Publications by authors named "Sara Campos"

62 Publications

Curriculum for ERCP and endoscopic ultrasound training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

Endoscopy 2021 10 26;53(10):1071-1087. Epub 2021 Jul 26.

Department of Gastroenterology and Hepatology, University Hospitals Leuven, and TARGID, KU Leuven, Leuven, Belgium.

The European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize and enhance training in endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS). This manuscript represents the outcome of a formal Delphi process resulting in an official Position Statement of the ESGE and provides a framework to develop and maintain skills in ERCP and EUS. This curriculum is set out in terms of the prerequisites prior to training; recommended steps of training to a defined syllabus; the quality of training; and how competence should be defined and evidenced before independent practice. 1: Trainees should be competent in gastroscopy prior to commencing training. Formal training courses and the use of simulation in training are recommended. 2: Trainees should keep a contemporaneous logbook of their procedures, including key performance indicators and the degree of independence. Structured formative assessment is encouraged to enhance feedback. There should be a summative assessment process prior to commencing independent practice to ensure there is robust evidence of competence. This evidence should include a review of a trainee's procedure volume and current performance measures. A period of mentoring is strongly recommended in the early stages of independent practice. 3: Specifically for ERCP, all trainees should be competent up to Schutz level 2 complexity (management of distal biliary strictures and stones > 10 mm), with advanced ERCP requiring a further period of training. Prior to independent practice, ESGE recommends that a trainee can evidence a procedure volume of > 300 cases, a native papilla cannulation rate of ≥ 80 % (90 % after a period of mentored independent practice), complete stones clearance of ≥ 85 %, and successful stenting of distal biliary strictures of ≥ 90 % (90 % and 95 % respectively after a mentored period of independent practice). 4: The progression of EUS training and competence attainment should start from diagnostic EUS and then proceed to basic therapeutic EUS, and finally to advanced therapeutic EUS. Before independent practice, ESGE recommends that a trainee can evidence a procedure volume of > 250 cases (75 fine-needle aspirations/biopsies [FNA/FNBs]), satisfactory visualization of key anatomical landmarks in ≥ 90 % of cases, and an FNA/FNB accuracy rate of ≥ 85 %. ESGE recognizes the often inadequate quality of the evidence and the need for further studies pertaining to training in advanced endoscopy, particularly in relation to therapeutic EUS.
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http://dx.doi.org/10.1055/a-1537-8999DOI Listing
October 2021

Effect of pH on the influenza fusion peptide properties unveiled by constant-pH molecular dynamics simulations combined with experiment.

Sci Rep 2020 11 18;10(1):20082. Epub 2020 Nov 18.

ITQB NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157, Oeiras, Portugal.

The influenza virus fusion process, whereby the virus fuses its envelope with the host endosome membrane to release the genetic material, takes place in the acidic late endosome environment. Acidification triggers a large conformational change in the fusion protein, hemagglutinin (HA), which enables the insertion of the N-terminal region of the HA2 subunit, known as the fusion peptide, into the membrane of the host endosome. However, the mechanism by which pH modulates the molecular properties of the fusion peptide remains unclear. To answer this question, we performed the first constant-pH molecular dynamics simulations of the influenza fusion peptide in a membrane, extending for 40 µs of aggregated time. The simulations were combined with spectroscopic data, which showed that the peptide is twofold more active in promoting lipid mixing of model membranes at pH 5 than at pH 7.4. The realistic treatment of protonation introduced by the constant-pH molecular dynamics simulations revealed that low pH stabilizes a vertical membrane-spanning conformation and leads to more frequent contacts between the fusion peptide and the lipid headgroups, which may explain the increase in activity. The study also revealed that the N-terminal region is determinant for the peptide's effect on the membrane.
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http://dx.doi.org/10.1038/s41598-020-77040-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674464PMC
November 2020

High Cysteine Membrane Proteins (HCMPs) Are Up-Regulated During -Host Cell Interactions.

Front Genet 2020 18;11:913. Epub 2020 Aug 18.

Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.

colonizes the upper small intestine of humans and animals, causing the diarrheal disease giardiasis. This unicellular eukaryotic parasite is not invasive but it attaches to the surface of small intestinal epithelial cells (IECs), disrupting the epithelial barrier. Here, we used an model of the parasite's interaction with host IECs (differentiated Caco-2 cells) and RNA sequencing (RNAseq) to identify differentially expressed genes (DEGs) in , which might relate to the establishment of infection and disease induction. trophozoites interacted with differentiated Caco-2 cells for 1.5, 3, and 4.5 h and at each time point, 61, 89, and 148 parasite genes were up-regulated more than twofold, whereas 209, 265, and 313 parasite genes were down-regulated more than twofold. The most abundant DEGs encode hypothetical proteins and members of the High Cysteine Membrane Protein (HCMP) family. Among the up-regulated genes we also observed proteins associated with proteolysis, cellular redox balance, as well as lipid and nucleic acid metabolic pathways. In contrast, genes encoding kinases, regulators of the cell cycle and arginine metabolism and cytoskeletal proteins were down-regulated. Immunofluorescence imaging of selected, up-regulated HCMPs, using C-terminal HA-tagging, showed localization to the plasma membrane and peripheral vesicles (PVs). The expression of the HCMPs was affected by histone acetylation and free iron-levels. In fact, the latter was shown to regulate the expression of many putative giardial virulence factors in subsequent RNAseq experiments. We suggest that the plasma membrane localized and differentially expressed HCMPs play important roles during -host cell interactions.
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http://dx.doi.org/10.3389/fgene.2020.00913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461913PMC
August 2020

Endoprotector: Protective box for safe endoscopy use during COVID-19 outbreak.

Endosc Int Open 2020 Jun 2;8(6):E817-E821. Epub 2020 Jun 2.

Gastroenterology Department, Hospital Garcia de Orta, Portugal.

 Outbreak of COVID-19 began in Wuhan in December 2019 and has rapidly spread from China to the rest of the world. Although it is primarily transmitted by contact and droplets, aerosol-generating procedures also seem to carry the possibility of airborne viral transmission. As such, upper gastrointestinal endoscopy can be considered a risky procedure, with several position statements recommending the adoption of safe practices in endoscopic procedures. This article aims to describe an additional tool to protect healthcare personnel during endoscopy.  A covering box made of acrylic plastic, named Endoprotector, was designed to cover the patient's head, while taking into consideration movements performed by patients and healthcare staff during an endoscopic procedure.  A cough simulation using fluorescent dye confirmed the potential benefit of the box during endoscopy, thus protecting healthcare staff from air droplets. The feasibility and practicality of the box was also tested with patients during endoscopy.  The reusable Endoprotector is easily and affordably manufactured and may reduce air droplets and airborne transmission of SARS-CoV-2 and other microorganisms during endoscopy.
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http://dx.doi.org/10.1055/a-1180-8527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266658PMC
June 2020

Biomarker-guided implementation of the KDIGO guidelines to reduce the occurrence of acute kidney injury in patients after cardiac surgery (PrevAKI-multicentre): protocol for a multicentre, observational study followed by randomised controlled feasibility trial.

BMJ Open 2020 04 6;10(4):e034201. Epub 2020 Apr 6.

Anesthesiology, Intensive Care and Pain Medicine, Universitatsklinikum Munster, Munster, Nordrhein-Westfalen, Germany

Introduction: Acute kidney injury (AKI) is a frequent complication after cardiac surgery with adverse short-term and long-term outcomes. Although prevention of AKI (PrevAKI) is strongly recommended, the optimal strategy is uncertain. The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommended a bundle of supportive measures in high-risk patients. In a single-centre trial, we recently demonstrated that the strict implementation of the KDIGO bundle significantly reduced the occurrence of AKI after cardiac surgery. In this feasibility study, we aim to evaluate whether the study protocol can be implemented in a multicentre setting in preparation for a large multicentre trial.

Methods And Analysis: We plan to conduct a prospective, observational survey followed by a randomised controlled, multicentre, multinational clinical trial including 280 patients undergoing cardiac surgery with cardiopulmonary bypass. The purpose of the observational survey is to explore the adherence to the KDIGO recommendations in routine clinical practice. The second phase is a randomised controlled trial. The objective is to investigate whether the trial protocol is implementable in a large multicentre, multinational setting. The primary endpoint of the interventional part is the compliance rate with the protocol. Secondary endpoints include the occurrence of any AKI and moderate/severe AKI as defined by the KDIGO criteria within 72 hours after surgery, renal recovery at day 90, use of renal replacement therapy (RRT) and mortality at days 30, 60 and 90, the combined endpoint major adverse kidney events consisting of persistent renal dysfunction, RRT and mortality at day 90 and safety outcomes.

Ethics And Dissemination: The PrevAKI multicentre study has been approved by the leading Research Ethics Committee of the University of Münster and the respective Research Ethics Committee at each participating site. The results will be used to design a large, definitive trial.

Trial Registration Number: NCT03244514.
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http://dx.doi.org/10.1136/bmjopen-2019-034201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245412PMC
April 2020

Methods and outcome of the endoscopic treatment of ampullary tumors.

Ther Adv Gastrointest Endosc 2020 Jan-Dec;13:2631774519899786. Epub 2020 Jan 21.

Gastroenterology & Hepatology, Erasmus MC, Rotterdam, The Netherlands.

Ampullary tumors are rare neoplasms but increasingly encountered due to an increase in diagnostic procedures, mainly upper gastrointestinal endoscopy. Diagnosis, staging, and treatment of these tumors are described and recommendations given based on the most recent literature.
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http://dx.doi.org/10.1177/2631774519899786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977234PMC
January 2020

A Multinational Observational Study Exploring Adherence With the Kidney Disease: Improving Global Outcomes Recommendations for Prevention of Acute Kidney Injury After Cardiac Surgery.

Anesth Analg 2020 04;130(4):910-916

From the Department of Anaesthesiology, Intensive Care Medicine and Pain Medicine, University Hospital Münster, Münster, Germany.

Background: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a bundle of different measures for patients at increased risk of acute kidney injury (AKI). Prospective, single-center, randomized controlled trials (RCTs) have shown that management in accordance with the KDIGO recommendations was associated with a significant reduction in the incidence of postoperative AKI in high-risk patients. However, compliance with the KDIGO bundle in routine clinical practice is unknown.

Methods: This observational prevalence study was performed in conjunction with a prospective RCT investigating the role of the KDIGO bundle in high-risk patients undergoing cardiac surgery. A 2-day observational prevalence study was performed in all participating centers before the RCT to explore routine clinical practice. The participating hospitals provided the following data: demographics and surgical characteristics, AKI rates, and compliance rates with the individual components of the bundle.

Results: Ninety-five patients were enrolled in 12 participating hospitals. The incidence of AKI within 72 hours after cardiac surgery was 24.2%. In 5.3% of all patients, clinical management was fully compliant with all 6 components of the bundle. Nephrotoxic drugs were discontinued in 52.6% of patients, volume optimization was performed in 70.5%, 52.6% of the patients underwent functional hemodynamic monitoring, close monitoring of serum creatinine and urine output was undertaken in 24.2% of patients, hyperglycemia was avoided in 41.1% of patients, and no patient received radiocontrast agents. The patients received on average 3.4 (standard deviation [SD] ±1.1) of 6 supportive measures as recommended by the KDIGO guidelines. There was no significant difference in the number of applied measures between AKI and non-AKI patients (3.2 [SD ±1.1] vs 3.5 [SD ±1.1]; P = .347).

Conclusions: In patients after cardiac surgery, compliance with the KDIGO recommendations was low in routine clinical practice.
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http://dx.doi.org/10.1213/ANE.0000000000004642DOI Listing
April 2020

The role of EUS in diagnosis and treatment of liver disorders.

Endosc Int Open 2019 Oct 1;7(10):E1262-E1275. Epub 2019 Oct 1.

Department of Gastroenterology and Hepatology, Erasmus MC, The Netherlands.

 Transabdominal ultrasound (US), computed tomographic scanning (CT) and magnetic resonance imaging (MRI) are established diagnostic tools for liver diseases. Percutaneous transhepatic cholangiography is used to perform hepatic interventional procedures including biopsy, biliary drainage procedures, and radiofrequency ablation. Despite their widespread use, these techniques have limitations. Endoscopic ultrasound (EUS), a tool that has proven useful for evaluating the mediastinum, esophagus, stomach, pancreas, and biliary tract, has an expanding role in the field of hepatology complementing the traditional investigational modalities. This review aimed to assess the current scientific evidence regarding diagnostic and therapeutic applications of EUS for hepatic diseases.
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http://dx.doi.org/10.1055/a-0958-2183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773586PMC
October 2019

Defining the Minimum Acceptable Diagnostic Accuracy of Noninvasive Fibrosis Testing in Cirrhosis: A Decision Analytic Modeling Study.

Hepatology 2020 02 19;71(2):627-642. Epub 2019 Aug 19.

UCL Institute for Liver and Digestive Health, Royal Free Hospital and University College London, London, UK.

No studies explore the clinical consequences of using noninvasive tests (NITs) compared to liver biopsy (LB) in diagnosing cirrhosis. Our aim was to combine two decision analytic models to determine the minimum diagnostic accuracy criteria for NITs to diagnose cirrhosis with equivalence to LB in terms of mortality. We further evaluated selected existing NITs used alone and sequentially. A decision tree was constructed with associated 2-year mortality incorporating an LB or NIT strategy to diagnose cirrhosis in a hypothetical cohort of 1,000 asymptomatic patients. Cirrhosis prevalence was modeled at 5%, 20%, and 50%. Decision curve analyses were performed, expressing the net benefit of tests over a range of threshold probabilities (P ). The NIT deriving from the two models that could diagnose cirrhosis with at least equal mortality to LB was termed "mNIT." Existing NITs were then compared using both decision models. The combined mNIT minimum sensitivity and specificity to diagnose cirrhosis with equivalence to LB at 5%, 20% and 50% cirrhosis prevalence were; 89% and 88%, 94% and 85%, and 94% and 87%, respectively at P  = 0.20. Sequential NITs performed better than single NITs at any prevalence. Combining both decision models, FibroTest plus vibration-controlled transient elastography (VCTE) and VCTE alone were the only existing NITs that were better than or equal to LB at diagnosing cirrhosis at 5% prevalence. At 20% and 50% prevalence, only FibroTest high specificity cutoff plus VCTE was equivalent to or better than LB. Conclusion: Decision analytic models were used to determine the minimum acceptable diagnostic accuracy of NITs for diagnosing cirrhosis; we recommend that such models should be used as the standard in evaluating the diagnostic performance of NITs.
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http://dx.doi.org/10.1002/hep.30846DOI Listing
February 2020

Molecular Anatomy of Plant Photoprotective Switches: The Sensitivity of PsbS to the Environment, Residue by Residue.

J Phys Chem Lett 2019 Apr 29;10(8):1737-1742. Epub 2019 Mar 29.

Department of Physics and Astronomy, Faculty of Sciences , Vrije Universiteit Amsterdam , De Boelelaan 1081 , 1081 HV Amsterdam , The Netherlands.

Under strong sunlight, plants avoid photooxidation by quenching the excess absorbed energy. Quenching is triggered by PsbS, a membrane protein that is activated and deactivated by the light-dependent pH changes in the thylakoid lumen. The mechanism of action of this protein is unknown, but it was suggested that several glutamates act as pH sensors. However, the p K of glutamate is several pH units below the physiological values in the lumen. Thus, how can PsbS sense the pH of the lumen, and how does it respond to it? By applying a nonstandard molecular dynamics method that treats pH explicitly, we show that the lumen-exposed glutamates of PsbS have strongly shifted p K values and that such shifts are crucial for the pH sensitivity in physiological conditions. We also demonstrate that protonation drives a systematic unfolding of a region key for protein-protein interactions, indicating that PsbS response to pH is a functional conformational switch.
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http://dx.doi.org/10.1021/acs.jpclett.9b00437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477805PMC
April 2019

A [Glyco]biomarker that Predicts Failure to Standard Therapy in Ulcerative Colitis Patients.

J Crohns Colitis 2019 Jan;13(1):39-49

Institute of Molecular Pathology and Immunology of the University of Porto [IPATIMUP], Porto, Portugal.

Background And Aims: There is a clinical need to identify biomarkers able to select patients who are most likely to develop aggressive/complicated disease, for early selection for appropriate therapy. Changes in the glycosylation profile of intestinal lymphocytic infiltrate were previously demonstrated to regulate T cell activity, being associated with disease severity in ulcerative colitis [UC] patients. We interrogated whether this heterogeneous expression of branched N-glycans in intestinal inflammatory infiltrate predicts therapy response early in disease course.

Methods: The expression levels of the branched N-glycans in colonic biopsies collected around time of diagnosis from a well-characterised cohort of 131 UC patients were correlated with response to standard therapy. Receiver operating characteristic analysis and specificity/sensitivity were determined.

Results: Branched N-glycans levels around time of diagnosis predict non-response to conventional therapy with 75% specificity. Moreover, high levels of branched N-glycans predict 78% of UC patients who will display a favourable disease course [exclusively under 5-aminosalicylate therapy for more than 5 years of disease]. The best predictive performance was observed in severe UC patients with Mayo endoscopic subscore 3 and in those that were naïve to therapy. Multivariable analysis revealed that low levels of branched N-glycans and high levels of C-reactive protein [CRP] around time of diagnosis act as independent predictors of non-response to standard therapy. A powerful effect of the combined use of the branched N-glycans and CRP was observed.

Conclusions: Our results reveal a potential [glyco]biomarker that predicts, early in the disease course, patients who will fail to respond to standard therapy, benefiting thereby from other therapeutic strategies such as biologics.
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http://dx.doi.org/10.1093/ecco-jcc/jjy139DOI Listing
January 2019

Role of Counterions in Constant-pH Molecular Dynamics Simulations of PAMAM Dendrimers.

ACS Omega 2018 Feb 19;3(2):2001-2009. Epub 2018 Feb 19.

Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal.

Electrostatic interactions play a pivotal role in the structure and mechanism of action of most biomolecules. There are several conceptually different methods to deal with electrostatics in molecular dynamics simulations. Ionic strength effects are usually introduced using such methodologies and can have a significant impact on the quality of the final conformation space obtained. We have previously shown that full system neutralization can lead to wrong lipidic phases in the 25% PA/PC bilayer (. 5483-5492). In this work, we investigate how two limit approaches to the ionic strength treatment (implicitly with GRF or using full system neutralization with either GRF or PME) can influence the conformational space of the second-generation PAMAM dendrimer. Constant-pH MD simulations were used to map PAMAM's conformational space at its full pH range (from 2.5 to 12.5). Our simulations clearly captured the coupling between protonation and conformation in PAMAM. Interestingly, the dendrimer conformational distribution was almost independent of the ionic strength treatment methods, which is in contrast to what we have observed in charged lipid bilayers. Overall, our results confirm that both GRF with implicit ionic strength and a fully neutralized system with PME are valid approaches to model charged globular systems, using the GROMOS 54A7 force field.
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http://dx.doi.org/10.1021/acsomega.7b01708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045380PMC
February 2018

Ulcerative Colitis: Are We Neglecting Its Progressive Character.

GE Port J Gastroenterol 2018 Mar 20;25(2):74-79. Epub 2017 Oct 20.

Department of Gastroenterology, Centro Hospitalar e Universitário de Coimbra, EPE, Coimbra, Portugal.

Introduction: Ulcerative colitis (UC) is a chronic disease but its progressive character, with structural damage, is insufficiently studied.

Objectives: To analyze a group of patients without referral bias, regarding its clinical course, the morphological damage, and functional status.

Methods: We evaluated UC patients diagnosed between January 1, 2000 and December 31, 2004, living in the direct referral area of the hospital and determined the medication use, colectomy rate, structural damage ("lead pipe," stenosis, pseudopolyps, fibrous bridges), and anorectal function (prospective evaluation with the Cleveland Clinic Incontinence Score [CCIS] and the Fecal Incontinence Quality of Life Scale).

Results: We identified 104 patients, 47% female, with a mean age at diagnosis of 38 ± 17 years, 24% with proctitis, 57% with left colitis, and 19% with pancolitis. In 3 patients, it was not possible to obtain follow-up data. Of the studied patients, 56% needed corticosteroid therapy, 38% immunosuppressants, and 16% anti-tumor necrosis factors (anti-TNFs). After a mean follow-up of 13 ± 2 years, we found structural damage in 25 patients (24%): 5% with proctocolectomy, 15% with "lead pipe," 16% with pseudopolyps, and 3% with stenosis and fibrous bridges. Reference to functional anorectal disorders was identified in 49%, mostly previous and self-limited episodes of incontinence, but including persistent incontinence in 10% (CCIS 8 ± 4.8). There was an increased incidence of structural damage and anorectal dysfunction in patients who needed corticosteroid therapy ( = 0.001), immunosuppressants ( < 0.001), and anti-TNFs ( = 0.002) and an association of structural damage with anorectal dysfunction ( < 0.001). There was no association between age and anorectal dysfunction, including incontinence episodes.

Conclusions: UC is a disease with structural and functional consequences in a significant subset of patients. This should be incorporated when defining the therapeutic strategy.
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http://dx.doi.org/10.1159/000481263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892362PMC
March 2018

Mucosal and Periungual Telangiectasia as Signs of Systemic Disease.

Acta Med Port 2018 Feb 28;31(2):133. Epub 2018 Feb 28.

Dermatology and Venereology Department. Hospital Santo António dos Capuchos. Centro Hospitalar de Lisboa Central. Lisboa. Portugal.

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http://dx.doi.org/10.20344/amp.10307DOI Listing
February 2018

Lichen planus pemphigoides.

J Dtsch Dermatol Ges 2018 Mar;16(3):335-337

Department of Dermatology and Venereology, Centro Hospitalar de Lisboa Central, Lisbon, Portugal.

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http://dx.doi.org/10.1111/ddg.13434_gDOI Listing
March 2018

Lichen planus pemphigoides.

J Dtsch Dermatol Ges 2018 Mar 21;16(3):335-337. Epub 2018 Feb 21.

Department of Dermatology and Venereology, Centro Hospitalar de Lisboa Central, Lisbon, Portugal.

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http://dx.doi.org/10.1111/ddg.13434DOI Listing
March 2018

[Retroperitoneal Cellular Angiofibroma: A Rare Gynecological Entity].

Acta Med Port 2017 Dec 29;30(12):882-886. Epub 2017 Dec 29.

Serviço de Ginecologia A. Centro Hospitalar e Universitário de Coimbra. Coimbra. Portugal.

Cellular angiofibroma is a mesenchymal tumor, described in 1997, without gender preference, that usually appears at age 40. The vulvovaginal area is the most common site in women, mimicking vulvar benign tumors, like Bartholin gland cyst. However, there are a few described cases of a deep or extra-pelvic angiofibroma. Excision is the treatment of choice and the recurrence rate appears to be low. We present the case of a woman with a heterogeneous tumor in the right adnexial region. At the surgery, a retroperitoneal tumor was excised and the histopathological tissue analysis revealed a cellular angiofibroma.
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http://dx.doi.org/10.20344/amp.8774DOI Listing
December 2017

Metastatic Crohn's disease despite infliximab therapy.

An Bras Dermatol 2017 ;92(5 Suppl 1):104-106

Department of Gastroenterology at Centro Hospitalar e Universitário de Coimbra (Chuc) - Coimbra, Portugal.

Metastatic Crohn's disease is a rare extraintestinal manifestation of Crohn's disease. It is characterized by polymorphic skin lesions formed by non-caseating granulomas located on anatomical sites distant from the gastrointestinal tract. We report a rare case of metastatic Crohn's disease, simultaneously displaying multiple clinically heterogeneous cutaneous lesions, in a patient with previously diagnosed Crohn's disease in remission due to anti-TNF-α use. This case highlights the need for high clinical suspicion and early biopsy in the setting of a patient with Crohn's disease and persistent skin lesions, even under biologic therapy. Furthermore, it reinforces the need of monitoring of the serum level of infliximab, increasing the dose in case it is low or undetectable.
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http://dx.doi.org/10.1590/abd1806-4841.20175713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726693PMC
March 2018

Uncertainties in the Management of a Lynch Syndrome Patient: A Case Report.

GE Port J Gastroenterol 2017 Sep 23;24(5):241-246. Epub 2017 Mar 23.

Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

Introduction: Lynch syndrome (LS), the most common hereditary colorectal cancer syndrome, is characterized by mutations in mismatch repair (MMR) genes leading to an increased cancer risk, namely colorectal cancer.

Case: In the context of surveillance colonoscopy, a 40-mm flat lesion (0-IIa+b, Paris classification) was identified and submitted to piecemeal mucosal endoscopic resection in a 64-year-old LS patient with an MLH1 germline mutation (262delATC) and two previous segmental resections due to metachronous colorectal cancer. Pathology raised the suspicion of superficial submucosal invasive carcinoma with poor differentiation. Immunochemistry showed heterogeneous MLH1 expression and PMS2 loss. In a short-term follow-up colonoscopy, another 30-mm advanced carcinoma was identified. The patient was referred to surgery.

Conclusion: This case raises several issues: (1) the potentially fast tumorigenesis and progression to carcinoma in LS and implications for endoscopic screening and surveillance; (2) pitfalls in the interpretation of MMR proteins immunochemistry; (3) the role of endoscopic resection in LS.
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http://dx.doi.org/10.1159/000461590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729953PMC
September 2017

Vitamin D levels in a cohort of Portuguese melanoma patients relate to time of follow-up from diagnosis, sun-exposure behaviour, and use of photoprotection.

Eur J Dermatol 2018 02;28(1):93-94

Dermatology and Venereology Department, Hospital de Santo António dos Capuchos - Centro Hospitalar de Lisboa Central, Alameda de Santo António dos Capuchos, 1169-050 Lisboa, Portugal.

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http://dx.doi.org/10.1684/ejd.2017.3161DOI Listing
February 2018

Chronic leg ulcers disrupt patients' lives: A study of leg ulcer-related life changes and quality of life.

Br J Community Nurs 2017 Sep;22(Sup9):S30-S37

Dermatology Department, Hospital de Santo António dos Capuchos - Centro Hospitalar de Lisboa Central, Portugal.

Chronic leg ulcers have a profound impact on patients' physical, functional, and psychological status, which may result in several life changes and a significant decline in quality of life (QoL). We aimed to study what changed in patients' lives after developing a chronic leg ulcer, including QoL, patients' comprehension of the disease and related feelings. A cross-sectional study, using an anonymous questionnaire and the Dermatology Life Quality Index (DLQI) was performed. Chronic leg ulcers were life changing events, causing abandonment of work in almost 80% of the patients and important limitations in daily activities and autonomy. Familial relationships changed in more than half of the patients. Almost 15% hid or would like to hide their disease from others, especially patients with a shorter duration of disease. QoL was very or extremely affected in 18.2% of the participants completing the DLQI.
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http://dx.doi.org/10.12968/bjcn.2017.22.Sup9.S30DOI Listing
September 2017

sQuiz your knowledge: Nipple ulceration.

Eur J Dermatol 2017 Jun;27(3):339-340

Serviço de Dermatologia, Centro Hospitalar Lisboa Central, Lisboa, Portugal.

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http://dx.doi.org/10.1684/ejd.2017.3057DOI Listing
June 2017

sQuiz your knowledge: Expanding scarring alopecia in a patient with porphyria cutanea tarda.

Eur J Dermatol 2017 Apr;27(2):222-223

Centro Hospitalar Lisboa Central, Hospital dos Capuchos-Dermatology, Alameda Santo António dos Capuchos, 1169 Lisbon, Portugal.

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http://dx.doi.org/10.1684/ejd.2017.3005DOI Listing
April 2017

The clinical extremes of autoimmune cholangitis.

Rev Esp Enferm Dig 2017 Jun;109(6):465-468

Gastroenterology, Centro Hospitalar e Universitário de Coimbra.

Autoimmune cholangitis (AIC) was first described in 1987 as immunocholangitis in three women who presented with signs and symptoms of primary biliary cholangitis (PBC), but who were antimitochondrial (AMA) negative and antinuclear antibodies (ANA) positive, and responded to immunosuppressive therapy with azathioprine and prednisolone (1). AIC is a rare chronic cholestatic inflammatory disease characterized by the presence of high ANA or smooth muscle antibodies (SMA) but AMA seronegativity. Histologically, AIC exhibits bile duct injury (2). In terms of therapeutics, in addition to response to ursodeoxycholic acid, a prompt response to corticosteroids has also been reported in earlier stages, distinguishing it from PBC. Herein the authors describe two cases with mixed signs of PBC and autoimmune hepatitis (AIH). The diagnostic differentiation between these diseases (AIC, PBC and AIH) is essential because of the different therapeutic strategies. Our cases highlight the importance of clinician awareness of the autoimmune spectrum of liver diseases.
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http://dx.doi.org/10.17235/reed.2017.4167/2015DOI Listing
June 2017

POEMS syndrome and idiopathic portal hypertension: a possible association.

Rev Esp Enferm Dig 2017 May;109(5):393

Pathology, Centro Hospitalar e Universitário de Coimbra.

A 48-year old female patient was admitted to the emergency department with upper gastrointestinal bleeding. Endoscopy showed large esophageal varices that were treated with band ligation. She had been treated with cyclophosphamide, melphalan, lenalidomide and corticosteroids for POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy or edema, M protein, skin changes). She had no other risk factors for chronic liver disease. Laboratory and radiological examinations could not confirm the etiology of portal hypertension. The liver biopsy suggested hepatoportal sclerosis, compatible with idiopathic portal hypertension (IPH). Under a band ligation program, with beta-blocker, diuretics and prophylactic anticoagulation, the patient remains stable. In POEMS syndrome, a rare multi-systemic disease, the most frequent liver manifestation is hepatomegaly(1). To the best of authors' knowledge, IPH has been reported only 3 times in POEMS syndrome(2,3,4) and this is the second case reporting the occurrence of histological findings compatible with IPH. As the precise etiopathogenesis of IPH is not fully elucidated and as it is an extremely uncommon manifestation in POEMS, it is not yet certain whether IPH is part of the syndrome or whether it develops independently. While some investigators believe that there is a congenital vascular anomaly involving the changes in the portal tract, the majority support an acquired vascular defect hypothesis(5). The acquired IPH hypothesis emphasizes a possible role of various pathogenic determinants: infections, prothrombotic states, prolonged exposure to several medications and toxins, immunological basis and progressive fibrosis of the portal veins (5). In this hypothesis, a hepatic circulation defect secondary to POEMS syndrome, which includes pro-inflammatory (VEGF, interleukin (IL)-6, IL-1ß, tumor necrosis factor-α, tumor growth factor-ß) and pro-thrombotic factors (aberrations in the thrombin-antithrombin complex)(1) which have been documented in the IPH and POEMS syndrome, may contribute to a possible association between these entities. Although the association between these two entities is yet to be confirmed, the authors present this case in order to contribute to its elucidation.
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http://dx.doi.org/10.17235/reed.2017.4623/2016DOI Listing
May 2017

A New Paradigm in Gallstones Diseases and Marked Elevation of Transaminases: An Observational Study.

Ann Hepatol 2017 March-April;16(2):285-290

Internal Medicine department, Centro Hospitalar e Universitário de Coimbra (CHUC).

Background: In clinical practice, it is assumed that a severe rise in transaminases is caused by ischemic, viral or toxic hepatitis. Nevertheless, cases of biliary obstruction have increasingly been associated with significant hypertransaminemia. With this study, we sought to determine the true etiology of marked rise in transaminases levels, in the context of an emergency department.

Material And Methods: We retrospectively identified all patients admitted to the emergency unit at Centro Hospitalar e Universitário de Coimbra between 1st January 2010 and 31st December 2010, displaying an increase of at least one of the transaminases by more than 15 times. All patient records were analyzed in order to determine the cause of hypertransaminemia.

Results: We analyzed 273 patients - 146 males, mean age 65.1 ± 19.4 years. The most frequently etiology found for marked hypertransaminemia was pancreaticobiliary acute disease (n = 142;39.4%), mostly lithiasic (n = 113;79.6%), followed by malignancy (n = 74;20.6%), ischemic hepatitis (n = 61;17.0%), acute primary hepatocellular disease (n = 50;13.9%) and muscle damage (n = 23;6.4%). We were not able to determine a diagnosis for 10 cases. There were 27 cases of recurrence in the lithiasic pancreaticobiliary pathology group. Recurrence was more frequent in the group of patients who had not been submitted to early cholecystectomy after the first episode of biliary obstruction (p = 0.014). The etiology of hypertransaminemia varied according to age, cholestasis and glutamic-pyruvic transaminase values.

Conclusion: Pancreaticobiliary lithiasis is the main cause of marked hypertransaminemia. Hence, it must be considered when dealing with such situations. Not performing cholecystectomy early on, after the first episode of biliary obstruction, may lead to recurrence.
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http://dx.doi.org/10.5604/16652681.1231588DOI Listing
April 2017

A Scary Onset of a Rare and Aggressive Type of Primary Breast Sarcoma: A Case Report.

Case Rep Oncol 2016 Sep-Dec;9(3):796-801. Epub 2016 Nov 25.

Gynecology A Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

Primary breast sarcoma, arising from connective tissue within the breast, is extremely rare, accounting for less than 1% of all primary breast malignancies and no more than 5% of all sarcomas. The rarity of this pathology limits most studies to case reports and small retrospective studies, which has led to a lack of consensus on the clinical management. We report a clinical case of a 52-year-old woman, perimenopausal, previously healthy, with regular breast surveillance, who presented with a large (>20 cm) and rapidly expanding hypervascularized tumor of the left breast developed over 10 days, with a very thin preulcerative skin over the last 4 days. There was no systemic dissemination. The patient was submitted to total mastectomy and excision of axillary adenopathy. The tumor was diagnosed histologically as malignant phyllodes tumor associated with areas of high-grade sarcoma. Due to rapid growth and aggressive histological characteristics, adjuvant chemotherapy and radiotherapy were performed. There is a lot of evidence that tumors larger than 5 cm are associated with a poor prognosis. Despite the poor prognosis associated with this aggressive entity, the patient had no recurrence during 5 years of follow-up. We review the relevant literature about primary breast sarcomas.
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http://dx.doi.org/10.1159/000452946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216215PMC
November 2016

Effect of a pH Gradient on the Protonation States of Cytochrome c Oxidase: A Continuum Electrostatics Study.

J Chem Inf Model 2017 02 31;57(2):256-266. Epub 2017 Jan 31.

Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa , 2781-901 Oeiras, Portugal.

Cytochrome c oxidase (CcO) couples the reduction of dioxygen to water with transmembrane proton pumping, which leads to the generation of an electrochemical gradient. In this study we analyze how one of the components of the electrochemical gradient, the difference in pH across the membrane, or ΔpH, influences the protonation states of residues in CcO. We modified our continuum electrostatics/Monte Carlo (CE/MC) method in order to include the ΔpH and applied it to the study of CcO, in what is, to our best knowledge, the first CE/MC study of CcO in the presence of a pH gradient. The inclusion of a transmembrane pH gradient allows for the identification of residues whose titration behavior depends on the pH on both sides of the membrane. Among the several residues with unusual titration profiles, three are well-known key residues in the proton transfer process of CcO: E286, Y288, and K362. All three residues have been previously identified as being critical for the catalytic or proton pumping functions of CcO. Our results suggest that when the pH gradient increases, these residues may be part of a regulatory mechanism to stem the proton flow.
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http://dx.doi.org/10.1021/acs.jcim.6b00575DOI Listing
February 2017

Cytomegalovirus, inflammatory bowel disease, and anti-TNFα.

Int J Colorectal Dis 2017 May 13;32(5):645-650. Epub 2017 Jan 13.

Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Praçeta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.

Background And Purpose: Anti-TNFα agents emerged in inflammatory bowel disease (IBD) as an effective option in situations that, otherwise, would be refractory to medical therapy. Cytomegalovirus infection may present with a high spectrum of manifestations and lead to high morbidity and mortality. However, its clinical significance in IBD course remains unknown and data on its association with anti-TNFα are limited.

Aims: This study aims to evaluate cytomegalovirus (CMV) infection/disease in patients with IBD treated with anti-TNFα; if possible, possible risk factors associated with CMV infection/disease in IBD patients under anti-TNFα as well as the influence of CMV infection/disease in IBD course would be determined.

Methods: During three consecutive years, all IBD patients starting infliximab in our department were included. Cytomegalovirus status before anti-TNFα was evaluated. Data regarding IBD, therapeutic and IBD course after infliximab, were recorded. CMV analysis was performed with polymerase chain reaction (PCR)-cytomegalovirus in peripheral blood and colonoscopy with biopsies (histopathology/immunohistochemistry).

Results: We included 29 patients: female-83%; Crohn's disease-51.8%, ulcerative colitis-44.8%, non-classified colitis-3.4%; 23 cytomegalovirus seropositive. Median follow-up: 19 months (3-36). During follow-up, 14 patients were under combination therapy with azathioprine and 5 did at least 1 cycle of corticosteroids. Twenty-one patients responded to infliximab. We registered 8 exacerbations of IBD. Four patients discontinued infliximab: none had CMV infection. We documented 1 case of intestinal cytomegalovirus infection-detected in biopsies performed per protocol in an asymptomatic UC patient, who responded to valganciclovir without infliximab discontinuation.

Conclusions: Infliximab, with/without immunosuppression, does not confer an increased risk of (re)activation of cytomegalovirus. Cytomegalovirus was not responsible neither for significant morbidity nor mortality in IBD.
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http://dx.doi.org/10.1007/s00384-017-2752-5DOI Listing
May 2017
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