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Does SARS‐Cov‐2 invade the brain? Translational lessons from animal models
Get PDFThe current coronavirus disease (COVID-19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised the possibility of potential neurotropic properties of this virus. Indeed, neurological sequelae of SARS-CoV-2 infection have already been reported and highlight the relevance of considering the neurological impact of coronavirus (CoV) from a translational perspective. Animal models of SARS and Middle East respiratory syndrome, caused by structurally similar CoVs during the 2002 and 2012 epidemics, have provided valuable data on nervous system involvement by CoVs and the potential for central nervous system spread of SARS-CoV-2. One key finding that may unify these pathogens is that all require angiotensin-converting enzyme 2 as a cell entry receptor. The CoV spike glycoprotein, by which SARS-CoV-2 binds to cell membranes, binds angiotensin-converting enzyme 2 with a higher affinity compared with SARS-CoV. The expression of this receptor in neurons and endothelial cells hints that SARS-CoV-2 may have higher neuroinvasive potential compared with previous CoVs. However, it remains to be determined how such invasiveness might contribute to respiratory failure or cause direct neurological damage. Both direct and indirect mechanisms may be of relevance. Clinical heterogeneity potentially driven by differential host immune-mediated responses will require extensive investigation. Development of disease models to anticipate emerging neurological complications and to explore mechanisms of direct or immune-mediated pathogenicity in the short and medium term is therefore of great importance. In this brief review, we describe the current knowledge from models of previous CoV infections and discuss their potential relevance to COVID-19.info:eu-repo/semantics/publishedVersio
Bowel anastomosis leakage following endometriosis surgery: an evidence based analysis of risk factors and prevention techniques
Get PDFBackground: Deep endometriosis most commonly involves the rectosigmoid junction and its management often requires a colorectal resection. Anastomotic leakage is a severe complication after resection and affects 1-6% of the cases.
Objective: To evaluate the risk factors related to anastomotic leakage following endometriosis sur-gery, its prevention techniques and the role of protective stomas.
Methods: A comprehensive literature review was carried out for English-language publications in Pubmed and Google Scholar. We included all studies including the following MeSH terms and key words: Anastomotic leakage AND bowel surgery OR Endometriosis OR Colorectal surgery OR Bowel endometriosis. Two authors independently made a selection and analysed relevant abstracts according to the aim of this review.
Results: Risk factors and preventive measures were categorised considering the patient condition, the intra- operative setting and the surgical procedure itself. Level I and II recommendations include modifiable risk factors such as the use of stapled or handsewn anastomosis; intra-operative air leak test to check the integrity of the anastomosis; systematic use of pelvic and trans-anal drainage; application of protective or ghost ileostomy in low rectal resections; vaginal closure before the bowel resection; use of oral antibiotics the day before surgery and performing partial mesorectal resection near the bowel wall. Diverting stomas may decrease the morbidity and the clinical consequences of leakage over 65% of low rectal resections but may cause significant adverse effects.
Conclusion: Evidence-based protective actions are crucial to reduce clinical consequences of anastomotic leakage and to minimise the use of protective stomas in endometriosis surgery.info:eu-repo/semantics/publishedVersio
Real-world retrospective comparison of 0.19 mg fluocinolone acetonide and 0.7 mg dexamethasone intravitreal implants for the treatment of diabetic macular edema in vitrectomized eyes
Get PDFPurpose: The aim of this study was to evaluate the long-term real-world effectiveness of FAc and DEX implants in vitrectomized DME eyes in a real-world setting.
Methods: This was a non-interventional, retrospective, comparative study of 46 vitrectomized eyes in 33 patients with persistent or recurrent DME quantified best-corrected visual acuity (BCVA), central foveal thickness (CFT) and intraocular pressure (IOP) over up to 37 months.
Results: Both FAc and DEX treatment led to statistically and clinically significant improvements in BCVA and CFT. FAc >10-letter improvement on the Early Treatment Diabetic Retinopathy Study [ETDRS] chart over months 3-24 and a sustained ~200 µm CFT reduction over months 1-24; DEX: >5-letter improvement on the ETDRS chart at months 1 and 3 and >100 µm CFT reduction at month 1. FAc demonstrated sustained, stable and predictable effects on BCVA and CFT over 24 months and also improved BCVA and decreased CFT in a cohort of DME eyes that was refractory to DEX over 6 months.
Conclusion: This real-world study demonstrates long-term effectiveness of FAc in vitrectomized DME eyes and sustained effectiveness in DME eyes that did not respond to DEX therapy.Writing support was provided by Hayward Medical Communications and funded by Alimera Sciences Ltd.
This paper was funded by Alimera Sciences Ltd.info:eu-repo/semantics/publishedVersio
Gastric peroral endoscopic myotomy for transthyretin amyloidosis gastroparesis
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Gastroenteropancreatic Neuroendocrine Neoplasia Characterization in Portugal: Results from the NETs Study Group of the Portuguese Society of Endocrinology, Diabetes and Metabolism
Get PDFBackground: The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) has been increasing in the last five decades, but there is no large-scale data regarding these tumours in Portugal. We conducted a cross-sectional, multicentric study in main Portuguese centers to evaluate the clinical, pathological, and therapeutic profile of GEP-NENs.
Methods: From November, 2012, to July, 2014, data from 293 patients diagnosed with GEP-NENs from 15 centers in Portugal was collected and registered in an online electronic platform.
Results: Median age at diagnosis was 56.5 (range: 15-87) years with a preponderance of females (54.6%). The most frequent primary sites were the pancreas (31.1%), jejunum-ileum (24.2%), stomach (13.7%), and rectum (8.5%). Data regarding hormonal status was not available in most patients (82.3%). Stratified by the tumour grade (WHO 2010 classification), we observed 64.0% of NET G1, 24.7% of NET G2, and 11.3% of NEC. Poorly differentiated tumours occurred mainly in older patients (p = 0.017), were larger (p < 0.001), and presented more vascular (p = 0.004) and lymphatic (p = 0.001) invasion. At the time of diagnosis, 44.4% of GEP-NENs presented metastatic disease. Surgery (79.6%) and somatostatin analogues (30.7%) were the most frequently used therapies of GEP-NENs with reported grading.
Conclusion: In general, Portuguese patients with GEP-NENs presented similar characteristics to other populations described in the literature. This cross-sectional study represents the first step to establish a national database of GEP-NENs that may aid in understanding the clinical and epidemiological features of these tumours in Portugal.
Methods: From November, 2012, to July, 2014, data from 293 patients diagnosed with GEP-NENs from 15 centers in Portugal was collected and registered in an online electronic platform.
Results: Median age at diagnosis was 56.5 (range: 15-87) years with a preponderance of females (54.6%). The most frequent primary sites were the pancreas (31.1%), jejunum-ileum (24.2%), stomach (13.7%), and rectum (8.5%). Data regarding hormonal status was not available in most patients (82.3%). Stratified by the tumour grade (WHO 2010 classification), we observed 64.0% of NET G1, 24.7% of NET G2, and 11.3% of NEC. Poorly differentiated tumours occurred mainly in older patients (p = 0.017), were larger (p < 0.001), and presented more vascular (p = 0.004) and lymphatic (p = 0.001) invasion. At the time of diagnosis, 44.4% of GEP-NENs presented metastatic disease. Surgery (79.6%) and somatostatin analogues (30.7%) were the most frequently used therapies of GEP-NENs with reported grading.
Conclusion: In general, Portuguese patients with GEP-NENs presented similar characteristics to other populations described in the literature. This cross-sectional study represents the first step to establish a national database of GEP-NENs that may aid in understanding the clinical and epidemiological features of these tumours in Portugal.This study was industry-sponsored by the pharmaceutical company Ipsen Portugal. João Vinagre (CEECIND/00201/2017) and Paula Soares receive funding from the Operational Program for Competitiveness and Internationalization (POCI), Portugal 2020; Portuguese funds through FCT (Fundação para a Ciência e a Tecnologia)/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) and the project “Advancing Cancer Research: From Basic Knowledge to Application” (NORTE-01-0145-FEDER-000029); and “Projetos Estruturados de I&D&I,” funded by Norte 2020—Programa Operacional Regional do Norte. Further funding was from the European Regional Development Fund (ERDF) through the Operational Program for Competitiveness and Internationalization (COMPETE 2020) and Portuguese national funds via FCT (Fundação para a Ciência e a Tecnologia), under the project “POCI-01-0145-FEDER-016390: CANCEL STEM.” Maria João Bugalho and João Vinagre were funded by the Sociedade Portuguesa de Endocrinologia, Diabetes e Metabolismo through the Study Group for Neuroendocrine Tumours.info:eu-repo/semantics/publishedVersio
Non-AIDS-related comorbidities in people living with HIV-1 aged 50 years and older: The AGING POSITIVE study
Get PDFObjective: To characterize the profile of non-AIDS-related comorbidities (NARC) in the older HIV-1-infected population and to explore the factors associated with multiple NARC.
Methods: This was a multicentre, cross-sectional study including HIV-1-infected patients aged ≥50 years, who were virologically suppressed and had been on a stable antiretroviral therapy (ART) regimen for at least 6 months. A multiple regression model explored the association between demographic and clinical variables and the number of NARC.
Results: Overall, 401 patients were enrolled. The mean age of the patients was 59.3 years and 72.6% were male. The mean duration of HIV-1 infection was 12.0 years and the median exposure to ART was 10.0 years. The mean number of NARC was 2.1, and 34.7% of patients had three or more NARC. Hypercholesterolemia was the most frequent NARC (60.8%), followed by arterial hypertension (39.7%) and chronic depression/anxiety (23.9%). Arterial hypertension and diabetes mellitus were the most frequently treated NARC (95.6% and 92.6% of cases, respectively). The linear regression analysis showed a positive relationship between age and NARC (B=0.032, 95% confidence interval 0.015-0.049; p=0.0003) and between the duration of HIV-1 infection and NARC (B=0.039, 95% confidence interval 0.017-0.059; p=0.0005).
Conclusions: A high prevalence of NARC was found, the most common being metabolic, cardiovascular, and psychological conditions. NARC rates were similar to those reported for the general population, suggesting a larger societal problem beyond HIV infection. A multidisciplinary approach is essential to reduce the burden of complex multi-morbid conditions in the HIV-1-infected population.Merck Sharp & Dohme, Lda, Portugal provided financial support for the non-interventional study (Protocol Nr. MK0518-826 ).info:eu-repo/semantics/publishedVersio
A pair of peptides inhibits seeding of the hormone transporter transthyretin into amyloid fibrils
Get PDFThe tetrameric protein transthyretin is a transporter of retinol and thyroxine in blood, cerebrospinal fluid, and the eye, and is secreted by the liver, choroid plexus, and retinal epithelium, respectively. Systemic amyloid deposition of aggregated transthyretin causes hereditary and sporadic amyloidoses. A common treatment of patients with hereditary transthyretin amyloidosis is liver transplantation. However, this procedure, which replaces the patient's variant transthyretin with the WT protein, can fail to stop subsequent cardiac deposition, ultimately requiring heart transplantation. We recently showed that preformed amyloid fibrils present in the heart at the time of surgery can template or seed further amyloid aggregation of native transthyretin. Here we assess possible interventions to halt this seeding, using biochemical and EM assays. We found that chemical or mutational stabilization of the transthyretin tetramer does not hinder amyloid seeding. In contrast, binding of the peptide inhibitor TabFH2 to ex vivo fibrils efficiently inhibits amyloid seeding by impeding self-association of the amyloid-driving strands F and H in a tissue-independent manner. Our findings point to inhibition of amyloid seeding by peptide inhibitors as a potential therapeutic approach.This work was supported by Amyloidosis Foundation Grant 20160759 and 20170827, National Institutes of Health Grant R01-AG048120, and The Howard Hughes Medical Institute. The authors and UCLA have filed an international patent application for the TTR inhibitors (number PCT/US17/40103). D. S. E. is an advisor and equity holder of ADRx, Inc. L. S. is a consultant of ADRx, Inc. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.info:eu-repo/semantics/publishedVersio
Avaliac ̧ão do tempo de atraso do índice bispectral naresposta à indução da anestesia: estudo observacional
Get PDFBackground and objectives: According to the manufacturer, the Bispectral Index (BIS) has a processing time delay of 5-10s. Studies addressing this have suggested longer delays. We evaluated the time delay in the Bispectral Index response.
Methods: Based on clinical data from 45 patients, using the difference between the predicted and the real BIS, calculated during a fixed 3minutes period after the moment the Bispectral Index dropped below 80 during the induction of general anesthesia with propofol and remifentanil.
Results: The difference between the predicted and the real BIS was in average 30.09±18.73s.
Conclusion: Our results may be another indication that the delay in BIS processing may be much longer than stated by the manufacture, a fact with clinical implications.info:eu-repo/semantics/publishedVersio
Frailty in cardiovascular disease: Screening tools
Get PDFCardiovascular disease (CVD) is the leading cause of death in developed countries and disproportionately affects older adults. Frailty is a complex clinical syndrome with multiple causes and contributing factors in which there is increased vulnerability when exposed to a minor stressor and increased risk for adverse outcomes, such as disability, hospitalization and mortality. Frailty is an important prognostic factor in patients with CVD, and so identifying this feature when assessing these patients may help to individually tailor cardiovascular treatment. The first step is to identify frailty. Several tools have been validated as screening methods for frailty. However, they diverge with regard to complexity, nature, feasibility and the outcome they can predict. The aim of this review is to describe the available screening tools for frailty and to examine their usefulness in patients with CVD.info:eu-repo/semantics/publishedVersio
Orbital solitary fibrous tumor: A painless mass after a dacryochystorhinostomy
Get PDFThe solitary fibrous tumor (STF) is a rare spindle cell tumor that most often occurs in the pleura, mediastinum and other serosal sites, but it can be found anywhere. The authors present a case report of a 35-year-old male who was submitted to an eventless left external dacryocystorhinostomy (DCR) due to epiphora. During the surgery no tumors or anomalous tissues were visualized. Five months later the patient presented a painless mass at the lower medial quadrant of the left orbit, near the lacrimal fossa. A computed tomography, a magnetic resonance imaging and an orbital ultrasound were performed. A round, very vascularized and highly contrast enhanced mass was found. An anterior orbitotomy was done. Histological aspects and immunohistochemical markers were consistent with STF. The tumor was not visualized during the DCR. The authors think that the growth of the tumor and the weakening of the tissues in the medial canthus after the DCR allowed the tumor to move anteriorly within the orbit.info:eu-repo/semantics/publishedVersio