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Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

AbstractThe goal of this paper is to provide updated diagnostic criteria for the epilepsy syndromes that have a variable age of onset, based on expert consensus of the International League Against Epilepsy Nosology and Definitions Taskforce (2017–2021). We use language consistent with current accepted epilepsy and seizure classifications and incorporate knowledge from advances in genetics, electroencephalography, and imaging. Our aim in delineating the epilepsy syndromes that present at a variable age is to aid diagnosis and to guide investigations for etiology and treatments for these patients.

ABSTRACT Eighty-four cerebrospinal fluid (CSF) samples from different children who presented with signs and symptoms of meningitis were evaluated for the presence of Mycobacterium tuberculosis complex organisms by the Gen-Probe Amplified Mycobacterium tuberculosis Direct Test (MTD; Gen-Probe, San Diego, Calif.). All CSF samples had negative acid-fast smears by the Ziehl-Neelsen staining method. M. tuberculosis was recovered from five samples. M. tuberculosis did not grow from 19 additional samples, but the samples were from patients who fulfilled specific clinical and laboratory criteria for probable tuberculous meningitis (TBM). The remaining samples ( n = 60) were from patients with other infections or noninfectious causes of meningitis. The results of the MTD were interpreted as positive or negative on the basis of recommended cutoff values for respiratory specimens. These results were interpreted as true or false positives or true or false negatives on the basis of the results of M. tuberculosis culture or whether the patient fulfilled criteria for probable TBM. The Gen-Probe MTD was 33% sensitive and 100% specific for detecting M. tuberculosis complex organisms in these 84 CSF samples. If the cutoff values for positive results were decreased for the MTD (≥11,000 versus ≥30,000 relative light units), the sensitivity increased to 83% and the specificity remained 100%. These results for the MTD are encouraging considering that TBM is a highly fatal disease and difficult to diagnose by conventional laboratory techniques.

Abstract Introduction: The immunoglobulin (Ig) is one of the most diverse molecules in nature, and its therapeutic potential, by stimulation of the immune system, has been widely studied/used. Its effect is manifest at the cellular and humoral compartments. However it is still to clarify the specific effect of each fraction of the molecule in the observed immune stimulation. Aims: To develop a murine model of ASCT that mimics the autologous transplant in humans To study the independent effect of the various fractions of the immunoglobulin in the reconstitution of the immune system after ASCT. Methods: In this study, we developed, de novo, a murine model of ASCT. Four groups of transplanted animals were established (weekly injections of: Ig (n=8) or Fab fragment (n=7) or Fc fragment (n=6) or saline (control, n=7)). The evolution of the immune reconstitution was monitored weekly and compared among groups by characterization of cellular fractions by flow cytometry, serum levels of Igs by ELISA and thymic function by quantification of TRECs (“T cell receptor excision circles”). The statistical analysis of the longitudinal data was performed by a linear-mixed effects model. Results: We determined that a regimen of daily injections of G-CSF for 4 consecutive days produces a degree of mobilization of hematopoietic stem cells adequate for a donors/recipient ratio of 9 to 7, and to a standard engraftment extent. Regarding the recovery of cellular sub-populations among groups, the major differences occur up to the 6th week (w) after ASCT. As soon as 2 w after ASCT the treated groups show higher counts of CD4+ T cells compared with control mice (p<0.05). The maximum number of CD4+ T lymphocytes was attained at 2 w after ASCT for mice treated with Fab and Fc and at 9 w for mice treated with polyclonal Ig and PBS. The recovery of CD4+ T lymphocytes in the treated groups was higher compared to control (p<0.001 for Fab, p<0.001 for Fc and p=0.001 for polyclonal Ig). For CD8+ T cells, the mice treated with Fc show, during all the follow up, superior values, being statistically significant when compared to PBS treated mice (p=0.003). The differences with the other groups vary with time. Regarding the recovery of CD19+ lymphocytes, the mice treated with Fab reveal, after the 7th w, superior counts compared to all the other groups (p<0.05). Treated groups (Fab and Fc) show higher values of serum IgM compared to control, as well as an earlier recovery of levels (p<0.05). In what concerns CD4+ naïve T cells, the group treated with polyclonal Ig shows an increased recovery during the first weeks of treatment compared with the other groups (p<0.05). Conclusions and Discussion: The early treatment with polyclonal Ig or its fragments is highly beneficial for the recovery of CD4 and CD8 T lymphocytes (earlier recovery and higher cell counts). After the 6th week after transplant there is a tendency for homeostasis. The increase of CD4+ naïve T cells with Ig treatment may well correspond to an increased thymopoiesis, as suggested by our previous studies.

AbstractObjectiveDescribe a reliable anatomical landmark that can be used to locate the maxillary sinus natural ostium (MSNO) during endoscopic surgery, even if the uncinate process is preserved.DesignDescriptive anatomical.SettingAn anatomical and radiological study was performed to evaluate the consistency of the landmark, denominated "M" line.Subjects and MethodsDissections were performed in 57 cadaver heads (114 sides). In addition, 73 computerised tomography (CT) scans (146 sides) of patients with chronic inflammatory sinonasal disease were analysed using a three‐dimensional (3D) reconstruction computer program.ResultsThe "M" line crossed the MSNO in 112 dissected sides (98.2%) and 140 sides at CT 3D reconstruction (95.9%).ConclusionThe "M" line is a reliable anatomical landmark for predicting MSNO location. As such, it could improve and facilitate endoscopic sinus surgery, using traditional, minimally invasive or uncinate preserving techniques.