1.47) in 18-60-year-old individuals vs 1.57 (1.49 to 1.66) in >60 years of age, with 2RF 1.88 (1.80 to 1.97) vs 2.35 (2.23, 2.48) and with ≥ 3 RF 3.11 (2.95, 3.30) vs 4.34 (4.13 to 4.57). Discussion: Prevalence of RF in adult CAP in primary care is high. Main RFs associated are HIV, COPD, asthma, smoking and poor dental hygiene. Our risk stacking results could help clinicians identify patients at higher risk of pneumonia.

Incidence of first cardiovascular event in Spanish patients with inflammatory rheumatic diseases: prospective data from the CARMA project.

OBJECTIVES: To determine the incidence and risk factors of first cardiovascular event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD). METHODS: Analysis of data after 2.5 years of follow-up from the prospective study CARMA project, that includes patients with CIRD [rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA)] and matched individuals without CIRD from 67 hospitals in Spain. CVE cumulative incidence per 1000 patients was calculated after 2.5 years from the start of the project. Weibull proportional hazard model was used to calculate hazard ratio (HR) and 95% confidence interval (95% CI) of the risk factors. RESULTS: 2595 (89.1%) patients completed the 2.5 years of follow-up visit. Cumulative incidence of CVE in patients with CIRD was 15.30 cases per 1000 patients (95% CI: 12.93-17.67), being higher in the subgroup with AS; 22.03 (95% CI: 11.01-33.04). Patients with AS (HR: 4.11; 95% CI: 1.07-15.79), those with older age (HR: 1.09; 95% CI: 1.05-1.13), systolic hypertension (HR: 1.02; 95% CI: 1.00-1.04) and long duration of the disease (HR: 1.07; 95% CI: 1.03-1.12) were at higher risk of first CVE during the 2.5 years of follow-up. In contrast, female gender was a protective factor (HR: 0.43; 95% CI: 0.18-1.00). CONCLUSIONS: Among CIRD patients prospectively followed-up at rheumatology outpatient clinics, those with AS show higher risk of first CVE. Besides cardiovascular risk factors, such as hypertension, being a man and older as well as having a long disease duration increase the risk of CVE in patients with CIRD.