Artrodesis circunferencial: Plif más tornillos translaminofacetarios

OBJETIVO: Evaluar el resultado clínico y radiológico de 10 pacientes operados por patología degenerativa lumbar, en los que se les realizó artrodesis intersomática con injerto óseo tricortical de cresta ilíaca y artrodesis posterolateral instrumentada con tornillos translaminofacetarios. MÉTODOS: Se evaluaron 10 pacientes, 4 hombres y 6 mujeres operados por el mismo cirujano entre junio de 2006 y diciembre de 2007. RESULTADOS: Se obtuvo un significativo descenso de la discapacidad y del dolor (según las escalas de Oswestry y la escala visual analógica), obteniéndose una tasa de fusión del 100% al año de seguimiento. CONCLUSIONES: Los resultados clínicos y radiológicos de este estudio establecen a éste procedimiento como confiable, de bajo costo y baja morbilidad, con una alta tasa de fusión y buenos resultados clínicos

Unique pharmacological properties of serotoninergic G-protein coupled receptors from cestodes.

BACKGROUND:Cestodes are a diverse group of parasites, some of them being agents of neglected diseases. In cestodes, little is known about the functional properties of G protein coupled receptors (GPCRs) which have proved to be highly druggable targets in other organisms. Notably, serotoninergic G-protein coupled receptors (5-HT GPCRs) play major roles in key functions like movement, development and reproduction in parasites. METHODOLOGY/PRINCIPAL FINDINGS:Three 5-HT GPCRs from Echinococcus granulosus and Mesocestoides corti were cloned, sequenced, bioinformatically analyzed and functionally characterized. Multiple sequence alignment with other GPCRs showed the presence of seven transmembrane segments and conserved motifs but interesting differences were also observed. Phylogenetic analysis grouped these new sequences within the 5-HT7 clade of GPCRs. Molecular modeling showed a striking resemblance in the spatial localization of key residues with their mammalian counterparts. Expression analysis using available RNAseq data showed that both E. granulosus sequences are expressed in larval and adult stages. Localization studies performed in E. granulosus larvae with a fluorescent probe produced a punctiform pattern concentrated in suckers. E. granulosus and M. corti larvae showed an increase in motility in response to serotonin. Heterologous expression revealed elevated levels of cAMP production in response to 5-HT and two of the GPCRs showed extremely high sensitivity to 5-HT (picomolar range). While each of these GPCRs was activated by 5-HT, they exhibit distinct pharmacological properties (5-HT sensitivity, differential responsiveness to ligands). CONCLUSIONS/SIGNIFICANCE:These data provide the first functional report of GPCRs in parasitic cestodes. The serotoninergic GPCRs characterized here may represent novel druggable targets for antiparasitic intervention

Protoscoleces of <i>Echinococcus granulosus</i> stained with the fluorescent probe UCM120 under the confocal scanning laser microscope and effect of the parent compound UCM2550 on the motility.

<p><b>-</b> Protoscoleces were fixed, after washing they were incubated in the presence of the probe (100 μM) during several days, washed, fixed, washed again, mounted, and then observed by confocal microscopy. (A) Structure of the fluorescent probe UCM120 with the structure of the parent compound UCM2550 shown in black and the dansyl group shown in light brown. Images of two protoscoleces obtained from superficial (B) or from an entire stack of laser scanning (C). To assess specificity, protoscoleces were labeled under the same conditions with the probe (100 μM) in the presence of an excess (1000 μM) of 5-HT and the image projection was obtained from an entire stack of pictures (D). Relative motility observed in the presence of increasing concentrations of the parent compound UCM2550 in the WMicrotracker device measured after two hours of incubation (E); Image based motility quantification measured as a pixel change (F). Further details are provided in the Methods section. Asterisks indicate treatments found to be significantly different from the controls (*P ≤ 0.05) with t-test (E) or ANOVA and Dunnet post comparison tests (****P ≤ 0.0001, F). R: rostellum; S: suckers and Bo: body. The scale bar represents 50 μm in (A), (B) and (C) and 100 μm in (D). Arrowheads indicate localization of the probe.</p

Molecular modeling of serotoninergic receptors from cestodes.

<p>The structural similarities between three cestode receptors and the published structure of the serotoninergic receptor from human (4IAR) are shown. A) Model of the serotonin receptor 5-HT_7Egran1 (Brown) superposed to the published structure of the human serotonin receptor 5-HT1B (blue). B) Close view of the putative ergotamine interaction with residues of the transmembrane domains III and V from 5-HT_7Egran1 (lateral chains of the amino acids involved are indicated in red), molecular distances between atoms are indicated. C) Model of 5-HT_7Egran2 (violet) superposed to 5-HT1B (blue). D) Close view of the ergotamine interaction with some residues of the transmembrane domains III and V from 5-HT7_Egran2. E) Model of 5-HT_7Mco1 (Brown) superposed to 5-HT1B (blue). F) Close view of the ergotamine interaction with some residues of the transmembrane domains III and V from 5-HT_7Mco1. In all the representations, the molecule of ergotamine was marked in green and the residues in transmembrane domains potentially involved in ergotamine interaction were marked in red.</p

Heterologous expression of GPCRs reveals 5-HT evoked cAMP accumulation.

<p>Time resolved measurements of cAMP accumulation in cells expressing individual cestode serotoninergic GPCRs (A) 5-HT_7Egran1, (B) 5-HT_7Egran2 and (C) 5-HT_7Mco1 before and after addition of IBMX (1^st arrow, 200μM) and different doses of 5-HT (2^nd arrow, doses indicated in legend). (D, E & F) dose response relationships to 5-HT measuring peak amplitude of 5-HT evoked luminescence change in cells expressing the indicated GPCR (solid circles), or untransfected HEK-293 cells (open circles).</p

Cladogram of cestode and invertebrate serotoninergic GPCRs.

<p>The amino acid sequences of predicted cestode serotonin receptors were aligned with the repertoire of serotonin receptors cloned from various other flatworm and non-flatworm invertebrate model organisms; <i>Dugesia japonica</i>, 5-HT_Dj; <i>Schistosoma mansoni</i>, 5-HT_Sm; <i>Caenorhabditis elegans</i>, 5-HT_Ce; <i>Drosophila melanogaster</i>, 5-HT_Dm. The cestode GPCR sequences cloned and functionally expressed in this study (5-HT_7Egran1, 5-HT_7Egran2, 5-HT_7Mco1) cluster within a clade of 5-HT7 like receptors (green), as does an additional predicted <i>M</i>. <i>corti</i> sequence (5-HT_7Mco2). Other predicted cestode serotoninergic sequences (5-HT_1Egran1 and 5-HT_1Egran2) cluster within a clade of 5-HT1 like receptors (blue). See <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006267#sec005" target="_blank">methods</a> for complete list of UniProt and GenBank sequence identifiers used in this analysis. Analysis was bootstrapped with 500 replicates.</p

Does the Use of Immunosuppressive Drugs Impact on SARS-CoV-2 Infection Outcome? Data From A National Cohort of Patients With Immune-Mediated Inflammatory Diseases (SAR-COVID Registry)

Background/objectiveThis study describes the impact of immunomodulatory and/or immunosuppressive (IM/IS) drugs in the outcomes of COVID-19 infection in a cohort of patients with immune-mediated inflammatory diseases (IMIDs).MethodsAdult patients with IMIDs with a confirmed SARS-CoV-2 infection were included. Data were reported by the treating physician between August 13, 2020 and July 31, 2021. Sociodemographic data, comorbidities, and DMARDs, as well as clinical characteristics, complications, and treatment of the SARS-CoV-2 infection, were recorded. Descriptive analysis and multivariable logistic regression models were carried out.ResultsA total of 1672 patients with IMIDs were included, of whom 1402 were treated with IM/IS drugs. The most frequent diseases were rheumatoid arthritis (47.7%) and systemic lupus erythematosus (18.4%). COVID-19 symptoms were present in 95.2% of the patients. A total of 461 (27.6%) patients were hospitalized, 8.2% were admitted to the intensive care unit, and 4.4% died due to COVID-19.Patients without IM/IS treatment used glucocorticoids less frequently but at higher doses, had higher levels of disease activity, were significantly older, were more frequently hospitalized, admitted to the intensive care unit, and died due to COVID-19. After adjusting for these factors, treatment with IM/IS drugs was not associated with a worse COVID-19 outcome (World Health Organization-Ordinal Scale ≥5) (odds ratio, 1.24; 95% confidence interval, 0.73-2.06).ConclusionsSAR-COVID is the first multicenter Argentine registry collecting data from patients with rheumatic diseases and SARS-CoV-2 infection. After adjusting for relevant covariates, treatment with IM/IS drugs was not associated with severe COVID-19 in patients with IMIDs.Study registrationThis study has been registered in ClinicalTrials.gov under the number NCT04568421

Global attitudes in the management of acute appendicitis during COVID-19 pandemic: ACIE Appy Study

Background: Surgical strategies are being adapted to face the COVID-19 pandemic. Recommendations on the management of acute appendicitis have been based on expert opinion, but very little evidence is available. This study addressed that dearth with a snapshot of worldwide approaches to appendicitis. Methods: The Association of Italian Surgeons in Europe designed an online survey to assess the current attitude of surgeons globally regarding the management of patients with acute appendicitis during the pandemic. Questions were divided into baseline information, hospital organization and screening, personal protective equipment, management and surgical approach, and patient presentation before versus during the pandemic. Results: Of 744 answers, 709 (from 66 countries) were complete and were included in the analysis. Most hospitals were treating both patients with and those without COVID. There was variation in screening indications and modality used, with chest X-ray plus molecular testing (PCR) being the commonest (19\ub78 per cent). Conservative management of complicated and uncomplicated appendicitis was used by 6\ub76 and 2\ub74 per cent respectively before, but 23\ub77 and 5\ub73 per cent, during the pandemic (both P < 0\ub7001). One-third changed their approach from laparoscopic to open surgery owing to the popular (but evidence-lacking) advice from expert groups during the initial phase of the pandemic. No agreement on how to filter surgical smoke plume during laparoscopy was identified. There was an overall reduction in the number of patients admitted with appendicitis and one-third felt that patients who did present had more severe appendicitis than they usually observe. Conclusion: Conservative management of mild appendicitis has been possible during the pandemic. The fact that some surgeons switched to open appendicectomy may reflect the poor guidelines that emanated in the early phase of SARS-CoV-2