Psoriasis induced by antiTNF therapy in inflammatory bowel disease: Therapeutic management and evolution of both diseases in a nationwide cohort study.

BACKGROUND: some patients with inflammatory bowel disease (IBD) treated with antiTNF develop drug-induced psoriasis (antiTNF-IP). Several therapeutic strategies are possible. AIMS: to assess the management of antiTNF-IP in IBD, and its impact in both diseases. METHODS: patients with antiTNF-IP from ENEIDA registry were included. Therapeutic strategy was classified as continuing the same antiTNF, stopping antiTNF, switch to another antiTNF or swap to a non-antiTNF biologic. IP severity and IBD activity were assessed at baseline and 16, 32 and 54 weeks. RESULTS: 234 patients were included. At baseline, antiTNF-IP was moderate-severe in 60 % of them, and IBD was in remission in 80 %. Therapeutic strategy was associated to antiTNF-IP severity (p < 0.001). AntiTNF-IP improved at week 54 with all strategies, but continuing with the same antiTNF showed the worst results (p = 0.042). Among patients with IBD in remission, relapse was higher in those who stopped antiTNF (p = 0.025). In multivariate analysis, stopping antiTNF, trunk and palms and soles location were associated with antiTNF-IP remission; female sex and previous surgery in Crohn´s disease with IBD relapse. CONCLUSION: skin lesions severity and IBD activity seem to determine antiTNF-IP management. Continuing antiTNF in mild antiTNF-IP, and swap to ustekinumab or switch to another antiTNF in moderate-severe cases, are suitable strategies.

Initial management of intraabdominal abscesses and preventive strategies for abscess recurrence in penetrating Crohn's disease: a national multicenter study based on ENEIDA registry.

INTRODUCTION: Intra-abdominal abscesses complicating Crohn's disease (CD) are a challenging situation. Their management, during the hospitalization and after resolution, is still unclear. METHODS: Adult patients with CD complicated with intraabdominal abscess who required hospitalization were included from the prospectively maintained ENEIDA registry from GETECCU. Initial strategy effectiveness and safety to resolve abscess was assessed. Survival analysis was performed to evaluate recurrence risk. Predictive factors associated with resolution were evaluated by multivariate regression and predictive factors associated with recurrence were assessed by Cox regression. RESULTS: 520 patients from 37 Spanish hospitals were included; 322 (63%) were initially treated with antibiotics alone, 128 (26%) with percutaneous drainage, and 54 (17%) with surgical drainage. The size of the abscess was critical to the effectiveness of each treatment. In abscesses < 30mm, the antibiotic was as effective as percutaneous or surgical drainage. However, in larger abscesses, percutaneous or surgical drainage was superior. In abscesses > 50mm, surgery was superior to percutaneous drainage, although it was associated with a higher complication rate. After abscess resolution, luminal resection was associated with a lower 1-year abscess recurrence risk (HR 0.43, 95% CI 0.24-0.76). However, those patients who initiated anti-TNF therapy had a similar recurrence risk whether luminal resection had been performed. CONCLUSIONS: Small abscesses (<30mm) can be managed with antibiotics alone, while larger ones require drainage. Percutaneous drainage will be effective and safer than surgery in many cases. After discharge, anti-TNF therapy reduces abscess recurrence risk in a similar way to bowel resection.

Homogeneous immunoassay for cyclopiazonic acid based upon mimotopes and upconversion-resonance energy transfer.

Strains of Penicillium spp. are used for fungi-ripened cheeses and Aspergillus spp. routinely contaminate maize and other crops. Some of these strains can produce toxic secondary metabolites (mycotoxins), including the neurotoxin α-cyclopiazonic acid (CPA). In this work, we developed a homogeneous upconversion-resonance energy transfer (UC-RET) immunoassay for the detection of CPA using a novel epitope mimicking peptide, or mimotope, selected by phage display. CPA-specific antibody was used to isolate mimotopes from a cyclic 7-mer peptide library in consecutive selection rounds. Enrichment of antibody binding phages was achieved, and the analysis of individual phage clones revealed four different mimotope peptide sequences. The mimotope sequence, ACNWWDLTLC, performed best in phage-based immunoassays, surface plasmon resonance binding analyses, and UC-RET-based immunoassays. To develop a homogeneous assay, upconversion nanoparticles (UCNP, type NaYF4:Yb3+, Er3+) were used as energy donors and coated with streptavidin to anchor the synthetic biotinylated mimotope. Alexa Fluor 555, used as an energy acceptor, was conjugated to the anti-CPA antibody fragment. The homogeneous single-step immunoassay could detect CPA in just 5 min and enabled a limit of detection (LOD) of 30 pg mL-1 (1.5 µg kg-1) and an IC50 value of 0.36 ng mL-1. No significant cross-reactivity was observed with other co-produced mycotoxins. Finally, we applied the novel method for the detection of CPA in spiked maize samples using high-performance liquid chromatography coupled to a diode array detector (HPLC-DAD) as a reference method.

Limited Chest Ultrasound to Replace CXR in Diagnosis of Pneumothorax Post Image-Guided Transthoracic Interventions.

PURPOSE: To assess the diagnostic accuracy of limited chest ultrasound in detecting pneumothorax following percutaneous transthoracic needle interventions using chest X-ray (CXR) as the reference standard. METHODS: With IRB approval, after providing consent, asymptomatic patients after percutaneous transthoracic needle interventions were enrolled to undergo limited chest ultrasound in addition to CXR. A chest Radiologist blinded to the patient's prior imaging performed a bedside ultrasound, scanning only the first 3 anterior intercostal spaces. Pneumothorax diagnosed on CXR was categorized as small or large and on ultrasound as grades 1, 2, or 3 when detected in 1, 2, or 3 intercostal spaces, respectively. RESULTS: 38 patients underwent 36 biopsies (34 lungs, 1 pleura, and 1 mediastinum) and 2 coil localizations. CXR showed pneumothorax in 13 patients. Ultrasound was positive in 10 patients, with 9 true-positives, 1 false-positive, 4 false-negatives, and 24 true-negatives. The false positive results were due to apical subpleural bullae. The false-negative results occurred in 2 small apical and 2 focal pneumothoraces at the needle entry sites. Four pneumothoraces were categorized as large on CXR, all of which were categorized as grade 3 on ultrasound. Sensitivity and specificity of US for detection of pneumothorax of any size were 69.23% (95%CI 38.6%, 90.1%) and 96.0% (95%CI 79.6%, 99.9%), and for detection of large pneumothorax were 100% (95%CI 39.8%, 100%) and 100% (95%CI 89.7%, 100%). CONCLUSIONS: Results of this prospective study is promising. Limited chest ultrasound could potentially replace CXR in the management of postpercutaneous transthoracic needle intervention patients.

Impact of Biological Agents on Postsurgical Complications in Inflammatory Bowel Disease: A Multicentre Study of Geteccu.

BACKGROUND: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. AIMS: To evaluate the impact of biologics on the risk of PC. METHODS: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. RESULTS: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27). CONCLUSIONS: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.

Recombinant Peptide Mimetic NanoLuc Tracer for Sensitive Immunodetection of Mycophenolic Acid.

Mycophenolic acid (MPA) is an immunosuppressant drug commonly used to prevent organ rejection in transplanted patients. MPA monitoring is of great interest due to its small therapeutic window. In this work, a phage-displayed peptide library was used to select cyclic peptides that bind to the MPA-specific recombinant antibody fragment (Fab) and mimic the behavior of MPA. After biopanning, several phage-displayed peptides were isolated and tested to confirm their epitope-mimicking nature in phage-based competitive immunoassays. After identifying the best MPA mimetic (ACEGLYAHWC with a disulfide constrained loop), several immunoassay approaches were tested, and a recombinant fusion protein containing the peptide sequence with a bioluminescent enzyme, NanoLuc, was developed. The recombinant fusion enabled its direct use as the tracer in competitive immunoassays without the need for secondary antibodies or further labeling. A bioluminescent sensor, using streptavidin-coupled magnetic beads for the immobilization of the biotinylated Fab antibody, enabled the detection of MPA with a detection limit of 0.26 ng mL-1 and an IC50 of 2.9 ± 0.5 ng mL-1. The biosensor showed good selectivity toward MPA and was applied to the analysis of the immunosuppressive drug in clinical samples, of both healthy and MPA-treated patients, followed by validation by liquid chromatography coupled to diode array detection.

Competitive upconversion-linked immunoassay using peptide mimetics for the detection of the mycotoxin zearalenone.

Due to increasing food safety standards, the analysis of mycotoxins has become essential in the food industry. In this work, we have developed a competitive upconversion-linked immunosorbent assay (ULISA) for the analysis of zearalenone (ZEA), one of the most frequently encountered mycotoxins in food worldwide. Instead of a toxin-conjugate conventionally used in competitive immunoassays, we designed a ZEA mimicking peptide extended by a biotin-linker and confirmed its excellent suitability to mimic ZEA by nuclear magnetic resonance (NMR) and surface plasmon resonance (SPR) analysis. Upconversion nanoparticles (UCNP, type NaYF4:Yb,Tm) served as background-free optical label for the detection of the peptide mimetic in the competitive ULISA. Streptavidin-conjugated UCNPs were prepared by click reaction using an alkyne-PEG-neridronate linker. The UCNP conjugate clearly outperformed conventional labels such as enzymes or fluorescent dyes. With a limit of detection of 20 pg mL-1 (63 pM), the competitive ULISA is well applicable to the detection of ZEA at the levels set by the European legislation. Moreover, the ULISA is specific for ZEA and its metabolites (α- and ß-zearalenol) without significant cross-reactivity with other related mycotoxins. We detected ZEA in spiked and naturally contaminated maize samples using liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) as a reference method to demonstrate food analysis in real samples.

Early treatment with anti-tumor necrosis factor agents improves long-term effectiveness in symptomatic stricturing Crohn's disease.

BACKGROUND: There is limited evidence on the effectiveness of biological therapy in stricturing complications in patients with Crohn's disease. AIM: The study aims to determine the effectiveness of anti-tumor necrosis factor (TNF) agents in Crohn's disease complicated with symptomatic strictures. METHODS: In this multicentric and retrospective study, we included adult patients with symptomatic stricturing Crohn's disease receiving their first anti-TNF therapy, with no previous history of biological, endoscopic or surgical therapy. The effectiveness of the anti-TNF agent was defined as a composite outcome combining steroid-free drug persistence with no use of new biologics or immunomodulators, hospital admission, surgery or endoscopic therapy during follow-up. RESULTS: Overall, 262 patients with Crohn's disease were included (53% male; median disease duration, 35 months, 15% active smokers), who received either infliximab (N = 141, 54%) or adalimumab (N = 121, 46%). The treatment was effective in 87% and 73% of patients after 6 and 12 months, respectively, and continued to be effective in 26% after a median follow-up of 40 months (IQR, 19-85). Nonetheless, 15% and 21% of individuals required surgery after 1 and 2 years, respectively, with an overall surgery rate of 32%. Postoperative complications were identified in 15% of patients, with surgical site infection as the most common. Starting anti-TNF therapy in the first 18 months after the diagnosis of Crohn's disease or the identification of stricturing complications was associated with a higher effectiveness (HR 1.62, 95% CI 1.18-2.22; and HR 1.55, 95% CI 1.1-2.23; respectively). Younger age, lower albumin levels, strictures located in the descending colon, concomitant aminosalicylates use or presence of lymphadenopathy were associated with lower effectiveness. CONCLUSIONS: Anti-TNF agents are effective in approximately a quarter of patients with Crohn's disease and symptomatic intestinal strictures, and 68% of patients are free of surgery after a median of 40 months of follow-up. Early treatment and some potential predictors of response were associated with treatment success in this setting.

Panorama histórico de la enfermedad diarreica aguda en México y el futuro de su prevención / Historical overview of acute infectious diarrhea in Mexico and future preventive strategies

Resumen: Objetivo: Revisar los aspectos epidemiológicos de la enfermedad diarreica aguda (EDA) a través de la historia de México y analizar las estrategias que potencialmente podrán prevenir su aparición en la población mexicana. Material y métodos: Se realizó una búsqueda sistematizada utilizando los siguientes descriptores de las ciencias de la salud: diarrea, morbilidad, mortalidad, México y promoción de la salud de los últimos 20 años (1878-2018). Resultados: Se obtuvieron más de 8 600 artículos que fueron evaluados en función de los objetivos de la presente publicación. Conclusión: Como resultado de una revisión sistemática se observó que, gracias a las estrategias implementadas a lo largo del tiempo, se ha logrado graduar los matices de riesgo de la EDA; ello permite ahora plantear estrategias que guiarán a la prevención de ese padecimiento, de la mano de políticas que incluyan aspectos higiénico-dietéticos, innovaciones farmacéuticas y aplicaciones tecnológicas en medidas sanitarias.

Abstract: Objective: To analyze the epidemiological aspects of AID through Mexican history and the potential strategies to prevent AID in Mexican population. Materials and methods: A systematic review was performed exploring the key words, diarrhea, morbidity, mortality, Mexico, health promotion for the last 20 years (1978-2018). Results: Over 8 600 articles were obtained; all of them were evaluated to consider those follow the aim of the present work. Conclusion: The result of the performed systematic review denoted the influence of AID in Mexican public health policy the adopted actions diminished the AID's associated risks and allowed future strategies to prevent it; those actions must include hygienic and dietetic measures, pharmaceutical innovations and technological tools applied to health policies.

Reference values for mid-diastolic right ventricular volume in population referred for cardiac computed tomography: An additional diagnostic value to cardiac computed tomography.

BACKGROUND: While an assessment of the right ventricular (RV) size remains challenging, the entire RV is can be imaged on coronary computed tomography angiography (CCTA) studies. With prospective ECG-triggering, the RV end diastolic volume (RVEDV) cannot be measured; however, the RV mid-diastolic volume (RVMDV) can still be measured accurately from routine CCTA data sets. The objective of this study is to establish normal reference values for RVMDV. METHODS: Right ventricular mid-diastolic volumes were measured in 4855 consecutive patients undergoing prospectively ECG-triggered coronary CTA. All patients with known cardiac or pulmonary disease (coronary artery disease, myocardial infarction, revascularization, heart failure, pulmonary hypertension, congenital heart disease, valvular heart disease, atrial fibrillation, implantable cardiac defibrillator implantation, cardiac transplant, or cardiac surgery) or smoking history (3313 patients) were excluded. RESULTS: 1542 patients were analyzed (mean age 56.4 ± 11.1 years, mean BSA 1.96 ± 0.26 and 47% male). The mean RVMDV for men and women was 168.6 ± 37.6 mL and 117.6 ± 26.4 mL, respectively. Mean BSA-indexed RVMDV was 80.0 ± 15.3 mL/m2 and 64.1 ± 12.2 mL/m2 for men and women, respectively. The presence of hypertension and diabetes did not have an impact on these values. RVMDV and BSA-indexed RVMDV were lower in women and in older individuals. CONCLUSION: Normal reference ranges for RVMDV were established using prospectively ECG-triggered coronary CTA studies. This data can be used to identify patients with abnormal RV volumes and potentially RV dysfunction, adding incremental diagnostic value to routine CCTA studies.

Development and comparison of mimotope-based immunoassays for the analysis of fumonisin B1.

Mycotoxins can be found as natural contaminants in many foods and feeds, and owing to their toxic effects, it is essential to detect them before they enter the food chain. An interesting approach for the analysis of mycotoxins by competitive immunoassays is the use of epitope-mimicking peptides, or mimotopes, which can replace the toxin conjugates traditionally used in such assays. Mimotopes can be selected from phage-displayed peptide libraries even without any prior knowledge of the antibody-antigen interaction, and after identifying the target specific clones, individual clones can be efficiently amplified in bacteria and used directly in the immunoassay. Following such approach, we have previously selected and identified a dodecapeptide which functions as a mimotope for the mycotoxin fumonisin B1. In this work, we present the development and comparison of various immunoassays based on this mimotope, named A2, which has been used in the phage-displayed format in which it was selected, but also as a fluorescent recombinant fusion protein or as a synthetic peptide. The highest sensitivity was obtained with a magnetic bead-based assay using the synthetic peptide and enzymatic detection which provided a detection limit of 0.029 ng mL-1. Analysis of the binding kinetics by surface plasmon resonance (SPR) further reinforced the suitability of the synthetic peptide for the competitive immunoassays, as this mimotope showed a slightly lower affinity for the target antibody in comparison with the recombinant fusion protein. Graphical abstract.

The 2018 Nobel Prize in Chemistry: phage display of peptides and antibodies.

One-half of the 2018 Nobel Prize in Chemistry was awarded jointly to George P. Smith and Sir Gregory P. Winter "for the phage display of peptides and antibodies". This feature article summarizes significant achievements leading to the development of phage display of peptides and antibodies, where a bacteriophage is genetically modified to display peptides and proteins, with the primary aim of producing new biopharmaceuticals. These significant achievements are proven to be useful for the development of phage-based bioassays and biosensors.

Bioinspired recognition elements for mycotoxin sensors.

Mycotoxins are low molecular weight molecules produced as secondary metabolites by filamentous fungi that can be found as natural contaminants in many foods and feeds. These toxins have been shown to have adverse effects on both human and animal health, and are the cause of significant economic losses worldwide. Sensors for mycotoxin analysis have traditionally applied elements of biological origin for the selective recognition purposes. However, since the 1970s there has been an exponential growth in the use of genetically engineered or synthetic biomimetic recognition elements that allow some of the limitations associated with the use of natural receptors for the analyses of these toxins to be circumvented. This review provides an overview of recent advances in the application of bioinspired recognition elements, including recombinant antibodies, peptides, aptamers, and molecularly imprinted polymers, to the development of sensors for mycotoxins based on different transduction elements. Graphical abstract Novel analytical methods based on bioinspired recognition elements, such as recombinant antibodies, peptides, aptamers, and molecularly imprinted polymers, can improve the detection of mycotoxins and provide better tools than their natural counterparts to ensure food safety.

Terremotos y salud: la organización de los servicios de atención médica / Earthquakes and healthcare: the organization of the services of medical attention

Resumen Los sistemas de salud están expuestos a diversos desastres que pueden impactar en la eficacia y calidad de servicio que ofrecen. Por ello, es importante contar con elementos que les permitan tener una adecuada infraestructura y organización. Este texto delinea algunos de estos elementos y acciones, cuya incorporación en los hospitales permitirá brindar una respuesta oportuna en caso de desastre. Se expone el uso del triage como un instrumento que regula el ingreso de los pacientes a los hospitales y se analiza cómo el inadecuado uso de éste durante una situación de desastre puede cobrar la vida de las personas lesionadas. Por último, se propone la preparación de un hospital ante posibles desastres y se retoma la experiencia de otro en el marco de los sismos ocurridos en México en 2017.

Abstract Health care systems are exposed to several natural disasters that could affect the effectiveness and quality of the services they offer. For this reason it is important to bring out the necessary elements that allow them a suitable organization and infrastructure. In this context some of these elements are drafted as well as a specific set of actions whose inclusion in the hospitals will allow for an optimal answer in case of natural disaster. The use of the triage is analyzed as an instrument that regulates the patient admission to the hospitals. Also, it is shown how the inadequate use of this tool during an emergency situation can follow with casualties from injured patients. For this reason, an appropriate set up for these cases is formulated. Last, the staging of a hospital before feasible contingences is proposed and the experience of the events of the 9/19 earthquake disaster retaken for this purpose.

Can CT and MR Shape and Textural Features Differentiate Benign Versus Malignant Pleural Lesions?

RATIONALE AND OBJECTIVES: The study aimed to identify a radiomic approach based on CT and or magnetic resonance (MR) features (shape and texture) that may help differentiate benign versus malignant pleural lesions, and to assess if the radiomic model may improve confidence and accuracy of radiologists with different subspecialty backgrounds. MATERIALS AND METHODS: Twenty-nine patients with pleural lesions studied on both contrast-enhanced CT and MR imaging were reviewed retrospectively. Three texture and three shape features were extracted. Combinations of features were used to generate logistic regression models using histopathology as outcome. Two thoracic and two abdominal radiologists evaluated their degree of confidence in malignancy. Diagnostic accuracy of radiologists was determined using contingency tables. Cohen's kappa coefficient was used to assess inter-reader agreement. Using optimal threshold criteria, sensitivity, specificity, and accuracy of each feature and combination of features were obtained and compared to the accuracy and confidence of radiologists. RESULTS: The CT model that best discriminated malignant from benign lesions revealed an AUCCT = 0.92 ± 0.05 (P < 0.0001). The most discriminative MR model showed an AUCMR = 0.87 ± 0.09 (P < 0.0001). The CT model was compared to the diagnostic confidence of all radiologists and the model outperformed both abdominal radiologists (P < 0.002), whereas the top discriminative MR model outperformed one of the abdominal radiologists (P = 0.02). The most discriminative MR model was more accurate than one abdominal (P = 0.04) and one thoracic radiologist (P = 0.02). CONCLUSION: Quantitative textural and shape analysis may help distinguish malignant from benign lesions. A radiomics-based approach may increase diagnostic confidence of abdominal radiologists on CT and MR and may potentially improve radiologists' accuracy in the assessment of pleural lesions characterized by MR.

Anomalous Coronary Arteries That Need Intervention: Review of Pre- and Postoperative Imaging Appearances.

Coronary artery anomalies constitute a diverse group of abnormalities, ranging from anatomic variants to those having hemodynamic consequences. This review focuses on major anomalies that have clinical implications requiring treatment, including anomalous origin of the coronary artery from the opposite sinus with interarterial course specifically with an intramural course, coronary artery origin from the pulmonary artery, and coronary artery fistula. Comprehensive imaging evaluation is necessary to precisely delineate the anatomy as well as pathophysiologic aspects of the anomaly before determining treatment options for a specific patient. Coronary computed tomographic angiography provides elegant depiction of coronary arterial anatomy and the relationship of the vessel to the adjacent structures, with the ability to perform three-dimensional reconstructions. Magnetic resonance (MR) imaging is emerging as an alternative noninvasive imaging strategy, particularly in young individuals, due to the lack of ionizing radiation and avoidance of iodinated contrast agents. This review describes the roles and recent technical advancements in computed tomography and MR imaging pertinent to coronary artery imaging. Additionally, this article will familiarize readers with the cross-sectional imaging appearance of clinically relevant coronary anomalies, hemodynamic considerations, and complex decision making. The different management strategies used for these anomalies, such as coronary unroofing, reimplantation, bypass grafting, Takeuchi repair, and surgical and interventional closure of fistulas, as well as specific posttreatment complications, are also discussed. ©RSNA, 2017.

Lower serum magnesium is associated with vascular calcification in peritoneal dialysis patients: a cross sectional study.

BACKGROUND: Coronary artery calcification (CAC) is highly prevalent among dialysis patients and is associated with increased cardiovascular and all cause mortality. Magnesium (Mg) inhibits vascular calcification in animal and in-vitro studies but whether the same effect occurs in humans is uncertain. METHODS: A single centre cross-sectional study of 80 prevalent peritoneal dialysis (PD) patients; on PD only for a minimum of 3 months. A radiologist blinded to patient status calculated their abdominal aortic calcification (AAC) scores on lateral lumbar spine radiographs, a validated surrogate for CAC. RESULTS: Eighty patients provided informed consent and underwent lumbar spine radiography. The mean serum Mg was 0.8 mmol/L (standard deviation 0.2) and mean AAC score 8.9 (minimum 0, maximum 24). A higher serum Mg level was associated with a lower AAC score (R 2 = 0.06, unstandardized coefficient [B] = -7.81, p = 0.03), and remained after adjustment for age, serum phosphate, serum parathyroid hormone, low-density lipoprotein cholesterol, smoking history, and diabetes (model adjusted R 2 = 0.36, serum Mg and AAC score B = -11.44, p = 0.00). This translates to a 0.1 mmol/L increase in serum Mg being independently associated with a 1.1-point decrease in AAC score. CONCLUSIONS: Our findings suggest that Mg may inhibit vascular calcification. If this association is replicated across larger studies with serial Mg and vascular calcification measurements, interventions that increase serum Mg and their effect on vascular calcification warrant further investigation in the PD population.

Allicin Induces Calcium and Mitochondrial Dysregulation Causing Necrotic Death in Leishmania.

BACKGROUND: Allicin has shown antileishmanial activity in vitro and in vivo. However the mechanism of action underlying its antiproliferative effect against Leishmania has been virtually unexplored. In this paper, we present the results obtained in L.infantum and a mechanistic basis is proposed. METHODOLOGY/PRINCIPAL FINDING: Exposure of the parasites to allicin led to high Ca2+ levels and mitochondrial reactive oxygen species (ROS), collapse of the mitochondrial membrane potential, reduced production of ATP and elevation of cytosolic ROS. The incubation of the promastigotes with SYTOX Green revealed that decrease of ATP was not associated with plasma membrane permeabilization. Annexin V and propidium iodide (PI) staining indicated that allicin did not induce phospholipids exposure on the plasma membrane. Moreover, DNA agarose gel electrophoresis and TUNEL analysis demonstrated that allicin did not provoke DNA fragmentation. Analysis of the cell cycle with PI staining showed that allicin induced cell cycle arrest in the G2/M phase. CONCLUSIONS/SIGNIFICANCE: We conclude that allicin induces dysregulation of calcium homeostasis and oxidative stress, uncontrolled by the antioxidant defense of the cell, which leads to mitochondrial dysfunction and a bioenergetic catastrophe leading to cell necrosis and cell cycle arrest in the premitotic phase.

Fat embolism syndrome: State-of-the-art review focused on pulmonary imaging findings.

BACKGROUND: Fat embolism syndrome (FES) is a rare but potentially fatal complication of trauma or orthopedic surgery, which presents predominantly with pulmonary symptoms. Modern intensive care has improved the mortality rates, however diagnosis remains difficult, relying predominantly on a combination of a classic triad of symptoms and non-specific, but characteristic radiological features. The aim of this review is to describe the main clinical and imaging aspects of FES, ranging from pathophysiology to treatment with emphasis on pulmonary involvement. METHODS: We reviewed the currently published literature on the main characteristics of FES. RESULTS: In a hypoxic patient with recent trauma or orthopedic surgery, the presence of diffuse, well-demarcated ground glass opacities or ill-defined centrilobular nodules on computed tomography (CT) of the chest are suggestive of FES. CONCLUSIONS: Combination of the classic clinical syndrome in the appropriate clinical setting, together with the characteristic imaging findings on chest CT, can help to achieve the correct diagnosis. Management remains predominantly supportive care, and the benefit of medical therapies such as corticosteroids and heparin remains unclear.

Fat embolism syndrome: Do the CT findings correlate with clinical course and severity of symptoms? A clinical-radiological study.

OBJECTIVE: Fat embolism syndrome (FES) is rare and diagnosis is challenging. Clinical manifestations are non-specific and no biochemical tests are reliable for diagnosis, highlighting the importance of thoracic CT. Our goal was to describe the CT manifestations of FES and assess whether imaging findings, time of onset of symptoms and time of surgery correlate with clinical course and severity of the disease. METHODS: Retrospective review of 49 patients with respiratory distress after trauma/intramedullary nail fixation over a 10 year period; 12 patients met clinical criteria and were categorized as non-fulminant (NF-FES) or fulminant FES (F-FES). CT images were analyzed and electronic records reviewed for clinical findings, timeline from trauma to surgery and onset of symptoms. Pearson Chi-square and Levene's test were used and results considered significant when p<0.05. RESULTS: All patients were men (18-80 years, mean 38 years), 5 (42%) suffered F-FES and 7 (58%) NF-FES. The most common CT finding was ground-glass opacities (8/12, 67%), often with lobular sparing. Consolidation occurred in 4/12 (33%), all in F-FES patients (p=0.004). In 5/5 F-FES, lung involvement was extensive (>75%) whereas most NF-FES had limited involvement (p<0.01). Centrilobular nodules were the predominant finding in 3/12 (16%). Median time between fracture and onset of symptoms was 43h, in 9/12 patients manifesting after surgery. Mean time between trauma and surgery was 20h in NF-FES and 52h in F-FES (p=0.02). CONCLUSIONS: The most common CT features of FES were ground-glass opacity and consolidation, less commonly, centrilobular nodules. The extent of ground-glass opacities and the presence of consolidation correlated with disease severity. Significant difference was found from time of trauma to surgery in the two groups however is uncertain whether delayed surgery truly increased the risk of F-FES.